CTPC - Atrophic Thyroiditis and TSHR antibody
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Atrophic ThyroiditisGraves, euthyroid, Hypo-hyper1Christy, James H.; Morse, Richard S.1977Hypothyroid Graves' disease
Graves' disease has recently been shown to exist in a euthyroid form in untreated patients. Sporadic reports of a hypothyroid form are beginning to emerge, thus illustrating the multlfaceted nature of this disorder, with thyrotoxicosis at one end of the spectrum and hypothyroidism at the other.
Three patients with nonthyrotoxic Graves' disease and concomitant hypothyroidism were seen at Emory University Hospital in one year, and detailed studies were made to help elucidate the nature of this unusual combination. Results of these studies are reported and briefly discussed.
It is suggested that, until more is known about this intriguing aspect of the Graves' disease spectrum, the label “hypothyroid Graves' disease” is justifiable.
The American Journal of Medicine262291-29610.1016/0002-9343(77)90325-4http://www.sciencedirect.com/science/article/pii/0002934377903254Case studies of 3 patients, justification for using the term "hypothyroid Graves"
AntibodiesHypothyroidism, euthyroidism, Hashimoto's, IGG, TSH, goiter1Chiovato, L.; Vitti, P.; Santini, F.; Lopez, G.; Mammoli, C.; Bassi, P.; Giusti, L.; Tonacchera, M.; Fenzi, G.; Pinchera, A.1990Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis
Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established.
To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5).
Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005).
The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.
The Journal of Clinical Endocrinology and Metabolism17140-4510.1210/jcem-71-1-40Indirect evidence that TSH receptor blocking antibody causes atrophic thyroiditis, in that it is mainly found in AT patients.
Hyper-HypoTBAb, hypothyroidism, euthyroidism, 11 years, T4 therapy, remission, Hashimoto's, goiter1Takasu, Nobuyuki; Yamada, Takashi; Takasu, Mika; Komiya, Ichiro1992Disappearance of thyrotropin-blocking antibodies and spontaneous recovery from hypothyroidism in autoimmune thyroiditis
BACKGROUND: Hypothyroidism may result from the production of antibodies that block the actions of thyrotropin. How often these thyrotropin-blocking antibodies are a cause of hypothyroidism and whether their production may cease, causing hypothyroidism to disappear, have not been extensively studied.
METHODS: We determined the frequency with which thyrotropin-blocking antibodies were present in 172 hypothyroid patients with goitrous autoimmune thyroiditis (Hashimoto's disease) and 64 hypothyroid patients with atrophic autoimmune thyroiditis (idiopathic primary hypothyroidism). For 6 to 11 years we then followed 21 of these patients who were found to have thyrotropin-blocking antibodies. They received levothyroxine therapy for 3.5 to 8 years, after which it was discontinued. At frequent intervals during this time we measured the patients' serum concentrations of thyroxine, triiodothyronine, thyrotropin, and thyrotropin-blocking antibodies (measured as immunoglobulins that inhibit thyrotropin binding and immunoglobulins that inhibit thyrotropin bioactivity).
RESULTS: Thyrotropin-blocking antibodies were detected in 9 percent of the patients with goitrous autoimmune thyroiditis and in 25 percent of those with atrophic autoimmune thyroiditis. Among the 21 patients studied serially while receiving levothyroxine, thyrotropin-blocking antibodies disappeared in 15 (group 1), 7 of whom had goiter initially, and persisted in 6 (group 2), none of whom had goiter initially. Levothyroxine therapy was subsequently discontinued in these 21 patients. Six of those in group 1 (four with goiter) remained euthyroid (mean follow-up after discontinuation of therapy, 2.1 years), and nine became hypothyroid again within 3 months. All six patients in group 2 remained hypothyroid.
CONCLUSIONS: Hypothyroidism in some patients with autoimmune thyroiditis may be due to thyrotropin-blocking antibodies. The production of thyrotropin-blocking antibodies may subside, producing remissions of hypothyroidism. Chronic autoimmune thyroiditis may therefore cause transient as well as permanent hypothyroidism.
The New England Journal of Medicine8326513DOI: 10.1056/NEJM199202203260803https://www.nejm.org/doi/full/10.1056/NEJM19920220326080320 years later, Takasu published the other study on long-term flip-flops between hypo, hyper and euthyroidism. Here, the group is ascertaining how the blocking and stimulating antibodies predict the progression of the disease, causing remissions
Atrophic Thyroiditisdiagnosis, etiology, genes, TRAb, blocking, stimulating, Hashimoto's Graves', fibrosis, hypothyroidism, echogenicity, therapy, TSH1Jara, Luis J.; Vera-Lastra, Olga; Medina, Gabriela2008Atrophic Thyroiditis
Atrophic thyroiditis is an organ-specific autoimmune disease characterized by thyroid autoantibodies, functional hypothyroidism, and absence of goiter. Atrophic thyroiditis is a rare entity, which occurs between the ages of 40–60 years especially in elderly women.
Immunogenetical analysis suggests that atrophic thyroiditis may be a distinct entity from Hashimoto’s disease. Genetic and environmental factors appear to interact leading to appearance of autoantigens with autoantibody formation. The frequency of HLA-DR8 and HLA-DQB1∗0302 is significantly increased in AT patients positive for TSH-binding inhibitor immunoglobulin compare with controls and goitrous autoimmune thyroiditis. Atrophic thyroiditis is a Th2 disease with blocking anti-TSH receptor antibodies. It has been suggested that Hashimoto's thyroiditis, primary myxedema or AT, and Graves’ disease are different expressions of a basically similar autoimmune process, and that the clinical appearance reflects the spectrum of the immune response in the particular patient. This response may include cytotoxic antibodies, stimulatory antibodies, blocking antibodies, or cell-mediated immunity.
The clinical presentation varies from asymptomatic AT, overt hypothyroidism, and myxedema. The pathological features are atrophic thyroid gland with lymphocytic infiltration and fibrous tissue replacing normal thyroid parenchyma.
There are no current diagnostic criteria for AT. We propose the following bases for AT diagnosis: clinic or subclinic hypothyroidism, positive thyroid stimulation blocking antibodies and thyroid ultrasound with diffuse low thyroid echogenicity associated with a reduced thyroid volume. In asymptomatic AT, preventive thyroid replacement therapy is indicated in patients with elevated basal TSH levels. Overt hypothyroidism always requires hormonal substitution.
Diagnostic Criteria in Autoimmune Diseases221-225https://link-springer-com.ezproxy.lib.ucalgary.ca/chapter/10.1007/978-1-60327-285-8_42Excellent overview of the genetic difference between AT and Hashimoto's. Says that AT also associates with "myxedema pericarditis, cardiac tamponade, dissecting aneurysm of the aorta, neuropsychological deficits, multiple sclerosis, and myocardial infarction"
Thyroid volumeAutoimmunity, statistics1Carlé, Allan; Pedersen, Inge Bülow; Knudsen, Nils; Perrild, Hans; Ovesen, Lars; Jørgensen, Torben; Laurberg, Peter2009Thyroid Volume in Hypothyroidism due to Autoimmune Disease Follows a Unimodal Distribution: Evidence against Primary Thyroid Atrophy and Autoimmune Thyroiditis Being Distinct Diseases
Context: Primary overt autoimmune hypothyroidism is often divided into primary idiopathic hypothyroidism with thyroid atrophy (Ord’s disease) and hypothyroidism with goitre (Hashimoto’s disease).
Objective: The aim of the present study was to characterize the two subtypes of disease.
Design and Setting: This was a population-based study identifying patients newly diagnosed with overt autoimmune hypothyroidism. Patients: We prospectively identified all patients with incident overt autoimmune hypothyroidism in a Danish population cohort, and 247 patients were invited to join a comprehensive program including thyroid ultrasonography and measurements of thyroid autoantibodies. Of the 144 patients investigated (58% of all invited), 139 were compared with 556 sex-, age-, and region-matched controls from the cohort.
Results: Patients had lower median (11.6 ml vs. 13.5 ml, P = 0.001) and a more dispersed distribution of thyroid volumes compared with controls (P < 0.001). Log thyroid volume showed a Gaussian distribution in both males and females with no bimodal pattern. Nearly all patients had measurable thyroid autoantibodies, but with increasing thyroid volume (quartile I, II, III, and IV), levels of circulating antibodies were higher (median thyroid peroxidase autoantibody 1540, 3122, 4686, and 7058 kU/liter; median thyroglobulin autoantibody 72, 143, 119, and 1195 kU/liter), and thyroid volume correlated negatively with echogenicity (r = −0.21, P = 0.011). Patients with the smallest volumes were biochemically more hypothyroid at diagnosis (median serum T4 21.0, 45.5, 45.0, and 36.7 nmol/liter; median serum TSH 81.0, 40.9, 45.4, and 55.6 mU/liter). No difference between groups was observed in prevalence of TSH receptor autoantibody (14.7, 5.6, 14.7, and 8.3%) or duration of symptoms before hypothyroidism was diagnosed.
Conclusions: In primary autoimmune hypothyroidism, thyroid volume follows a normal distribution. Cases with thyroid atrophy and goiter are only extremes within this distribution and do not represent separate disorders. However, patients with low vs. high thyroid volume differ with respects to several characteristics.
The Journal of Clinical Endocrinology & Metabolism394833-83910.1210/jc.2008-1370http://press.endocrine.org.ezproxy.lib.ucalgary.ca/doi/abs/10.1210/jc.2008-1370"Moreover, Ord’s disease has been suggested to be the end stage of Hashimoto’s disease, but repetitive biopsies of thyroid glands have not supported this idea (18, 19), and no difference has been recorded in age at presentation of the two disorders (7).
Hyper-HypoTSAb, TBAb, 10 years, Japan, hypothyroidism, Graves' disease, euthyroidism, antibody disappearance, Thyroid volume1Takasu, Nobuyuki; Matsushita, Mina2012Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism and in 98 TSAb-Positive Graves' Patients with Hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients
TWO TRABS: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves' hyperthyroidism.
TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb.
We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs.
TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years.
All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism.
Journal of Thyroid Research201218217610.1155/2012/182176Important study of flip-flops between hypo, hyper and euthyroidism over 10 years. Antibodies can disappear. Once the gland is atrophied, a person stays hypo.
Hyper-HypoTSAb, TBAb, T4 therapy, Graves' diasease, pregnancy, humans, mice,1McLachlan, Sandra M.; Rapoport, Basil2013Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa
Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.”
Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction.
Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo.
Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves' disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition.
The occurrence of “switching” emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare “switch” patients and appropriate Graves' and Hashimoto's controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity.
Thyroid12314-2410.1089/thy.2012.0374http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539254/Examines the triggers of switching from hypo to hyper, or vice versa. LT4 therapy can cause stimulating antibodies to resurge; Anti-thyroid therapy can cause blocking antibodies to dominate.
AntibodiesStats, stimulating, TBII, controls, Hashimoto's, Graves, euthyroid, hypothyroid1Diana, T.; Krause, J.; Olivo, P. D.; König, J.; Kanitz, M.; Decallonne, B.; Kahaly, G. J.2017Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease
The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII).
A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb.
In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively.
Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three.
TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = –0·86, P < 0·05).
The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with > 70% inhibition, 87% were TBII-positive.
Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.
Clinical & Experimental Immunology3189304-30910.1111/cei.12980http://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1111/cei.12980/abstractImportant frequency data in 1,079 AITD patients using both the TBAb assay and the TBII assay. 82 patients had blocking antibodies, and 48% of those were hypothyroid.
Atrophic ThyroiditisTSH, hypothyroidism, euthyroidism2Bonnyns, M.; Bastenie, P. A.1966Thyroid-stimulating hormone in the serum of patients with clinical hypothyroidism or asymptomatic atrophic thyroiditis
Several workers have demonstrated high serum-levels of thyroid-stimulating hormone (TSH) in cases of untreated primary hypothyroidism. Morphological and serological observations support the concept that primary hypothyroidism is the end-result of a process of atrophic lymphatic autoimmune thyroiditis. The not infrequent finding of antithyroid autoantibodies in the serum of patients with neither goitre nor signs of thyroid disease can be related in most cases to latent "atrophic lymphocytic thyroiditis." Furthermore, these patients, when compared with controld, have a lowered mean serum-protein-bound iodine, increased serum-cholesterol, and abnormalities in iodine metabolism.
The Lancet7438287638-63910.1016/S0140-6736(66)90830-0http://www.sciencedirect.com/science/article/pii/S0140673666908300
Atrophic Thyroiditiseuthyroid, symptoms, antibodies, sex, age, diabetes, obesity2Bastenie, P. A.; Bonnyns, M.; Neve, P.; Vanhaelst, L.; Chailly, M.1967Clinical and pathological significance of asymptomatic atrophic thyroiditis: A condition of latent hypothyroidism
By the Boyden tanned-red-cell test, thyroglobulin antibodies (T.G.A.) have been detected in a large percentage of over 2000 patients admitted to hospital for various diseases. Post-mortem controls in nearly 250 cases with and without circulating T.G.A. have indicated a very high correspondence of these antibodies with the presence of a process of atrophic asymptomatic thyroiditis. This condition, which is to be distinguished from Hashimoto's thyroiditis, is prevalent in women and its incidence increases with age. Its development is associated with other autoimmune diseases, with diabetes, and with obesity. Although clinical signs of hypothyroidism are absent, biological signs are indicative of latent thyroid failure.
The Lancet7496289915–91910.1016/S0140-6736(67)91486-9
Atrophic Thyroiditiseuthyroid, symptoms, gland size, gland fibrosis, atherosclerosis, Hashimoto's, treatment2Bastenie, P. A.; Bonnyns, M.; Ermans, A. M.; Nève, P.; Vanhaelst, L.; Herlant, M.; Pasteels, J. L.1972CHAPTER 10 - Asymptomatic Atrophic Thyroiditis
This chapter discusses the clinical features, pathology, immunology, diagnosis, and treatment of asymptomatic atrophic thyroiditis. The term asymptomatic atrophic thyroiditis is used to designate lymphocytic thyroiditis developing without clinical signs in a gland of normal size or at least apparently normal on clinical examination. Although by definition asymptomatic, latent lymphocytic thyroiditis offers considerable clinical interest because of the complications it may carry, namely, definite hypothyroidism or atherosclerosis particularly in the coronary arteries. The frequency of asymptomatic lymphocytic thyroiditis varies a little. Whereas Hashimoto's thyroiditis is characterized by visible enlargement of the thyroid gland, most cases of atrophic thyroiditis show no macroscopic changes. Half the glands maintain a normal weight and quite a number decrease in weight and size. Microscopical lesions consist of tissue alterations with oncocytic metaplasia, lymphoid infiltrations, and varying degrees of fibrosis. The latter phenomenon is absent if the lesions are small and focal. Parenchymatous lesions, although sometimes discrete, are observed regularly in serial sections. In the affected parts, the thyroid follicles are reduced in size and contain little colloid, while the areas unaffected by thyroiditis show a normal structure. At first sight, it may seem surprising to want to treat an asymptomatic condition. However, this particular condition is liable to progress imperceptibly into definite hypothyroidism. Furthermore, it is attended by a serious risk of atherosclerosis, especially coronary atherosclerosis. Treatment with small doses of thyroid hormones, therefore, seems justified, particularly as this is an inoffensive, relatively cheap, and easily supervised form of treatment. In any case, it is an effective way of bringing down the excessive levels of serum cholesterol usually present in a patient affected with asymptomatic thyroiditis.
Thyroiditis and Thyroid Function229-260http://www.sciencedirect.com/science/article/pii/B9780080166285500158
Hyper-HypoGraves' disease, T3-toxicosis, 6 years, hypothyoroidism,2Kohut, W. Dennis; Anderson, Milton W.; Gharib, Hossein1982Triiodothyronine thyrotoxicosis complicating primary hypothyroidism in a patient with autoimmune thyroiditis
The progression of spontaneous primary hypothyroidism to a hyperthyroid state is a rare occurrence [l-8]. So far, thyrotoxicosis has been reported only after the initiation of thyroid hormone replacement therapy for hypothyroidism. No adequate explanation has been provided for this phenomenon. Recently, we saw a patient in whom thyrotoxicosis developed six years after the diagnosis of primary hypothyroidism. This case is unique for several reasons: First, the patient never received thyroid hormone replacement therapy. Second, his hyperthyroidism was caused by an excessive level of triiodothyronine (T3) rather than thyroxine (T4). Finally, the presence of autoimmune thyroiditis was substantiated by unequivocal serologic and cytologic evidence. Herein, we include the sequence of hypothyroidism complicated by hyperthyroidism in the expanding range of autoimmune thyroiditis and Graves’ disease.
The American Journal of Medicine572843-846
AntibodiesCase, stats, TBAb, cAMP, Graves', TSAb, Hashimoto's, subacute thyroiditis2Karlsson, F. Anders; Dahlberg, Per Anders; Ritzén, E. Martin1984Thyroid Blocking Antibodies in Thyroiditis
Serum from a woman with a history of Hashimoto's thyroiditis, who had given birth to two children with congenital hypothyroidism, contained potent TSH blocking activity. Immunoglobulin preparation from this serum abolished completely TSH‐stimulated cAMP production in human thyroid membranes. The blocking activity was associated with the IgG fraction absorbed to and eluted from a Protein A column. The stimulation of adenylate cyclase by a preparation of thyroid‐stimulating antibodies from a patient with Graves' disease was also inhibited by the antibodies. In contrast, no effect was observed upon fluoride‐stimulated cAMP production. The data indicate that the antibody activity was directed against the TSH receptor. Immunoglobulin preparations from 22 other patients with Hashimoto's thyroiditis and 16 patients with subacute thyroiditis were examined for the existence of TSH receptor blocking antibodies. A blocking activity was found in two of the 22 Hashimoto patients. No such activity was found in the patients with subacute thyroiditis. It appears that thyroid blocking antibodies sometimes contribute to hypothyroidism associated with Hashimoto's thyroiditis.
Acta Medica Scandinavica5215461–46610.1111/j.0954-6820.1984.tb17679.x
Atrophic ThyroiditisEtiology, prognosis2Bastenie, Paul A.; Bonnyns, Marc; Vanhaelst, Luc1985Natural history of primary myxedema
It is generally admitted that primary myxedema in adults is the outcome of autoimmune atrophic thyroiditis. The present review traces the natural history of this process from its incipient biologic and genetic anomalies up to its protracted asymptomatic course, clinical development, and eventual lethal complications. The apprehension of preclinical hypothyroidism may change a clinician's outlook on early diagnosis and therapy.
The American Journal of Medicine17991-10010.1016/0002-9343(85)90551-0http://www.sciencedirect.com/science/article/pii/0002934385905510
Atrophic ThyroiditisIgG, hypothyroidism, TBBb, blocking stimulating, thyroid uptake,2Konishi, J.; Iida, Y.; Kasagi, K.; Misaki, T.; Nakashima, T.; Endo, K.; Mori, T.; Shinpo, S.; Nohara, Y.; Matsuura, N.1985Primary myxedema with thyrotrophin-binding inhibitor immunoglobulins. Clinical and laboratory findings in 15 patients
In a screening of 43 patients with primary myxedema, 9 patients were found to have IgG that inhibits the binding of 125I-thyrotrophin to its receptor (thyrotrophin-binding inhibitor immunoglobulins). Preparations of IgG from these patients did not stimulate thyroidal cyclic adenosine monophosphate generation and blocked thyroid stimulation by thyrotrophin in vitro. Clinical and laboratory features of 15 patients with this inhibitor, including 6 who were previously known, were compared with those of patients without the inhibitor. The patients with inhibitor, 2 men and 13 women, had onset of their hypothyroidism from age 2 to 49 years, and thyroid uptake in these patients was significantly lower than that in patients without inhibitor. Transient hypothyroidism was seen in all 5 infants born to 4 mothers having potent inhibitor immunoglobulins. These clinical findings indicate that thyrotrophin-receptor-blocking antibodies play a pathogenic role in a group of patients with primary myxedema.
Annals of Internal Medicine110326-31
AntibodiesHashimoto's, Atrophic thyroiditis, TBII, cAMP, TSII, TGII, goitere size,2Takasu, N., Yamada, T., Katakura, M., Yamauchi, K., Shimizu, Y., & Ishizuki, Y.1987Evidence for thyrotropin (TSH)-blocking activity in goitrous Hashimoto’s thyroiditis with assays measuring inhibition of TSH receptor binding and TSH-stimulated thyroid adenosine 3’,5’-monophosphate responses/cell growth by immunoglobulins.
There are two forms of autoimmune thyroiditis that may cause hypothyroidism: autoimmune atrophic thyroiditis (primary idiopathic hypothyroidism or primary myxedema) and autoimmune goitrous thyroiditis (Hashimoto's disease). Patients with the former have impalpable thyroid glands, and those with the latter have goiters.
We studied TSH binding inhibitory immunoglobulins (TBII), TSH-stimulated cAMP response inhibitory immunoglobulins (TSII), and TSH-stimulated cell growth inhibitory immunoglobulins (TGII) in 42 patients with the former (group 1) and 115 patients with the latter (group 2). Porcine thyroid cells in primary culture and rat thyroid cells in continuous culture (FRTL-5 cells) were used to study TSII and TGII activities, respectively; TSII was expressed as percent inhibition of 0.1 mU/ml TSH-stimulated cAMP response by the patient's immunoglobulin (IgG; 1 mg/ml) during 2-h incubation, and TGII was expressed as percent inhibition of 10 mU/ml TSH-stimulated [14C]thymidine incorporation by the patient's IgG (1 mg/ml) during 24-h incubation.
The new findings in this report are: some patients in both groups had TBII, TSII, and/or TGII; the frequency of the presence of TBII, TSII, and TGII in the patients with autoimmune atrophic thyroiditis was higher than that in the patients with autoimmune goitrous thyroiditis, and TSII and TGII were significantly associated with autoimmune atrophic thyroiditis; no correlation was found between goiter size and TBII, TSII, or TGII activity; and there were good correlations between TBII, TSII, and TGII activities. We also found that TSH-stimulated thymidine incorporation was through cAMP production and that the inhibitory IgGs inhibited TSH-stimulated thymidine incorporation by decreasing cAMP production in FRTL-5 cells, but not in porcine or human thyroid cells.
The Journal of Clinical Endocrinology and Metabolism264239-245.https://doi.org/10.1210/jcem-64-2-239https://www.ncbi.nlm.nih.gov/pubmed/2878935An early study that acknowledged atrophic vs. goitrous forms of autoimmune hypothyroidism. Examines TBII and two other tests.
AntibodiesTSAb, TBAb, hypothyroidism, Graves, TBII, Hyper-hypo2Kasagi, K.; Takeda, K.; Goshi, K.; Takamatsu, J.; Hidaka, A.; Hatabu, H.; Misaki, T.; Iida, Y.; Kuma, K.; Konishi, J.1990Presence of Both Stimulating and Blocking Types of Tsh-Receptor Antibodies in Sera from Three Patients with Primary Hypothyroidism
A case report of three patients with primary hypothyroidism who had potent TSH-binding inhibitor immunoglobulins (TBII) and both thyroid stimulating (TSAb) and thyroid stimulation-blocking antibodies (TSBAb) has been described.
Two patients displayed symptoms and signs indistinguishable from those in primary myxoedema (cases 1 and 2), and another patient had a history of Graves'disease (case 3). TBII, TSAb and TSBAb activities were 90.0, 1084.2 and 94.5% in case 1, 91.5, 826.6 and 95.8% in case 2, 76.0, 230.0 and 95.0% in case 3, respectively (normal range, < 11.0%, < 145.0 and < 22.0%, respectively.
The results indicate that both stimulating and blocking types of TSH-receptor antibodies exist in these patients. The possible mechanism whereby hypothyroidism developed has been discussed.
Clinical Endocrinology232253-26010.1111/j.1365-2265.1990.tb00861.xhttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1111/j.1365-2265.1990.tb00861.x/abstractBoth antibodies can coexist in the same patient, as shown in three cases.
Hyper-HypoTBAb, TSAb, 3 years, case, cAMP, TSH2Kralem, Z.; Baron, E.; Kahana, L.; Sadeh, O.; Shelnfeld, M.1992Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper-thyroidism and back to hypothyroidism
We report a patient who underwent, over a mere 3-year period, three successive cycles of oscillation from hypo to hyper-thyroidism and back to hypothyroidism. This unusual sequence of events originated in a rare passage of primary hypothyroidism to hyper-thyroidism. The hyperthyroldlsm seemed typical of the autoimmune subgroup of toxic multlnodular goitre.
Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper-thyroidism.
Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody In several serum samples from the patient. Throughout the whole course of alterations In thyroid function, thyroid stimulating antibodies were present.
This was not the case with thyrotrophln receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism
Clinical Endocrinology236211-21410.1111/j.1365-2265.1992.tb00960.xhttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1111/j.1365-2265.1992.tb00960.x/abstractCase study over 3 years, 3 cycles of hyper-hypo in 1 patient. While the TSAb seemed to be constant in this patient, the TBAb disappeared and resurfaced. The reemergence of TBAb caused a hypothyroid episode.
AntibodiesAtrophic thyroiditis, Hashimoto's, Graves' disease, polyglandular autoimmune syndrome, genets, TRAb, assays, sex, age, cholesterol, goiter2Eber, O., & Langsteger, W.1994[Clinical aspects of autoimmune thyroid diseases]. [article in German]
AITD (autoimmune thyroid disease) comprise atrophic thyroiditis (AT), hypertrophic Hashimoto's thyroiditis (HT), and immunogenic hyperthyroidism (Graves' disease, GD). Combinations with other types of autoimmune disorders frequently occur and are called polyglandular autoimmune syndrome. Familial disposition may be documented by genetic markers: GD and AT are associated with HLA-B8 and DR3 respectively, while HT associates with DR5.
Pathogenesis of the fore-mentioned 3 AITD may be explained on the one hand by an immunological balance and on the other hand by a predominance of either stimulating or destructive/blocking immune processes. In diagnosing AITD the determination of antibodies against thyroglobulin or thyroidal peroxidase have been in use for quite some times.
Antibodies directed against TSH receptors (TRAb) are determined by means of a radioligand assay which will not distinguish between stimulating or blocking antibodies, so that clinical symptoms and thyroid function parameters are essential in evaluating hyper- oder hypothyroid function. TRAb are transferred via the placenta and should therefore be determined in patients with AITD within the 3rd trimester of pregnancy. The prevalence of AITD is far higher in iodine rich countries and is 4 times more frequent in women, with a general age peak between the 5th and 6th decade.
The rare AT mostly presents as primary myxoedema and is discovered less frequently during the exploration of an unclear hypercholesterolemia. In HT we differentiate between the chronic fibrous and the juvenile oxiphilic variant. In the former fibrosis is predominant with plasmacellular infiltration producing extremely high titers of antibodies enabling diagnosis without fine needle biopsy (FNB). In the latter, the oxiphilic variant, titers of antibodies are mostly low or even missing so that a reliable diagnosis will require a FNB. However, two thirds of adolescent goitres are caused by HT.
Acta Medica Austriaca1211-7.https://www.ncbi.nlm.nih.gov/pubmed/8017160
Atrophic ThyroiditisUltrasound, echogenicity, thyroid volume, scintigraphy, RAIU, TPOAb2Vitti, P., Lampis, M., Piga, M., Loviselli, A., Brogioni, S., Rago, T., … Martino, E.1994Diagnostic usefulness of thyroid ultrasonography in atrophic thyroiditis.
An abnormal thyroid echographic pattern, characterized by a diffuse low thyroid echogenicity associated with a reduced thyroid volume, was found in 53 of 55 (96%) patients with atrophic thyroiditis.
In 10 of these patients, the ultrasound examination was diagnostic for thyroid atrophy, whereas the scintiscan had no abnormality. In only two cases was the reverse observed, ie, absent thyroid radioiodine uptake and no evidence of abnormality in the ultrasound examination.
Six out of 24 (25%) patients with thyroperoxidase antibody titers < or = 1:1600 and 4 of 31 (13%) patients with titers > or = 1:6400 had a normal thyroid scintiscan in the presence of an abnormal thyroid echographic pattern.
Thus, thyroid echography can be considered the first morphological procedure in patients with hypothyroidism due to atrophic thyroiditis, and thyroid scintiscan can be used to confirm the diagnosis when other results are not definitive.
Journal of Clinical Ultrasound622375–379.
Atrophic ThyroiditisTBII, follicular atrophy, epithelial flattening, thyroglobulin, epithelial destruction1Sugenoya, A., Itoh, N., Kasuga, Y., Kobayashi, S., Ohhashi, T., Nagai, N., & Iida, F.1995Histopathological features of atrophic thyroiditis with blocking type-TSH binding inhibitor immunoglobulins.
To investigate the histopathological features of atrophic thyroiditis (AT) with blocking type-TSH binding inhibitor immunoglobulins (TBII), the present morphological observations were carried out employing additional immunohistochemical procedures. Moreover, these were compared with examples of goitrous Hashimoto's thyroiditis showing negative TBII (HT).
There exist apparent differences between AT and HT. In particular, significant follicular atrophy with epithelial flattening including decreased positive staining of the follicular epithelial cells for thyroglobulin in AT was characteristically observed.
These results suggest that the mechanism for the development of hypothyroidism in AT with blocking type-TBII might be due to suppression of thyroid cell function through the inhibition of endogenous TSH stimulation by the blocking antibody with subsequent epithelial degenerative destruction.
Endocrine Journal242277–281.https://www.ncbi.nlm.nih.gov/pubmed/7627273Confirms that thyroid atrophy is caused by TSH blocking antibodies measured on a TBII test, and that Atrophic Thyroiditis is different from Hashimoto's in its antibody profile
AntibodiesTSAb, TBAb, TBII, Hashimoto's, atrophic thyroiditis, Hyper-hypo, euthyroid,2Orgiazzi, J., Madec, A.-M., & Ducottet, X.2003The role of stimulating, function-blocking and growth-blocking anti-TSH receptor antibodies (TRAbs) in GD, Hashimoto’s disease and in atrophic thyroiditis.
The prevalence of TBII ranges from 0 to 44% in goitrous thyroiditis (mean: 9%) and from 0 to 54% (mean: 21%) in atrophic thyroiditis (primay myxedema). For TSBAb, the corresponding figures are 0-44% (mean: 12%) and 0-62% (mean: 33%), respectively [5]. In the report of Cho et al, the prevalence of TBII is 6.3 and 48.0%, and that of TSBAb 10.5 and 59% for goitrous and atrophic thyroiditis, respectively [2].
Clearly, the prevalence of TSBAb is higher in non goitrous than goitrous autoimmune thyroiditis as well as in overt than in subclinical hypothyroidism or euthyroid thyroiditis [1]. In the few series reported, reversibility of autoimmune hypothyroidism may be observed in 0 to 24% of the patients. Is this condition predictable? Takasu et al. found TSBAb in 10% of patients with goitrous autoimmune thyroiditis and 25% of those with the atrophic form [23]. During a maximum follow up period of 11 years, of the 21 patients with blocking antibodies, 15 became negative. Among them, 6 remained euthyroid after thyroxine treatment withdrawal. In contrast, in the 6 TSBAb-positive patients with atrophic thyroiditis, blocking antibodies and hypothyroidism persisted for the whole follow up [23].
On the whole, measurement of TSBAb is not a specific marker of spontaneous recovery from hypothyroidism because disappearance of the antibody is not necessarily parallel to that of hypothyroidism. Spontaneous evolution of hyperthyroid GD to hypothyroidism has been characterized and, in many cohorts with long term follow up of 10-15 years, occurs in 2,1-2,8% of the patients treated with ATD [9]. Different mechanisms may be involved. While development of destructive autoimmune thyroiditis has been observed, presence of TSBAb is demonstrated in 20-40% of the cases [24].
TSBAb may apparently result from a conversion of the bioactivity of TSAb or coexist with TSAb at the time of hypothyroidism. TBII is usually detectable. In most cases, hypothyroidism is definitive so that the presence of TBII is not, in itself, an indicator of subsequent normalization.
More than 60 cases of fluctuating thyroid function have been reported, most of them with the spontaneous evolution of hypo to hyperthyroidism [5]. In a few cases, cycles of transition from hypo to hyper to hypothyroidism or the converse have been observed [10], [12]. Determination of the TRAb, TBII and stimulating/blocking antibodies, is useful to try and characterize these unusual anecdotal cases although there is not always a concordance between thyroid status and the net bioactivity of TSHR-Ab.
Annales D’endocrinologie16431–36.http://www.em-consulte.com/en/article/75826Discusses the use of TBII and TBAb tests and says that they are not useful for predicting future changes in thyroid status (hypo / hyper flips). Obviously the antibody titre is not reflective of the degree of hypothyroidism, since antibodies can disappear after the gland is permanently atrophied
AntibodiesTSH, Graves' disease2Brokken, J. S.; Wiersinga, M.; Prummel, F.2003Thyrotropin Receptor Autoantibodies Are Associated with Continued Thyrotropin Suppression in Treated Euthyroid Graves’ Disease Patients
Antithyroid treatment effectively restores euthyroidism in patients with Graves’ hyperthyroidism. After a few months of treatment, patients are clinically euthyroid with normal levels of thyroid hormones, but in many patients TSH levels remain suppressed.
We postulated that TSH receptor autoantibodies could directly suppress TSH secretion, independently from thyroid hormone levels, via binding to the pituitary TSH receptor.
To test this hypothesis, we prospectively followed 45 patients with Graves’ hyperthyroidism who were treated with antithyroid drugs. Three months after reaching euthyroidism, blood was drawn for the analysis of thyroid hormones, TSH, and TSH binding inhibitory Ig (TBII) levels.
After 6.7 ± 1.5 months since start of antithyroid treatment, 20 patients still had detectable TBII levels, and 25 had become TBII negative. The two groups had similar levels of free T4 and T3, but TBII-positive patients had lower TSH values than TBII-negative patients: median 0.09 (range < 0.01-4.30) mU/liter vs. 0.84 (0.01-4.20; P = 0.015). In addition, TSH levels correlated only with TBII titers (r = −0.424; P = 0.004), and not with free T4 or T3 values.
Our findings suggest that TBII suppress TSH secretion independently of thyroid hormone levels, most likely by binding to the pituitary TSH receptor.
The Journal of Clinical Endocrinology & Metabolism9884135–413810.1210/jc.2003-030430Theorizes that the TSAb activity on the TSH receptors on the pituitary gland itself are responsible for continued TSH suppression after treatment for hypERthyroidism. I believe the same feedback loop may cause excess TSH in TBAb patients.
AntibodiesTSAb, TBAb, Graves', Hypothyroidism, TBII,2Morgenthaler, Nils G.; Ho, Su Chin; Minich, Waldemar B.2007Stimulating and Blocking Thyroid-Stimulating Hormone (TSH) Receptor Autoantibodies from Patients with Graves’ Disease and Autoimmune Hypothyroidism Have Very Similar Concentration, TSH Receptor Affinity, and Binding Sites
Objective: The distinct biological properties of TSH receptor (TSH-R) autoantibodies (TRAbs) from patients with Graves’ disease (GD) are yet unexplained on the molecular level. Here we compare serum concentration, affinity to the TSH-R, and binding sites on the TSH-R of stimulating (TSAb) and blocking (TBAb) TRAbs.
Methods and Patients: Four-step affinity purification using human recombinant TSH-R was performed with 22 TRAb-positive sera from GD patients (11 with only TSAb and 11 with only TBAb) and five control sera. Antibody concentration, TSH binding inhibition (TBII), and TSAb/TBAb activity of the purified TRAb were assessed. Labeled purified TRAbs were used for displacement studies with TRAb and an additional 30 patients and 10 control sera.
Results: TRAbs could be purified to 80–93% purity with recovery of the TBII and TSAb and TBAb activity. No TRAbs could be purified from healthy individuals. The mean ± sd concentration of TRAb was 17.3 ± 5.4 μg/IU for the TSAb sera (range, 9.6–25.9) and 18.2 ± 8.5 μg/IU for the TBAb sera (range, 4.6–29.2), respectively (P = 0.79). Affinity was in the picomolar range for both TRAb subtypes with mean ± sd dissociation constant of 167 ± 109 pm (60–410 pm) for TSAb and 253 ± 132 pm (80–410 pm) for TBAb (P = 0.12). Purified and labeled TSAb and TBAb showed a very similar binding pattern to the TSH-R in displacement studies with unlabeled TSAb/TBAb or unpurified patients sera, indicating binding sites on the TSH-R in close proximity to each other.
Conclusion: TSAbs and TBAbs in the serum of patients with GD have similar characteristics. They are of low concentration with high affinity and have also similar binding epitopes on the TSH-R.
The Journal of Clinical Endocrinology & Metabolism3921058-106510.1210/jc.2006-2213https://academic-oup-com.ezproxy.lib.ucalgary.ca/jcem/article/92/3/1058/2597815Special tests describe the concentrations & behavior of TSHR antibodies and how they bind to the receptor.
Hyper-HypoGoiter, TGAb, TPOAb, hypothyroidism, Hashimoto's, Atrophic thyroiditis, TBAb, T4 therapy, recovery2Takasu, N., & Yoshimura Noh, J.2008Hashimoto’s thyroiditis: TGAb, TPOAb, TRAb and recovery from hypothyroidism.
Hashimoto described four patients with goiter. The histology of the goiter was characterized by diffuse lymphocytic infiltration, fibrosis and epithelial cell destruction. Thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) have been used to diagnose Hashimoto's thyroiditis. Patients with positive TGAb and/or TPOAb have been assumed to have Hashimoto's thyroiditis. Approximately 10% of those with positive TGAb and/or TPOAb have hypothyroidism. There are two types of autoimmune thyroiditis: goitrous Hashimoto's thyroiditis and atrophic thyroiditis. The latter patients have blocking antibody (thyroid-stimulating hormone [TSH]-stimulation blocking antibody [TSBAb]). TSBAb is a TSH-receptor antibody (TRAb). TSBAb causes thyroid atrophy and hypothyroidism. TGAb and/or TPOAb do not necessarily cause hypothyroidism. Hypothyroid patients with Hashimoto's thyroiditis usually receive life-long l-thyroxine therapy. However, spontaneous recovery from hypothyroidism has been reported. Patients who had Hashimoto's hypothyroidism and then Graves' hyperthyroidism (and vice versa), have also been reported. Hashimoto's hypothyroidism and Graves' hyperthyroidism could be the opposite spectrums of one disease.
Expert Review of Clinical Immunology24221–237https://doi.org/10.1586/1744666X.4.2.221https://www.ncbi.nlm.nih.gov/pubmed/20477052
AntibodiesTBAb, children, Hashimoto's, Thyroid volume, TSH, goiter, TBII, cAMP2Feingold, Shiri B.; Smith, Jessica; Houtz, Jeff; Popovsky, Erica; Brown, Rosalind S.2009Prevalence and Functional Significance of Thyrotropin Receptor Blocking Antibodies in Children and Adolescents with Chronic Lymphocytic Thyroiditis
Context: TSH receptor (TSHR) blocking antibodies (Abs) inhibit TSH-induced thyroid growth and function in some adults with chronic lymphocytic thyroiditis (CLT), but their role in the pediatric age range is unknown.
Objectives: Our objectives were: 1) to determine the prevalence of TSHR blocking Abs in children and adolescents with CLT and 2) assess their functional significance both in vivo and in vitro.
Design and Setting: This was a retrospective study in a referral outpatient setting.Patients: Sera from a total of 87 CLT patients and 33 controls were studied.
Main Outcome Measures: TSHR Abs were measured by both ELISA and bioassay.
Results: Eight of 87 children and adolescents with CLT (9.2%), including one as young as 4 yr of age, had TSHR Abs in serum as measured by ELISA. The prevalence was significantly higher in individuals whose serum TSH concentration was 20 mU/liter or greater within 3 months of study than in less hypothyroid patients (eight of 45 vs. none of 42, P &lt; 0.005). Conversely, TSHR Ab-positive patients were significantly more hypothyroid at diagnosis but only when the analysis was restricted to those with severe hypothyroidism was a decreased prevalence of goiter observed. IgG purified from TSHR Ab sera retained the TSH binding-inhibitory activity and TSHR Ab-positive sera inhibited TSH-induced stimulation of cAMP significantly more than normal.Conclusions:
TSHR-blocking Abs contribute significantly to the severity of the hypothyroidism in some children with CLT, but as compared with adults, they appear to play less of a role in determining the presence or absence of a goiter.
The Journal of Clinical Endocrinology & Metabolism12944742-474810.1210/jc.2009-1243https://academic-oup-com.ezproxy.lib.ucalgary.ca/jcem/article/94/12/4742/2596493Atrophic thyroiditis occurs at a similar rate in children, around 10% of hypothyroid cases, and it's associated with a TSH higher than 20 on diagnosis.
AntibodiesGraves' disease TSAb, Tbab, neutral,2Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.2009TSH receptor autoantibodies
Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves' disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs.
Autoimmunity Reviews29113-11610.1016/j.autrev.2009.03.012http://www.sciencedirect.com/science/article/pii/S1568997209000883
Atrophic ThyroiditisHashimoto's, TPOAb, TSAb, TBAb, Graves', eye disease,2Starrenburg-Razenberg, A. J.; Castro Cabezas, M.; Gan, I. M.; Njo, T. L.; Rietveld, A. P.; Elte, J. W. F.2010Four patients with hypothyroid Graves' disease
In autoimmune hypothyroidism (Hashimoto's disease), TPO (thyroid peroxidase) antibodies may be detected, while in autoimmune hyperthyroidism (Graves' disease) thyroid-stimulating hormone (TSH ) receptor antibodies (TSH -R-AB s) are frequently present. Less well known is the fact that autoimmune hypothyroidism can present with TSH-R-ABs and ophthalmic Graves' disease (OGD). This condition is also known as hypothyroid Graves' disease. In this report we describe four patients with this uncommon phenomenon. These four cases demonstrate that differences between Hashimoto and Graves' disease are less clear than expected. Hypothetically the thyroid cell might be 'attacked' by blocking and stimulating antibodies. Dependent on the relative concentrations, hypothyroidism or hyperthyroidism may occur. So the differences between Hashimoto's disease and Graves' disease, at least in these cases, may be gradual and small.
The Netherlands Journal of Medicine468178-180
AntibodiesTBABb, Graves, stimulating, blocking, Mabs, eye disease, hyperthyroidism, therapy2Furmaniak, Jadwiga; Sanders, Jane; Smith, Bernard Rees2013Blocking type TSH receptor antibodies
TSH receptor (TSHR) autoantibodies (TRAbs) play a key role in the pathogenesis of Graves’ disease. In the majority of patients, TRAbs stimulate thyroid hormone synthesis via activation of the TSHR (stimulating TRAbs, TSHR agonists).
In some patients, TRAbs bind to the receptor but do not cause activation (blocking TRAbs, TSHR antagonists). Isolation of human TSHR monoclonal antibodies (MAbs) with either stimulating (M22 and K1-18) or blocking activities (5C9 and K1-70) has been a major advance in studies on the TSHR.
The binding characteristics of the blocking MAbs, their interaction with the TSHR and their effect on TSHR constitutive activity are summarised in this review. In addition, the binding arrangement in the crystal structures of the TSHR in complex with the blocking MAb K1-70 and with the stimulating MAb M22 (2.55 Å and 1.9 Å resolution, respectively) are compared. The stimulating effect of M22 and the inhibiting effect of K1-70 on thyroid hormone secretion in vivo is discussed. Furthermore the ability of K1-70 to inhibit the thyroid stimulating activity of M22 in vivo is shown. Human MAbs which act as TSHR antagonists are potentially important new therapeutics. For example, in Graves’ disease, K1-70 may well be effective in controlling hyperthyroidism and the eye signs caused by stimulating TRAb. In addition, hyperthyroidism caused by autonomous TSH secretion should be treatable by K1-70, and 5C9 has the potential to control hyperthyroidism associated with TSHR activating mutations. Furthermore, K1-70 has potential applications in thyroid imaging as well as targeted drug delivery to TSHR expressing tissues.
Autoimmunity Highlights1426-Nov10.1007/s13317-012-0028-1https://link-springer-com.ezproxy.lib.ucalgary.ca/article/10.1007/s13317-012-0028-1Examines how the antibodies block TSH, and considers the development of therapies to help patients with stimulating antibodies.
Thyroid volumeStats, Turkey2Aydıner, Ömer; Karakoç Aydıner, Elif; Akpınar, İhsan; Turan, Serap; Bereket, Abdullah2015Normative Data of Thyroid Volume-Ultrasonographic Evaluation of 422 Subjects Aged 0-55 Years
Objective: To establish local normative data of thyroid volume assessed by ultrasonography in subjects aged 0-55 years living in İstanbul, Turkey. Methods: Subjects without any known history of thyroid disease, of major surgery and/or chronic disease were enrolled in the study and evaluated by physical examination and thyroid ultrasonography. Thyroid gland and isthmus at usual location, each lateral lobe volume with three dimensions, ectopic thyroid tissue and echogenicity of the gland were assessed. Results: Initially, 494 subjects were enrolled in the study. Subjects showing heterogeneous thyroid parenchyma (n=21) and/or nodule (n=51) in ultrasonography were excluded. Final analysis covered 422 subjects (216 males, 206 females). Thyroid volume was found to significantly correlate with height, weight, age and body surface area (r=0.661, r=0.712, r=0.772 and r=0.779, respectively; p<0.0001 for all). These correlations were even stronger in subjects younger than 18 years (r=0.758, r=0.800, r=0.815 and r=0.802, respectively; p<0.0001 for all). Conclusion: The study provides updated reference norms for thyroid volume in Turkish subjects which can be used in the diagnosis and follow-up of patients with thyroid diseases.
Journal of Clinical Research in Pediatric Endocrinology2798-10110.4274/jcrpe.1818https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563193/
AntibodiesTesting, blocking, stimulating, TBII, Graves, Hashimotos, Controls, stats2Diana, T.; Wüster, C.; Kanitz, M.; Kahaly, G. J.2016Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies
PurposeTSH-receptor (TSHR) antibodies (Ab) can be measured with binding or bio-assays. Sensitivity and specificity of five binding and two bio-assays were compared.MethodsTSHR-blocking (TBAb) and TSHR-stimulating (TSAb) Ab were measured with reporter bio-assays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bTSH alone. TSAb was reported as percentage of specimen-to-reference ratio (SRR%). TSHR-binding inhibitory immunoglobulins (TBII) were measured with Kronus, Dynex, Kryptor, Cobas, and Immulite.ResultsSixty patients with Graves’ disease (GD), 20 with Hashimoto’s thyroiditis (HT), and 20 healthy controls (C) were included. C tested negative in all assays (specificity 100 %) while all 60 hyperthyroid GD patients tested positive in the TSAb bio-assay (sensitivity 100 %). Among these 60 GD patients, 20 had low TSAb positivity (SRR% 140–279), but were TBII positive in only 20 (100 %), 7 (35 %), 9 (45 %), 11 (55 %), and 18 (90 %) using the Kronus, Dynex, Kryptor, Cobas, and Immulite, respectively. In 20 moderate TSAb-positive (SRR% 280–420) patients, TBII tested positive in 20 (100 %), 14 (70 %), 13 (65 %), 16 (80 %), and 19 (95 %), respectively. The high (SRR% > 420) TSAb-positive patients were all TBII positive. All 20 hypothyroid HT patients tested TBAb positive (sensitivity 100 %) in the bio-assay while they tested TBII positive in 20 (100 %), 18 (90 %), 20, 20, and 18, respectively. Results obtained with two luminometers correlated for TSAb positive (r = 0.99, p < 0.001), TBAb positive (r = 0.88, p < 0.001), and C (r = 0.86, p < 0.001). None of the binding assays differentiated between TSAb and TBAb.ConclusionsSensitivity is highly variable between binding and bio-assays for TSHR-Abs.
Journal of Endocrinological Investigation10391159-116510.1007/s40618-016-0478-9https://link-springer-com.ezproxy.lib.ucalgary.ca/article/10.1007/s40618-016-0478-9
Thyroid volumeHashimoto's, FT3, FT4, TSH, TGAb, T4 therapy, 2 years, hypothyroidism, euthyroid2Şahin, Serap Baydur2016Alterations of Thyroid Volume, Levels of Thyroid Hormone and Autoantibody in Women with Hashimotos Thyroiditis
Aim: Our aim was to investigate the changes in thyroid volume, thyroid hormone and autoantibody levels after 2 years in newly diagnosed euthyroid women with Hashimoto's thyroiditis (HT) and women with HT treated with levothyroxine (L-T4).
Material and Method: We enrolled 60 women with HT (mean age 39.6± 10.8 years) in this study. 27 patients were newly diagnosed and euthyroid (euthyroid group) and L-T4 group (n=33) consisted of women with HT treated with levothyroxine. Thyroid ultrasonography was performed and free T3 (fT3), free T4 (fT4), TSH, anti-thyroglobulin autoantibody (anti-TG) and anti-thyroid peroxidase autoantibody (anti-TPO) levels were measured. Thyroid volume was calculated with ellipsoid formula: (Volume (ml) = Length (cm) x Width(cm) x Thickness (cm) x 1/6 %u041B).
Results: Median thyroid volume increased in all subjects (8.6 (1.8-46) vs 10.8 (3.9-54.5) ml, p=0.008). While serum fT3 levels decreased (2.9± 0.5 vs 2.5± 0.3 pg/ml, p0.05). The change in thyroid volume was negatively associated with thyroid volume at basal (r= -0.290, p=0.027) and TSH (r=-0.271, p=0.039) and positively correlated with fT3 (r= 0.356, p= 0.006). While thyroid volume increased in euthyroid group (9.8 (6.6-35.1) vs 12.5 (6.9-54.5) ml, p=0.006), there was not a change in L-T4 group (7.5 vs 8.3 ml, p=0.428).
Discussion: Thyroid volume increased in euthyroid women with HT, however did not change in patients treated with levothyroxine in two years. While thyroid autoantibodies did not change in two groups, hypothyroidism developed in 7.4% of euthyroid subjects.
Journal of Clinical and Analytical Medicine3710.4328/JCAM.2691Hashimoto's does not involve gland atrophy, only gland enlargement or stasis, over two years.
AntibodiesStats, TPOAb, TSAb, TGAb, Graves, Cancer, Breast cancer, Hashimoto's2Fröhlich, Eleonore; Wahl, Richard2017Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases
Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases.
This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies.
In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis.
Frontiers in Immunology810.3389/fimmu.2017.00521https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422478/Prevalence of TG, TPO, and TSHR antibodies in autoimmune thyroid disease. Associations with cancers
Hyper-HypoSymptoms, autoimmunity2Brondfield, Sam; Feingold, Kenneth R.Symptomatic Graves’ Disease After Autoimmune Hypothyroidismsee full text of letter to editor in NotesThe American Journal of Medicine5129e19-e20http://www.amjmed.com/article/S0002-9343(15)30053-X/pdf
Hyper-HypoCase, Graves3Baldwin, W. W.1895Some cases of Graves' disease, succeeded by thyroid atrophy.The Lancet3725145145-14610.1016/S0140-6736(01)90908-0http://www.sciencedirect.com/science/article/pii/S0140673601909080
Atrophic Thyroiditis3Eve, F. C.1914Acute Atrophy Of The Thyroid Gland[Short article]The British Medical Journal28052583-583http://www.jstor.org/stable/25311327
Thyroid volumeCase3Allen, Arthur W.; Jones, Chester M.1949Case 35071 Atrophy of thyroid gland, with myxedema
Presentation of Case First admission. A forty-six-year-old carpenter was admitted to the hospital because of epigastric distress of eight years' duration. The pain usually developed in the midafternoon and was promptly relieved by food or soda. On one occasion he vomited large quantities of bright blood. Physical examination revealed a well developed man, with a blood pressure of 130 systolic, 80 diastolic. There was moderate exophthalmos and slight lid lag. The skin was slightly dry and cool. Examination of the chest and abdomen was negative. Urine, blood and stool examinations, including guaiac tests, were negative. Gastric analysis revealed 33 . . .
New England Journal of Medicine7240262-26710.1056/NEJM194902172400707http://dx.doi.org/10.1056/NEJM194902172400707
Atrophic ThyroiditisHeart disease3Bastenie, P. A.; Bonnyns, M.; Nève, P.; Vanhaelst, L.1972Asymptomatic atrophic thyroiditis in coronary heart-diseaseshort letter onlyThe Lancet77592991072–107210.1016/S0140-6736(72)91255-X
Atrophic ThyroiditisHypertension, heart disease, atherosclerosis, cholesterol, obesity3Bastenie, P. A.; Vanhaelst, L.; Nève, P.1972CHAPTER 12 - Atrophic Thyroiditis, Hypertension and Coronary Heart Disease
This chapter discusses the clinical features, pathology, immunology, diagnosis, and treatment of atrophic thyroiditis, hypertension and coronary heart disease (CHD). The idea that hypertension generally precedes rather than accompanies hypothyroidism is well demonstrated by the association of asymptomatic thyroiditis and hypertension. The results of a recent systematic investigation confirm this association. The mechanism by which asymptomatic thyroiditis favors the development of atherosclerosis is obscure. In studying the causes of atherosclerosis, one of the major difficulties lies in diagnosing vascular lesions in living subjects and in evaluating the intensity of the process. The chapter describes a study in which coronary atherosclerosis was taken as an indication of atherosclerosis, because it is in the coronary artery that the disease is the most marked and also the easiest to diagnose. Even if the diagnosis is made only by indirect means and CHD should be distinguished from coronary lesions of atherosclerosis, in the large majority of cases, the clinical and electrocardiographic signs of CHD are, in fact, due to lesions of coronary atherosclerosis. Several factors could play a pathogenic role in coronary atherosclerosis associated with asymptomatic thyroiditis: hypercholesterolemia; certain associated diseases such as obesity, hypertension, or diabetes; and some constitutional factor. If, indeed, asymptomatic thyroiditis constitutes a definite pathogenic factor in coronary atherosclerosis in women and a possible factor in men, the treatment of this condition would have the definite advantage of reducing an abnormality considered as a coronary risk factor.
Thyroiditis and Thyroid Function275-288http://www.sciencedirect.com/science/article/pii/B9780080166285500171
Atrophic Thyroiditisheart disease, case, T3 therapy, Cytomel3Thomas, J.; Mills, K. B.; Grisham, D. W.1978Primary myxedema heart disease
A case of primary myxedema heart disease in an 84-year-old man is presented. His history and physical examination were typical of myxedema. Electrocardiographic changes showing generalized low voltage, nonspecific S-T segment and T-wave changes, and nodal rhythm are characteristic of the disease. The patient showed remarkable improvement after oral liothyronine (Cytomel) therapy.
Journal of the National Medical Association1170833
AntibodiesThyroid volume, fibrosis, TGAb, hypothyroidism, T3, T4, TSH, Immunoglobulins, Graves, goiter3Drexhage, H. A.; Bottazzo, G. F.; Bitensky, L.; Chayen, J.1981Thyroid growth-blocking antibodies in primary myxoedema
Adult primary myxoedema is usually due to an autoimmune thryoiditis characterized by progressive shrinking of the thyroid gland, loss of epithelium, dense infiltration by sensitized lymphocytes and plasma cells with final replacement of the gland by a fibrous scar1. Antibodies directed against thyroglobulin (TgHA) and microsomal antibodies (McHA), detectable years before the onset of hormonal failure, and cell-mediated immune mechanisms contribute to the pathogenesis2. When 90% of the gland is destroyed, the secretion of thyroid hormones (T3/T4) falls below normal needs and pituitary thyrotrophs react by producing over 100 times the normal amount of thyroid-stimulating hormone (TSH)3 which should normally lead to regrowth of the gland as happens in goitrous Hashimoto thyroiditis4. The inability of the thyroid in primary myxoedema to respond to the trophic action of TSH suggested that blocking antibodies exist in this disease which compete with TSH for its receptors5,6. The trophic effect of TSH can be assayed in vitro by measuring DNA-synthesis by Feulgen cytophotometry7; elevated pentose-shunt oxidative activity correlates with DNA synthesis8. Here we report that immunoglobulins from patients with adult, primary myxoedema block the trophic effect of TSH, as assessed by this in vitro system. This is in marked contrast to the growth stimulation induced by immunoglobulins from patients with thyrotoxic Graves' disease with prominent goitres7.
Atrophic ThyroiditisSjögren syndrome, Hashimoto's, submaxillary glands,3Wemeau, J. L., Dessaint, J. P., Leonardelli, J., Rouget, J. P., Racadot, A., & Linquette, M.1983[Hypothyroidism and the Gougerot-Sjögren syndrome]. [article in French]
The signs of Sjögren's syndrome were systematically researched in 36 patients with hypothyroidism
(myxoedema with atrophic thyroiditis in 32 cases, Hashimoto's thyroiditis in 4).
In a quarter of these patients were noted separately submaxillary glands and/or parotids enlarged, buccal and/or lacrymal sicca syndromes, and antisalivary ducts antibodies. The histologic analysis of minor salivary glands revealed foci of lymphocytes and plasmocytes (grades 3 and 4 of Chisholm's classification) in 6 subjects. Similarities between the Sjögren's syndrome and the autoimmune thyroiditis were specified; their association in the same patients might be explained considering the genetic predisposition to these affections.
Annales De Medecine Interne4134288–292.
AntibodiesTBAb, hypothyroidism, lab study, 28 patients, bovine TSH, IgG3Steel, N R; Weightman, D R; Taylor, J J; Kendall-Taylor, P1984Blocking activity to action of thyroid stimulating hormone in serum from patients with primary hypothyroidism.
Spontaneous primary hypothyroidism in adults is usually associated with autoimmune thyroiditis. The hypothesis that hypothyroidism may result from the presence in serum of a factor that blocks stimulation of the thyroid by thyroid stimulating hormone was examined. Serum samples were collected from 28 patients with recently diagnosed primary hypothyroidism. After removal of endogenous thyroid stimulating hormone the effect of the serum on secretion of triiodothyronine induced by thyroid stimulating hormone or thyroid stimulating antibodies was examined in thyroid slices incubated in vitro. Serum samples from six of the patients demonstrated significant blocking of the stimulation by bovine thyroid stimulating hormone. Inhibition of the stimulatory action of thyroid stimulating antibodies was also exhibited by serum samples with blocking activity. It is concluded that in some patients with primary hypothyroidism a serum factor, which is probably an IgG, exists that can block the thyroid response to thyroid stimulating hormone and thyroid stimulating antibodies; it may represent an important mechanism in the pathogenesis of hypothyroidism.
British Medical Journal (Clinical research ed.)64302881559-1562https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1441235/
Atrophic ThyroiditisAtrophic thyroiditis, cAMP, TBAb, TSAb, hypothyroidism, euthyroid3Takasu, N., Naka, M., Mori, T., & Yamada, T.1984Two types of thyroid function-blocking antibodies in autoimmune atrophic thyroiditis and transient neonatal hypothyroidism due to maternal IgG.
We examined the effects of IgG from four patients with autoimmune atrophic thyroiditis on cAMP responses and iodine metabolism (post-receptor processes), using cultured thyroid cells. We found two types of thyroid function-blocking antibodies: (1) one blocks TSH binding to its receptors and inhibits TSH-stimulated cAMP responses but does not block cAMP-stimulated iodine uptake and organification; (2) the other blocks TSH binding to its receptors, inhibits TSH-stimulated cAMP responses and does block cAMP-stimulated iodine uptake and organification (post-receptor processes). Among the four patients with autoimmune atrophic thyroiditis, three had TSH binding blocking antibodies only and one had antibodies which block post-receptor processes. These antibodies might be responsible for thyroid dysfunction in autoimmune atrophic thyroiditis. The daughter of one of the women with autoimmune atrophic thyroiditis had transient neonatal hypothyroidism and recovered spontaneously from the hypothyroid state with the disappearance of the maternal blocking antibodies.
Clinical Endocrinology421345–355.
Hyper-HypoCase, TRAb, cAMP, TBII, biopsy, Hashimoto's3McDermott, Michael T.; Kidd, Gerald S.; Dodson, Leonard E.; Hofeldt, Fred D.1986Case Report: Hyperthyroidism Following Hypothyroidism
Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves’ disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.
The American Journal of the Medical Sciences3291194-19810.1097/00000441-198603000-00011http://www.sciencedirect.com/science/article/pii/S0002962915370105
AntibodiesBlocking, hypothyroidism, gland atrophy, Hashimoto's, TBII, transient neonatal hypo3Cho, Bo Youn; Shong, Young Kee; Lee, Hong Kyu; Koh, Chang Soon1989Role of Blocking TSH Receptor Antibodies on the Development of Hypothyroidism and Thyroid Atrophy in Primary Myxedema
We studied blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgG to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increases and 3H-thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin (TBII), thyroid stimulation blocking antibody (TSBAb) and thyroid growth blocking antibody (TGBAb) in patients with primary myxedema were 53.6%, 75% and 65.2%, respectively. However, in goitrous Hashimoto's thyroiditis, these were 14.3%, 0% and 17.7%, respectively. These antibodies inhibited the receptor binding of 125I-bTSH dose-dependently, and also inhibited dose-dependently not only TSH-stimulated but also Graves' IgG-stimulated cAMP increase and 3H-thymidine incorporation. TBII activities of patients with primary myxedema were significantly correlated with both their TSBAb (r = 0.665; p less than 0.01) and TGBAb (r = 0.618; p less than 0.01) activities. Thirteen patients whose TBII activities were more than 50% had both strong TSBAb (75.1-100%) and TGBAb (57.4-100%) activities. Transient neonatal hypothyroidism was found in an infant born to a mother having potent TBII activities. Serum of the baby also had potent TBII activities and the baby's IgG inhibited TSH-stimulated cAMP increase and 3H-thymidine incorporation. These data suggest that a significant proportion of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibition of TSH-stimulated cAMP generation.
The Korean Journal of Internal Medicine24108
Hyper-HypoTSAb, TBII, TBAb, goiter, hyperthyroidism, hypothyroidism, two cases, comparison3Shong, Young Kee; Cho, Bo Youn; Hong, Sung Kwan; Lee, Hong Kyu; Koh, Chang-Soon; Min, Hun Ki1989Pathogenetic Role of Thyrotropin Receptor Antibody in the Development of Hyperthyroidism Following Primary Hypothyroidism*
The authors measured thyrotropin binding inhibitory immunoglobulin (TBII), thyroid stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) sequentially in patients who developed hyperthyroidism following primary hypothyroidism, and compared changes in these various funcional parameters of thyrotropin receptor antibody (TRAb) with clinical manifestations, in order to investigate the role of TRAb in the development of hyperthyroidism following primary hypothyroidism., In a patient with goitrous chronic thyroiditis, TBII, TSAb and TSBAb were not detected at the initial hypothyroid phase. But with appearance of TBII and TSAb, the patient developed hyperthyroidism. In a patient with primary nongoitrous myxedema, initially high TBII and TSBAb were detected without TSAb activity. His TSBAb disappeared and TSAb appeared with development of goiter growth and hyperthyroidism., These two mechanisms, that is, appearance of previously absent TSAb and conversion of TSBAb to TSAb, might play a causative role in the development of hyperthyroidism following primary hypothyroidism. These phenomena might be evidence that Graves’ disease, chronic thyroiditis, and primary nongoitrous myxedema are on a continuing spectrum of a common syndrome sharing similar pathophysiology, at least with respect to TRAb.
The Korean Journal of Internal Medicine24118-12410.3904/kjim.1989.4.2.118https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534979/
AntibodiesGoitrous, Hashimoto's, Atrophic thyroiditis, TBII, hypothyroidism, disappearance, TSAb, TBAb,3Sato, K., Okamura, K., Yoshinari, M., Ikenoue, H., Kuroda, T., Torisu, M., & Fujishima, M.1990Goitrous hypothyroidism with blocking or stimulating thyrotropin binding inhibitor immunoglobulins.
The significance of thyrotropin-binding inhibitor immunoglobulin (TBII) was evaluated in goitrous hypothyroidism associated with chronic thyroiditis (serum TSH greater than 10 mU/L, n = 148). TBII was measured by a RRA, and thyroid-stimulating antibody (TSab) and thyroid-stimulation-blocking antibody (TSBab) were determined using porcine thyroid cells. The prevalence of patients having TBII was 11% or 7.4% of 148 patients, which was not significantly different from that of 5% or 9.6% of 52 patients with atrophic thyroiditis. Although TBII was shown to be TSBab in 6, TSab was found in the other 5 patients despite hypothyroidism. There was little correlation between severity of hypothyroidism and TBII or TSBab activity. One patient continued to be latently hypothyroid despite apparently positive TSBab. Five other patients with TSBab and 2 patients with TSab suffered from overt, irreversible hypothyroidism, and 2 of the patients with TSBab continued to be hypothyroid even after the disappearance of TSBab. Biopsy of the thyroid gland performed in 4 patients revealed severely damaged thyroid follicles with mononuclear cell infiltration with or without fibrosis. Three of the patients with TSab had been taking excess iodine, and recovery of thyroid function was observed after iodine restriction. A perchlorate discharge test performed in two of these patients was positive, suggesting an iodide organification defect. These results indicate that, although TBII is not infrequently found in goitrous hypothyroidism, cellular or chemical damage of the thyroid gland plays an important role in the pathogenesis of thyroid hypofunction and TSBab may only have a precipitating role.
The Journal of Clinical Endocrinology and Metabolism471855–860.https://doi.org/10.1210/jcem-71-4-855
AntibodiesIGG, hypothyroidism, TSH, blocking stymulating3Cho, B. Y.; Shong, M. H.; Chung, J. H.; Lee, H. K.; Koh, C. S.; Min, H. K.1993Negative correlation between the conversion of thyrotropin receptor-bound blocking type thyrotropin receptor antibody to the stimulating type by anti-human IgG antibodies and the biological activity of blocking type thyrotropin receptor antibody.
It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Korean Medical Science58355-360https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053714/
AntibodiesTSH receptor, TSAb, Tbab, Graves' disease, Atrophic thyroiditis, pregnancy, toxic adenoma, goiter, nodules3Orgiazzi, J.; Madec, A. M.1994[Thyroid-stimulating hormone receptor and thyroid diseases].
Since the description of the structure of the TSH receptor using molecular biology techniques, it has become possible to analyse the role of anomalies of this receptor in thyroid disorders. Implicated in the pathophysiology of Graves' disease by indirect observations, the autoantigenic role of the TSH receptor has now been clearly confirmed.
Nevertheless, the epitopes of the extracellular domain of the receptor corresponding to each type, stimulatory or epitopes of the extracellular domain of the receptor corresponding to each type, stimulatory or blocking, of anti-receptor toward activation or blocking.
The events that induce and maintain autoimmunization to the receptor remain hypothetical, but the possible existence of soluble forms of the receptor opens new perspectives.
In practice, however, assessment of TSH anti-receptor antibodies is useful in managing Graves' disease and in certain cases of primary myxoedema linked to the presence of blocking antibodies; it is mandatory in pregnant women for detection of foetal disease induced by maternal antibodies.
The responsibility of the receptor is sought in other thyroid diseases such as toxic adenoma, rare forms of nonimmunologic, familial hyperthyroidism, simple goiter, nodules and lack of response to TSH. Recently, a mutation mapped into the 3rd intracellular loop has been shown in toxic adenoma. Such discoveries are as important for physicians (and patients) as for cellular biologists.
La Revue du praticien9441184-1191http://search.proquest.com/docview/76769109/DCA54746475B491BPQ/1
Atrophic ThyroiditisHashimoto's, atrophic thyroiditis, T4 therapy, RAIU, iodine, growth, menstrual cycle, hypothyroidism, painless thyroiditis, euthyroid, remission, TBII3Okamura, K., Sato, K., Ikenoue, H., Nakagawa, M., Kuroda, T., Yoshinari, M., & Fujishima, M.1994Primary hypothyroidism manifested in childhood with special reference to various types of reversible hypothyroidism
The clinical course of 15 patients with overt primary hypothyroidism manifested in childhood were studied. Nine female patients with goitrous hypothyroidism due to chronic thyroiditis showed almost normal height and became euthyroid spontaneously during iodine restriction. The other 6 nongoitrous patients (3M and 3F) (atrophic thyroiditis in 2, lingual goiter in 2 and probable hypoplastic thyroid in 2) showed physical growth retardation and remained irreversibly hypothyroid requiring replacement therapy. In the reversible group, the characteristic findings were high thyroidal radioactive iodine uptake (58 +/- 19%/24 h, N = 8) and positive perchlorate discharge test. Serum nonhormonal iodine levels were high in 4 of 6 patients measured. During the long-term follow-up period of 6 years in 6 patients, 2 patients remained euthyroid with normal growth and regular menstrual cycle and 4 patients became hypothyroid again (after eating seaweed in 1, despite iodine restriction in 2 and after the episode of painless thyroiditis in 1). Transient retardation of growth was observed during the second episode of hypothyroidism. In the irreversible group, one patient with blocking type TSH binding inhibitor immunoglobulin (TBII) became thyrotoxic 4 years later with the decrease in activity of blocking type TBII. These results suggested that reversible recovery of the thyroid function could be expected in patients with juvenile hypothyroidism due to chronic thyroiditis after (1) iodine restriction, (2) improvement of immunological perturbation, or (3) disappearance of blocking type TBII. However, careful follow-up is necessary, because hypothyroidism would recur again with transient retardation of growth in children.
European Journal of Endocrinology,2131131–137.https://www.ncbi.nlm.nih.gov/pubmed/7915603Blocking TBII tested and variable in some
Atrophic ThyroiditisGenes, HLA, Korea, antibody3Chung, J. H.; Cho, B. Y.; Lee, H. K.; Kim, T. G.; Han, H.; Koh, C. S.1994The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody.
The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Korean Medical Science29155-161https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053953/
Thyroid volumeScintigraphy, TBII, TBAb, TSAb, TGAb, T4 therapy, hypothyroidism3Kasagi, K.; Hatabu, H.; Miyamoto, S.; Takeuchi, R.1994Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies
The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% +/- 12 (SD)%; normal < 11%] and for thyroid stimulation-blocking antibodies (TSBAbs) (90% +/- 9%: normal < 32%) were studied. Thyroid scanning was performed using technetium-99m or iodine-123, when the patients were hypothyroid. Analysis of the scan images revealed the presence of localized functioning areas in six patients (group 1), and no visualization of the thyroid in the remaining five patients (group 2). Patients in group 1 showed significantly higher uptake of 99mTc than those in group 2 (P < 0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% +/- 17%; normal < 145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases.
European journal of nuclear medicine921962
AntibodiesTBAb, hypothyroidism, family of cases, T4, TSH, TSAb, TGAb, Mabs, goiter3Uematsu-Yanagita, Motoko; Inoue, Daisuke; Koshiyama, Hiroyuki; Akamizu, Takashi1997Familial Clustering of Thyroid Stimulation-Blocking Antibody
Short article, full text here: Thyroid stimulation—blocking antibody (TSBAb), an antibody that blocks stimulation of thyroid adenylate cyclase induced by thyrotropin stimulation,1 has been considered to play some pathogenetic role in atrophic autoimmune primary hypothyroidism.2,3 We describe a familial clustering of TSBAb that affected 4 members of 1 family. We believe that these cases provide a novel mechanism of hereditary hypothyroidism. REPORT OF CASES. The proband, a 63-year-old woman, presented with general malaise and edema. Her goiter was not palpable. She was found to have hypothyroidism (free thyroxine, 4 pmol/L [0.3 ng/dL]; thyrotropin, 149 mU/L) and was positive for both thyrotropin receptor antibody (88.1%) and TSBAb (92.8%). Serologic tests were also positive for antithyroglobulin and antithyroid microsomal antibodies (X200 and X200). Her daughter, who had been diagnosed as having hypothyroidism with TSBAb (73.0%), had been treated with levothyroxine (100 μg/d) for several years. Her son had once been treated in another clinic under the diagnosis of hypothyroidism when he was in his 20s. However, he was currently euthyroid without taking any medication. He was also positive for TSBAb (70.4%). Furthermore, a son of the proband's daughter, i.e. a grandson of the prband, was found to be positive for TSBAb (78.0%), although he was euthyroid. Goiter was absent in all the members. To our knowledge, this is the first report about the familial occurrence of TSBAb, except for an article on transplacental passage of TSBAb, which causes neonatal transient hypothyroidism. It should be noted that there was considerable variation of clinical manifestation among the affected members: apparently irreversible hypothyroidism (the proband and her daughter), reversible hypothyroidism (her son), and euthyroidism (her grandson). These variations may be explained by the different epitopes of TSBAb.3 We believe that screening for TSBAb is meaningful in cases of familial hypothyroidism and that TSBAb should be added to the list of possible mechanisms of hereditary hypothyroidism.
Archives of Internal Medicine4157462-46410.1001/archinte.1997.00440250122019
Atrophic ThyroiditisH. pylori gastritis, Hashimoto's, Graves' disease, nontoxic multinodular goiter, Addison's, IgG3de Luis, D. A., Varela, C., de La Calle, H., Cantón, R., de Argila, C. M., San Roman, A. L., & Boixeda, D.1998Helicobacter pylori infection is markedly increased in patients with autoimmune atrophic thyroiditis
Infection by viral or bacterial pathogens has been suspected in playing a role in the development of autoimmune thyroid disease. Because Helicobacter pylori might be involved in the development of nongastrointestinal conditions such as rosacea, ischemic heart disease, and diabetes mellitus, we evaluated the prevalence of H. pylori infection in patients with autoimmune thyroid disease. Fifty-nine patients with autoimmune thyroid disease were included: autoimmune atrophic thyroiditis (n=21), Hashimoto's thyroiditis (n=18), and Graves' disease (n=20). Twenty patients with nontoxic multinodular goiter served as controls for nonautoimmune thyroid disease, and 11 patients with Addison's disease served as controls for nonthyroid endocrine autoimmune disease. The levels of anti-H. pylori immunoglobulin G (IgG) were determined, and a radiolabeled urea breath test were performed. The prevalence of H. pylori infection was markedly increased in the patients with autoimmune atrophic thyroiditis (85.7%), compared with the controls with nontoxic multinodular goiter (40%) and Addison's disease (45.4%). Infection by H. pylori resulted in increased levels of gastrin, pepsinogen I, and pepsinogen II in the H. pylori-positive groups, compared with the H. pylori-negative groups. A positive linear regression was found between the levels of microsomal autoantibodies and those of anti-H. pylori IgG in patients with autoimmune atrophic thyroiditis (n=21; r=0.79; p < 0.01). Finally, and although the overall prevalence of H. pylori infection was not increased, the anti-H. pylori IgG levels and the results from the breath test were higher in the patients with Graves' disease and Hashimoto's thyroiditis patients than in the controls. Clearly, the prevalence of H. pylori infection is increased in autoimmune atrophic thyroiditis and results in abnormalities of gastric secretory function. The strong relation between the levels of anti-H. pylori IgG and the levels of microsomal antibodies suggests that H. pylori antigens might be involved in the development of autoimmune atrophic thyroiditis or that autoimmune function in autoimmune atrophic thyroiditis may increase the likelihood of H. pylori infection.
Journal of Clinical Gastroenterology,426259–263.https://www.ncbi.nlm.nih.gov/pubmed/9649006
AntibodiesTBII, Hashimotos, Atrophic thyroiditis, T4 therapy, FT4, TSH, TSAb, 18 months, Thyroid volume, remission, euthyroidism3Khoo, D. H. C; Eng, P. H. K.; Ho, S. C.; Fok, A. C. K.1999Differences in the levels of TSH‐binding inhibitor immunoglobulins in goitrous and agoitrous autoimmune thyroiditis after twelve months of l‐thyroxine therapy
The aims were to study the prevalence of TSH binding inhibitor immunoglobulins (TBII) in newly diagnosed patients with autoimmune hypo-thyroidism, to determine if clinical and biochemical parameters in these patients differed, and to study the course of these antibodies after 12 months of L-thyroxine (LT4) therapy. In a prospective study, 111 consecutive patients with newly diagnosed auto-immune hypothyroidism were enrolled. Patients were divided into groups according to the presence or absence of a goitre and TBII levels. Clinical and biochemical differences in these patients were analysed. Patients were then treated with L-thyroxine (LT4) for 12 months and changes in their TBII monitored. Free T4 and TSH levels were measured at baseline and then 6-weekly during the titration of LT4 doses. Once TSH levels had normalized, these measurements were performed 3 monthly. TBII levels were measured in patients at baseline and 12 months. Thyroid stimulating blocking antibody (TSBAb) levels were measured 12-18 months after initiation of LT4 therapy. Twenty patients were TBII-positive, 10 goitrous and 10 agoitrous. Agoitrous TBII-positive patients were found to have similar characteristics: these included TBII levels > 100 U/l, potent thyroid stimulating blocking antibody (TSBAb) activity and a tendency for TBII levels to remain unchanged or to rise after LT4 therapy. The degree of hypothyroidism seen in these cases was significantly greater than in all other groups. In contrast, goitrous TBII-positive patients were heterogenous, most did not have significant TSBAb activity and TBII disappeared in 5 out of 10 cases after a year of LT4 treatment. While TBII disappeared in 6 of the 20 patients after a year, remission of hypothyroidism occurred in only 3 cases. The degree of hypothyroidism in agoitrous TSH-binding inhibitor immunoglobulins-positive patients appears to be more severe than that seen in other forms of AIT. The differences in thyroid stimulating blocking antiboby activity and response to LT4 therapy in agoitrous and goitrous autoimmune thyroiditis suggest that the TSH-binding inhibitor immunoglobulins in these patients are fundamentally different. The disappearance of TSH-binding inhibitor immunoglobulins in hypothyroid patients was not accompanied by the reversal of hypothyroidism in 50% of patients.
Clinical Endocrinology15173-7910.1046/j.1365-2265.1999.00740.x
AntibodiesTSAb, Tbab, Graves' disease, Hashimoto's, TPOAb, pregnancy, diagnosis, therapy3Orgiazzi, Jacques2000Anti-TSH Receptor Antibodies in Clinical Practice
Autoimmune thyroid diseases are the more prevalent organ-specific autoimmune disorders in humans. They encompass a wide spectrum of clinical presentations, with hyperthyroid Graves' disease at one end and atrophic myxedema at the other. Whether Graves' disease and lymphocytic thyroiditis represent different aspects of the same disease or different diseases remains unclear. Autoimmune thyroid diseases share common immunologic markers—mononuclear cell infiltration of the thyroid—and circulating antithyroid antibodies, the specificities of which might, in part, account for the diversity of these diseases. Autoantibodies against the thyroid-stimulating hormone receptor (TSH receptor antibodies, [TSHR-Ab]) represent only one family of thyroid autoantibodies. Others include antithyroperoxidase (TPO-Ab), the former antithyroid microsomal antibodies, antithyroglobulin, and the recently identified anti–sodium/iodide symporter antibodies. Historically, TSHR-Ab have been associated with hyperthyroid Graves' disease.90 Indeed, contrary to the other antithyroid antibodies, TSHR-Ab are pathogenic, capable of activating or blocking TSH receptor functions, as demonstrated by the occurrence of transplacentally transmitted hyperthyroidism or hypothyroidism in the fetus of mothers with high enough levels of circulating stimulating or blocking TSHR-Ab. Pathogenic antibodies could be viewed as the ideal marker for the diagnosis and management of the corresponding autoimmune disease. The various conditions discussed in this article that could benefit from the assay of TSHR-Ab include the following: Graves' disease TSHR-Ab at diagnosis of hyperthyroid Graves' disease Diagnostic valueSeverity markerAn aid to the choice of treatmentTSHR-Ab and the management of antithyroid drug (ATD) treatmentTSHR-Ab and ablative treatments Radioiodine treatmentSurgical treatmentSpecial conditions Graves' disease and pregnancyGraves' disease in children and adolescentsExtrathyroidal manifestations of Graves' diseaseGraves' disease and thyroid carcinomaAutoimmune hypothyroidism Prevalence of TSHR-Ab in autoimmune thyroiditisClinical usefulness of TSHR-Ab assays Transient transplacental neonatal hypothyroidismSpontaneous remission from autoimmune hypothyroidismAtypical thyroid autoimmune patterns Fluctuating thyroid functionHypothyroid Graves' diseasePainless thyroiditisOther conditions Iatrogenic thyroid disordersSubacute thyroiditisThyroid irradiation for toxic or nontoxic nodular goiter Depending on the clinical setting, the determination of either stimulating or blocking TSHR-Ab is discussed. The presence of TSHR-Ab is the hallmark of Graves' disease. Nevertheless, TSHR-Ab may be detected in other conditions, indicating the possible association of Graves' disease with other thyroid diseases.
Endocrinology and Metabolism Clinics of North America229339-35510.1016/S0889-8529(05)70135-3http://www.sciencedirect.com/science/article/pii/S0889852905701353
Atrophic ThyroiditisDermatitis herpetiformis, Hashimoto's, 41 patients, controls, Thyroid volume, T3, T4, sex,3Zettinig, Georg; Weissel, M.; Flores, J.; Dudczak, R.; Vogelsang, H.2000Dermatitis herpetiformis is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis
Background Dermatitis herpetiformis (DH) is a gluten-sensitive skin disease that is associated with a variety of autoimmune disorders. Several investigations demonstrated an association between DH and autoimmune thyroid disease. However, it has not been shown if DH is associated with atrophic or goitrous variant of Hashimoto's thyroiditis. Materials and methods We investigated a cohort of 41 DH patients (18 male, 23 female) and a control group (11 male, 19 female; sex and age matched healthy volunteers) to find out which variant of Hashimoto's thyroiditis is associated with DH. All patients had thyroid hormones and antibodies measured. In addition to that, thyroid sonography as well as detailed history-taking of previous thyroid disease were performed. Results In the control group no individual with elevated levels of thyroid antibodies nor abnormal thyroid hormones nor thyroid atrophy was found. Median thyroid volume in the control group was 11 mL (range 4.8–24.7 mL). However, in nine DH patients (22%) elevated levels of antithyroid microsomal (TM) antibodies were seen (P < 0.01). Three of them had abnormal thyroid hormones (7%). In the group of DH patients a significantly smaller thyroid volume was found (median 8 mL, range 1.6–25.2 mL; P < 0001). Thyroid atrophy (volume < 4.4 mL) was found in 10 DH patients (24%) of whom 9 were females. All patients with elevated levels of TM antibodies or abnormal thyroid hormones and all patients with a history of previous hypothyroidism had a thyroid volume < 7 mL. Goitrous variant of Hashimoto's thyroiditis was not seen in any of the DH patients. Conclusions Our findings demonstrate that DH is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis.
European Journal of Clinical Investigation13053-5710.1046/j.1365-2362.2000.00590.xhttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1046/j.1365-2362.2000.00590.x/abstract
Thyroid volumeHashimoto's, case study3Iwata, Masahiro; Kasagi, Kanji; Misaki, Takashi; Fujita, Toru2001Thyroid Hemilobar Atrophy in Patients Diagnosed as Having Hashimoto's Thyroiditis
case study. 63y male, mildly hypothyroid. Left thyroid lobe was slightly enlarged, and right was irregular and atrophied. Severe hemilobar atrophy is rare type of Hashimoto's.
AntibodiesStimulating, blocking, Graves' disease, therapy3Cho, Bo Youn2002Clinical applications of TSH receptor antibodies in thyroid diseases.
The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical implications, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.
Journal of Korean Medical Science317293-301https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3054886/
Atrophic ThyroiditisHepatitis, atrophic gastritis, Addison's, pancreas, autoimmunity3Bergwitz, C.; Brabant, G.; Trautwein, C.; Manns, M. P.2002A patient with autoimmune hepatitis type I, Addison's disease, atrophic thyroiditis, atrophic gastritis, exocrine pancreatic insufficiency, and heterozygous alpha1-antitrypsin deficiency
This report describes a 60-yr-old white male presenting with decompensated liver cirrhosis. He had a history of Addison's disease for 36 yr, primary hypothyroidism for 5 yr, and moderate alcohol consumption. His laboratory studies and a liver biopsy supported the diagnosis of autoimmune hepatitis. Furthermore, he was found to be heterozygous for the piZ allele of the alpha1-antitrypsin gene with normal serum alpha1-antitrypsin levels and absence of pulmonary affection. Mucosal biopsies revealed moderately severe atrophic gastritis; however, signs of pernicious anemia were missing. An association of autoimmune hepatitis with endocrine disorders and atrophic gastritis has been described. Long term hydrocortisone therapy for his adrenal insufficiency may have prevented a faster course of the liver disease, whereas the heterozygous alpha1-antitrypsin deficiency and moderate alcohol consumption constituted additional risk factors ultimately leading to the development of cirrhosis.
The American journal of gastroenterology4971050
AntibodiesPregnancy3Amino, Nobuyuki; Izumi, Yukiko; Hidaka, Yoh; Takeoka, Keiko; Nakata, Yukiko; Tatsumi, Ke-Ita; Nagata, Atsuo; Takano, Toru2003No Increase of Blocking Type Anti-Thyrotropin Receptor Antibodies During Pregnancy in Patients with Graves’ Disease
Serial changes in serum levels of anti-TSH receptor antibodies were examined during and after pregnancy in six patients with Graves’ disease receiving no or minimal maintenance doses of antithyroid drugs. During pregnancy, serum levels of TSH-binding inhibitory Igs (P < 0.001) and thyroid-stimulating antibodies (TSAbs) (P < 0.01) decreased gradually but increased after delivery in all patients. Activities of thyroid-stimulation blocking antibodies (TSBAbs) were lower than the cut-off value in early pregnancy, and values significantly decreased in four patients during pregnancy. The other two patients showed no significant change during pregnancy. In contrast, TSBAb levels increased significantly (P < 0.01) after delivery in all patients. We found that activities of TSH-binding inhibitory Igs, TSAb, and TSBAb decrease during pregnancy and increase after delivery, suggesting that amelioration of Graves’ disease during pregnancy is induced by decrease of TSAb but not by the appearance of TSBAb.
The Journal of Clinical Endocrinology & Metabolism12885871–587410.1210/jc.2003-030971
AntibodiesGraves' eye disease, euthyroid, Hashmoto's, Atrophic thyroiditis, case study, TPOAb, TGAb3Tamagno, G.; De Carlo, E.; Betterle, C.; Murialdo, G.2004Graves’ ophthalmopathy and atrophic thyroiditis: A case report
Graves’ ophthalmopathy (GO) — also known as thyroid-associated orbitopathy or ophthalmopathy — usually affects patients with Graves’ disease. Antibodies stimulating the TSH receptor are thought to be involved in the pathogenesis of this important and disabling extra-thyroidal manifestation of Graves’ disease. Less frequently, GO occurs in subjects who neither have nor have ever shown evidence of thyroid dysfunction (“euthyroid GO”), while the occurrence of GO in patients with autoimmune Hashimoto’s thyroiditis is thought to be quite rare and has sporadically been reported. The late and abrupt occurrence of severe GO without hyperthyroidism in an 88-yr-old woman with primary myxedema due to atrophic thyroiditis must be considered as an exceptional event. In this patient, GO was combined with elevated titres of serum auto-antibodies directed against the TSH receptor, while serum levels of anti-thyroglobulin and thyroperoxidase antibodies were within the normal range or only occasionally slightly above the normal values.
Journal of Endocrinological Investigation227163-16610.1007/BF03346262
Atrophic Thyroiditiscase, height, bone age, pituitary hyperplasia, T3, T4, TSH, fibrosis, T4 therapy3Kagawa, J., Asakura, I., Shimizu, N., Hibino, K., Ito, M., & Ikegaya, T.2004The long-term effect of replacement therapy in a short girl with autoimmune atrophic thyroiditis of prepubertal onset
A 9 yr 11 mo old girl was admitted to our hospital because of short stature. Her growth rate gradually decreased and her height was 120 cm (-2.5 SD) on admission. The mother's and father's heights were 157 cm (-0.2 SD) and 163 cm (-1.3 SD), respectively. Her bone age was retarded (6 yr 10 mo). An MRI indicated pituitary enlargement, which mimicked adenoma. Evaluation of the pituitary-thyroid axis and thyroid function proved she had primary hypothyroidism (T3 0.5 ng/ml, T4 1.0 μg/dl, TSH 1,030 μU/ml). These findings, thyroid autoantibody (anti-microsome antibody 400 xs) and histopathology (moderate fibrosis and mild lymphocytic infiltration) suggested acquired hypothyroidism due to autoimmune atrophic thyroiditis of prepubertal onset. Since the evaluation, she has been treated with levothyroxine. The pituitary enlargement disappeared within 3 mo after levothyroxine replacement. The growth rate increased and her height reached 153.2 cm (-1.0 SD) during 10 yr replacement (at 19 yr 11 mo of age). An improvement in her final height was obtained by long-term thyroid hormone replacement therapy. Enough endocrinological study and repeated MRI evaluation are necessary in cases of pituitary enlargement which mimics adenoma before considering surgery.
Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations113https://doi.org/10.1297/cpe.13.33https://www.ncbi.nlm.nih.gov/pubmed/24790295
AntibodiesAtrophic thyroiditis, Hashimoto's, Thyroid volume, nodules, TSH, subclinical, TPOAb, TGAb, FT3, FT43Bülow Pedersen, I., Laurberg, P., Knudsen, N., Jørgensen, T., Perrild, H., Ovesen, L., & Rasmussen, L. B.2005A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure
OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism.
DESIGN:A population study including 4649 randomly selected subjects.
MEASUREMENTS: Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4.
RESULTS: Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23).
CONCLUSION: We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.
Clinical Endocrinology662713–720https://doi.org/10.1111/j.1365-2265.2005.02284.x
AntibodiesSarcoidosis, hypothyroidism, TBAb, case3Schmidt, J.; Capoen, J. -P.; Kyndt, X.; André, L.; Fleury, D.; Vanhille, P.2009Sarcoidosis associated with hypothyroidism due to thyrotropin-receptor blocking antibodies / Syndrome de Löfgren associé à une hypothyroïdie par anticorps bloquant les récepteurs de la TSH
See fulltext in NOTES. Abstract The association of sarcoidosis and auto-immune thyroid disease has been reported. We report a 29-year-old woman, treated for hypothyroidism caused by thyrotropin-receptor blocking antibodies, who developed a sarcoidosis (Löfgren’s syndrome). Auto-immune thyroid diseases and sarcoidosis could share common pathogenic mechanisms. Résumé L’association sarcoïdose et pathologie thyroïdienne auto-immune semble être plus que fortuite. Nous rapportons le cas d’une patiente suivie pour maladie de Basedow avec des anticorps de variété bloquante entraînant une hypothyroïdie qui développe secondairement un syndrome de Löfgren. Des mécanismes immunitaires communs pourraient être à l’origine de ces deux pathologies rares.
La Revue de Médecine Interne730628-62910.1016/j.revmed.2008.08.022http://www.sciencedirect.com/science/article/pii/S0248866308008357
AntibodiesCase, high TSH3Azzopardi, Peter; Forrester, Mike; Ehtisham, Sarah2010Three siblings with self‐resolving congenital hyperthyrotropinaemia secondary to thyrotropin receptor blocking antibodies
Thyrotropin receptor blocking antibodies are a rare cause of hyperthyrotropinaemia and more rarely of congenital hypothyroidism. We report a case of hyperthyrotropinaemia but normal thyroid hormone in the newborn of a mother with hypothyroidism treated with thyroxine. Two older siblings had similar high thyrotropin and normal thyroid function in the newborn period which did not require hormone treatment and resolved spontaneously. Demonstration of thyrotropin receptor antibodies in the child confirmed our diagnosis. Our case was not treated with thyroid replacement hormone and has remained biochemically euthyroid, with thyrotropin levels returning to normal over a period of months.
Journal of Paediatrics and Child Health7‐846439–44110.1111/j.1440-1754.2009.01687.x
Atrophic ThyroiditisTBAB, TPOAb, TSH, FT3, FT4, scintigraphy, pituitary hyperplasia, T4 therapy, hypothyroidism3Inamo, Y.2011A 5-year-old boy with atrophic autoimmune thyroiditis caused by thyroid-stimulation blocking antibodies.
A 5-year-old boy was presented for a growth disturbance, which was initially noted at 3 years of age. Endocrinological testing identified severe hypothyroidism, defined by the following levels:
TSH 990.5 microU/mL, F-T3 0.26 pg/mL, and F-T4 0.09 ng/dL.
Serum anti-thyroid peroxidase (TPO) antibodies were 158 IU/mL and serum thyroid-stimulation blocking antibodies (TSBab) levels were 82.1 IU/mL (normal range < 45.6). Thyroid scintigraphy with 99mTc showed markedly decreased uptake, and magnetic resonance imaging (MRI) revealed pituitary hyperplasia.
He was diagnosed with atrophic autoimmune thyroiditis. His thyroid function and pituitary size normalized following thyroid hormone replacement therapy.
We report a rare case of a young boy with atrophic thyroiditis caused by TSBab.
Journal of Pediatric Endocrinology & Metabolism724591–594.
AntibodiesGraves' eye disease, hypothyroidism, Thyroid volume, TSH, FT4, TPOAb, TGAb, T4 therapy, TSAb3Seoane Cruz, Inés; Penín Álvarez, Manuel; Rodríguez Ferro, Fátima; Luna Cano, Reyes2012Unilateral exophthalmos and hypothyroidism
Orbital masses and thyroid ophthalmopathy are the most prevalent causes of uniocular proptosis. We report the case of a female patient with worsening of a prior unilateral proptosis due to an associated thyroid ophthalmopathy (TO). A 41-year-old female patient with primary hypothyroidism and a congenital staphyloma in her left eye reported a worsening of proptosis and left retro-orbital pain over the previous weeks. A physical examination confirmed a unilateral exophthalmos and ruled out edema or signs of conjunctival inflammation in either eye. The patient had goiter, which could be palpated but was not visible even in the extended neck. There were no adjacent adenopathies. Ultrasound examination revealed a heterogeneous gland with no nodules. The left lobe was 3.7 cm × 2.0 cm × 1.3 cm in size, and the right lobe 3.6 cm × 1.5 cm × 1.2 cm in size. Blood tests performed some weeks previously had shown subclinical autoimmune hypothyroidism: TSH 10,337 μIU/mL (0.3–4.5), free T4 1.04 ng/100 mL (0.7–2), antiperoxidase antibodies 817 IU/mL (0.0–35), antithyroglobulin antibodies 59.4 IU/mL (0–40). This condition was being treated with levothyroxine 75 mcg/day. An orbital CT scan was performed to rule out the presence of a mass, and it showed the increase in diameter of the left eyeball which is characteristic of staphyloma and a mild to moderate bilateral thickening of the extraocular muscles (Fig. 1) suggesting thyroid ophthalmopathy. Anti-TSH receptor antibody level was 27.5 U/L (0–10).
Endocrinología y Nutrición (English Edition)359217-21810.1016/j.endoen.2011.09.006http://www.sciencedirect.com/science/article/pii/S2173509312000517
TSHGraves' disease, TBAb, TSAb, Hyper-hypo3Dietrich, J. W., Landgrafe, G., & Fotiadou, E. H.2012TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis.
This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range. 4.3. Thyrotropin Receptor Antibodies -- Classical Graves' disease (autoimmune thyroiditis type 3A) is caused by formation of stimulating TSH receptor antibodies (sTRAbs, also referred to as thyroid stimulating antibodies, TSAbs) by intrathyroidal B cells with resulting hyperthyroidism. Retroorbital TRAb formation leads to endocrine ophthalmopathy, and it is assumed that other manifestations of Graves' disease derive from extrathyroidal TRAb effects, too.
As mentioned above sTRAbs may suppress TSH secretion independently from FT4 levels by activation of the Brokken-Wiersinga-Prummel loop [47]. Therefore, in Graves' disease low TSH levels may persist despite even low FT4 levels [50]. Obviously, this also applies to children born to mothers with Graves's disease and high antibody load [41]. Immunogenic TSH suppression may complicate diagnosis of thyroid status and dosage of thyroid hormones or thyrostatic agents in Graves' disease.
Inhibiting TSH receptor autoantibodies (iTRAbs, or TSH-stimulation blocking antibodies, TSBAbs) block signal transduction at the TSH receptor. Up to now, their effect on global thyroid homeostasis or ultrashort loop control of TSH secretion has not been investigated, which may also be a consequence of still limited availability of reliable sTRAb and iTRAb assays for routine use. Over the time, the proportion of stimulating or inhibiting TRAbs may change in individual patients [342].
Journal of Thyroid Researchhttps://doi.org/10.1155/2012/351864
AntibodiesGraves, diagnosis, treatment3Barbesino, Giuseppe; Tomer, Yaron2013Clinical Utility of TSH Receptor Antibodies
Context:TSH receptor antibodies (TRAb) cause Graves' disease (GD) hyperthyroidism. Widely available TRAb measurement methods have been significantly improved recently. However, the role of TRAb measurement in the differential diagnosis of hyperthyroidism, the prediction of remission of GD hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the clinical assessment of Graves' ophthalmopathy (GO) are controversial.Evidence Acquisition:We reviewed and analyzed the literature reporting primary data on the clinical use of TRAb. We focused our analyses on clinical studies analyzing third-generation TRAb assays.Evidence Synthesis:The performance of TRAb in the differential diagnosis of overt hyperthyroidism is excellent, with sensitivity and specificity in the upper 90%. TRAb can accurately predict short-term relapses of hyperthyroidism after a course of antithyroid drugs but are less effective in predicting long-term relapses or remissions. Pregnancies in women with GD with negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas high titers of TRAb in pregnancy require careful fetal monitoring. GD patients with GO frequently have high TRAb levels. However, there are insufficient data to use the test to predict the clinical course of GO and response to treatment.Conclusions:Third-generation TRAb assays are suitable in the differential diagnosis of hyperthyroidism. In GD, TRAb should be tested before deciding whether methimazole can be stopped. TRAb should be used in pregnant women with GD to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires further studies.
The Journal of Clinical Endocrinology & Metabolism6982247-225510.1210/jc.2012-4309https://academic-oup-com.ezproxy.lib.ucalgary.ca/jcem/article/98/6/2247/2536939
AntibodiesTRAb, eye disease, Graves, TBII, TSI, assays3Jang, Sun Young; Shin, Dong Yeob; Lee, Eun Jig; Choi, Young Joon; Lee, Sang Yeul; Yoon, Jin Sook2013Correlation between TSH Receptor Antibody Assays and Clinical Manifestations of Graves' Orbitopathy
[stimulating antibody] Purpose To investigate an association between the levels of serum thyroid-stimulating hormone (TSH)-receptor autoantibodies (TRAbs) and Graves' orbitopathy (GO) activity/severity scores, and compare the performance of three different TRAb assays in assessing the clinical manifestations of GO. Materials and Methods Cross-sectional study. Medical records of 155 patients diagnosed with GO between January 2008 and December 2010 were reviewed. GO activity was assessed by clinical activity score (CAS) and severity graded with the modified NOSPECS score by a single observer. Serum TRAb was measured by three different methods: 1st generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay (TRAb1st); 3rd generation TBII assay (TRAb3rd); and biological quantitative assay of thyroid-stimulating immunoglobulin (TSI) using Mc4-CHO cells (Mc4-CHO TSI assay). Results were correlated with scores of activity/severity of thyroid eye disease. Results All three assays (TRAb1st, TRAb3rd, and Mc4-CHO TSI) yielded results that were significantly positively correlated with CAS (β=0.21, 0.21, and 0.46, respectively; p<0.05) and proptosis (β=0.38, 0.34, and 0.33, respectively; p<0.05). Mc4-CHO TSI bioassay results were significantly positively correlated with all GO severity indices (soft tissue involvement, proptosis, extraocular muscle involvement, and total eye score; β=0.31, 0.33, 0.25, and 0.39, respectively; p<0.05). Conclusion Mc4-CHO TSI bioassay was superior over the two TBIIs in assessing active inflammation and muscle restriction due to GO, whereas TBII assay would be sufficient for evaluation of patients with proptosis.
Yonsei Medical Journal4541033-103910.3349/ymj.2013.54.4.1033https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663223/
Atrophic ThyroiditisHypertension, heart disease3Bastenie, P. A.; Ermans, A. M.2013Atrophic Thyroiditis, Hypertension and Coronary Heart Diseasebook chapterThyroiditis and Thyroid Function: Clinical, Morphological, and Physiopathological Studies
Atrophic ThyroiditisFacial palsy, case, TSH, T4, T3, FT4, TPOAb, Tgab, TRAb, thyroid volume, vascularity, scintigraphy, pituitary hypertrophy3Lee, Hyung Jik; Kim, Jin Kyung2013Nongoitrous autoimmune thyroiditis with facial palsy
We report a case of severe hypothyroidism with nongoitrous, autoimmune thyroiditis and pituitary hyperplasia in a 13-year-old boy, who presented with sudden palsy on the left side of his face. Prednisolone and antiviral medication was administered. However, the facial palsy did not improve completely. The medications were replaced with thyroxine, and the facial palsy recovered. Endocrinological testing showed severe hypothyroidism as follows: thyroid stimulating hormone (TSH) level >100 µIU/mL, T4 of 1.04 µg/dL, T3 of 0.31 ng/mL, and free T4 of 0.07 ng/dL. Level of serum antithyroid peroxidase antibodies was 1,933.39 IU/mL, and that of antithyroglobulin antibodies was 848.16 IU/mL. Level of TSH receptor antibodies was >40 IU/L. Bioassay result for TSH receptor stimulating antibodies was negative. Thyroid sonography revealed no increase in the size or vascularity of the bilateral gland. Thyroid scintigraphy with 99mTc showed decreased uptake, and magnetic resonance imaging demonstrated an enlarged pituitary gland.
Annals of Pediatric Endocrinology & Metabolism41821410.6065/apem.2013.18.4.214
Thyroid volumeThyroid cancer, biopsy, TSH, nodules, gender, age3Duran, Ayse Ocak; Anil, Cuneyd; Gursoy, Alptekin; Nar, Aslı2014The relationship between thyroid volume and malignant thyroid disease
The present retrospective study aimed to investigate the relationship between thyroid volume and prevalence of thyroid cancer. We investigated the data of 3,850 patients who underwent fine-needle aspiration biopsy (FNAB). Biopsy results were evaluated as diagnostic or nondiagnostic, and diagnostic results were classified as benign, malignant, and indeterminate. We included 2,672 patients who underwent FNAB firstly in our hospital and evaluated as diagnostic biopsy except subgroup of indeterminate. We obtained cytologic data, levels of serum thyroid-stimulating hormone (TSH), and thyroid volumes of those patients retrospectively. Among 2,672 patients with thyroid nodule, 2,562 (95.9 %) patients had benign cytology and 110 (%4,1) patients had malignant cytology. There was no correlation between the malignancy and gender (p = 0.935), and patients with malignant cytology were younger (52 vs 59, p < 0.001). Also, TSH levels were higher in patients with malignant than benign cytology (p = 0.017). Median volume of right part, left part, and total thyroid for patients who had malignant cytology was significantly lower than patients who had benign cytology (8.3, 7.1, 15.9 vs 10.8 ml, 9.0 mml, 20.6 ml, respectively, p ≤ 0.001 for all parameters). The results demonstrated that thyroid cancer prevalence was higher in patients with low thyroid volume. According to our results, thyroid volume should be considered as a risk factor for malignancy in the evaluation of thyroid nodules.
Medical Oncology13104-Jan10.1007/s12032-013-0814-2
AntibodiesGraves', TBAb, TSAb, cleavage, neutral, thyroid apoptosis,3Morshed, S. A.; Davies, T. F.2015Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies
The immunologic processes involved in Graves' disease (GD) have one unique characteristic – the autoantibodies to the TSH receptor (TSHR) – which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called “neutral” antibodies and which we now characterize as autoantibodies to the “cleavage” region of the TSHR ectodomain.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme1047727-73410.1055/s-0035-1559633http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047290/
Antibodiestesting, Graves, prognosis, remission, 12 months3Hwang, Sena; Shin, Dong Yeob; Song, Mi Kyung; Lee, Eun Jig2015High cut-off value of a chimeric TSH receptor (Mc4)-based bioassay may improve prediction of relapse in Graves’ disease for 12 months
There are scarce reports regarding a functional prognostic value of thyroid-stimulating autoantibody (TSAb) levels using a thyroid-stimulating hormone receptor chimera (Mc4) in Graves’ disease (GD) in iodine sufficient area. The aim of this study was to investigate whether Mc4-TSAb can predict GD remission/relapse after antithyroid drug (ATD) treatment and to compare Mc4-TSAb with a binding assay using M22 monoclonal antibody (M22-TRAb) in GD patients. We retrospectively reviewed the results of M22-TRAb and Mc4-TSAb in GD patients treated with ATD for 12 months. GD patients who underwent ATD treatment for at least 12 months were included. We compared the predictive values of M22-TRAb and Mc4-TSAb for GD remission and relapse. Of the 92 patients, 60 (65.2 %) achieved remission and 32 (34.8 %) relapsed within 12 months. In receiver operating characteristic analysis, there were no significant differences in the area under the curves (AUCs) between Mc4-TSAb [AUC = 0.79 (95 % CI 0.69–0.89)] and M22-TRAb [AUC = 0.69 (95 % CI 0.58–0.81)]. The optimal predictive cut-off values of M22-TRAb and Mc4-TSAb were 2.23 IU/L and 230 %, respectively. At a high Mc4-TSAb cut-off, the better specificity of 85.0 % and positive predictive value (PPV) of 69.0 % were shown compared with those at the best cut-off for M22-TRAb. In conclusion, a high cut-off for an Mc4 assay may improve the predictive value of relapse with superior specificity and PPV compared with M22-TRAb in treated GD.
AntibodiesGraves, bone turnover, therapy3Cho, Sun Wook; Bae, Jae Hyun; Noh, Gyeong Woon; Kim, Ye An; Moon, Min Kyong; Park, Kyoung Un; Song, Junghan; Yi, Ka Hee; Park, Do Joon; Chung, June-Key; Cho, Bo Youn; Park, Young Joo2015The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves’ Disease
Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease.
PLOS ONE1210e014459910.1371/journal.pone.0144599http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144599
AntibodiesTSAb, TBAb, Graves' eye disease,3Kampmann, E.; Diana, T.; Kanitz, M.; Hoppe, D.; Kahaly, G. J.2015Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study
The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO). Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb) and blocking (TBAb) antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage of specimen-to-reference ratio (SRR %). Blocking activity is defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone. All 101 consecutively followed-up patients with severe and active TAO were TBAb negative. In contrast, 91 (90%) were TSAb positive of whom 90 had Graves' disease. Serum TSAb levels correlated with the diplopia score (P = 0.016), total severity eye score (P = 0.009), proptosis (P = 0.007), lid aperture (P = 0.003), upper lid retraction (P = 0.006), keratopathy (P = 0.04), and thyroid binding inhibiting immunoglobulins (TBII, P < 0.001) and negatively with the duration of TAO (P = 0.002). Median serum values of TSAb were SRR% 418 (range 28% to 795%). TSAb, not TBAb, are highly prevalent in severe/active TAO and serum TSAb levels correlate with clinical disease severity.
International Journal of Endocrinology201510.1155/2015/678194https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499387/
Thyroid volumeCase3Altay, Mustafa; Colbay, Mehmet; Toruner, Fusun; Akturk, Mujde; Sencar, Erkam; Cakir, Nuri; Arslan, Metin2015An unusual organ involvement in a case of Werner Syndrome: thyroid atrophy
Werner Syndrome (WS) is a premature aging disease that begins in adolescence or early adulthood and results in the appearance of old age by 30-40 years of age. Some endocrinological abnormalities were manifested in this rare disease, such as hypogonadism, diabetes mellitus, hyperlipidemia. In this article, we present a nineteen years-old female patient who had been diagnosed as WS two years ago because of type 2 diabetes mellitus, osteopenia, hyperlipidemia, cataract, gray hair, and skin atrophy. Subclinical hypothyroidism was detected at her laboratory tests. Thyroid ultrasonography (USG) showed thyroid atrophy. Fine needle aspiration biopsy of both lobes confirmed this diagnose and excluded some infiltrative diseases such as amyloidosis. It should be kept in mind that thyroid atrophy could be seen in WS and, therefore, detailed thyroid examination including thyroid USG and close follow up should be performed in all patients with WS.
Çağdaş Tıp Dergisi25144-146https://doaj.org
Thyroid volumeMental health, TSH, FT3, FT4, Tokyo, schizophrenia, depression, bipolor, neurosis, mood disorders, anxiety, antobodies, TPO, TRAb,3Hamasaki, Hidetaka; Kakei, Masafumi; Yanai, Hidekatsu2015Thyroid Gland Volume Is Significantly Smaller in Patients With Psychiatric Disorders Than in Those Without Psychiatric Disorders
[FULL TEXT:] To the Editor: The thyroid gland normally secretes thyroxine and triiodothyronine. A previous study reported that partial substitution of triiodothyronine for thyroxine improved mood and neuropsychological functions in hypothyroid patients treated with only thyroxine,1 suggesting an importance of the integrity of the thyroid gland for neuropsychological functions. It is clear that thyroid hormone plays an important role in the brain, influencing mood and cognition; however, the detail mechanisms remain to be elucidated. Here, we investigated the differences of thyroid gland volume, thyroid hormones, and thyroid autoantibodies between individuals with and without psychiatric disorders. Method. The study protocol was approved by the Medical Ethics Committee of the National Center for Global Health and Medicine, Tokyo. Of 282 patients who had thyroid ultrasonography between October 2011 and December 2013, we investigated 239 subjects retrospectively. We excluded subjects with autoimmune thyroid diseases and thyroid carcinoma and patients taking lithium. Eighty-one subjects were diagnosed as having psychiatric disorders including schizophrenia (35%), depression (19%), bipolar disorder (7%), neurosis (5%), anxiety disorder (11%), and mood disorders (23%) per DSM-IV criteria by psychiatrists. We measured serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) by chemiluminescent enzyme immunoassay (Lumipulse Presto, Fujirebio Inc, Tokyo, Japan). We also measured serum levels of antithyroglobulin antibodies, antithyroid peroxidase antibodies, and TSH receptor antibodies by electrochemiluminescence immunoassay (ECLusys Anti-Tg, Anti-TPO and TRAb, Roche Diagnostics KK, Tokyo, Japan). Thyroid gland volume was determined by ultrasonography for each lobe individually using Brunn’s formula: 0.479 × length × depth × width.2 Figure 1 Click figure to enlarge Results. Thyroid gland volume of patients with psychiatric disorders was significantly smaller than that of individuals without psychiatric disorders (mean ± SD = 11.1 ± 9.3 mL vs 12.5 ± 7.1 mL, P = .005, Mann-Whitney U test) (Figure 1). There were no differences in serum levels of TSH, FT3, and FT4 and positivity for thyroid autoantibodies between individuals with and without psychiatric disorders. Observational epidemiologic studies reported a positive correlation of thyroid volume with body weight, body mass index, and body surface area.3 However, we did not observe significant differences in these anthropometric measurements between the 2 groups. Thyroid gland volume was not correlated with the duration of psychiatric disorders. Among physiologic factors that influence the thyroid gland volume,3,4 only age was significantly lower in patients with psychiatric disorders (50.5 ± 17.4 years, P < .001) compared with individuals without psychiatric disorders (63.7 ± 16.6 years). According to previous studies showing an inverse correlation between thyroid gland volume and age,3 our patients with psychiatric disorders showed remarkably smaller thyroid gland volume compared with individuals without psychiatric disorders for their age. Charlier et al5 studied a correlation between suicide risk and the weight of the thyroid gland by investigating 576 autopsies, including 299 cases of completed suicide. They found that thyroid weight was significantly smaller in cases of suicide compared with those who died of other causes.5 To take their and our results into consideration, the thyroid gland volume may affect the development and severity of mood and psychiatric disorders. However, several limitations should be considered. Selection bias might have occurred in the present study, and the potential confounding factors including medications might have affected the thyroid gland volume. We cannot explain the underlying mechanisms for the association between thyroid gland volume and psychiatric disorders by the present study. Further studies will be needed to elucidate the association of thyroid gland with psychiatric disorders. References 1. Bunevicius R, Kazanavicius G, Zalinkevicius R, et al. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med. 1999;340(6):424–429. PubMed doi:10.1056/NEJM199902113400603 Show Abstract 2. Brunn J, Block U, Ruf G, et al. Volumetric analysis of thyroid lobes by real-time ultrasound (author’s transl) [in German]. Dtsch Med Wochenschr. 1981;106(41):1338–1340. PubMed doi:10.1055/s-2008-1070506 Show Abstract 3. Barrère X, Valeix P, Preziosi P, et al. Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort. Clin Endocrinol (Oxf). 2000;52(3):273–278. PubMed doi:10.1046/j.1365-2265.2000.00939.x Show Abstract 4. Lee DH, Cho KJ, Sun DI, et al. Thyroid dimensions of Korean adults on routine neck computed tomography and its relationship to age, sex, and body size. Surg Radiol Anat. 2006;28(1):25–32. PubMed doi:10.1007/s00276-005-0042-3 Show Abstract 5. Charlier P, Watier L, Ménétrier M, et al. Is suicide risk correlated to thyroid weight? Med Hypotheses. 2012;79(2):264–266. PubMed doi:10.1016/j.mehy.2012.05.005 Show Abstract
The primary care companion for CNS disorders417
Thyroid volumestats, sex, age, Cuba, body surface area, smoking, blood type, thyroid cancer risk3Turcios, Silvia; Lence-Anta, Juan J.; Santana, Jose-Luis; Pereda, Celia M.; Velasco, Milagros; Chappe, Mae; Infante, Idalmis; Bustillo, Marlene; García, Anabel; Clero, Enora; Maillard, Stephane; Rodriguez, Regla; Xhaard, Constance; Ren, Yan; Rubino, Carole; Ortiz, Rosa M.; de Vathaire, Florent2015Thyroid Volume and Its Relation to Anthropometric Measures in a Healthy Cuban Population
Objectives The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. Study Design Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. Results The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. Conclusion Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit.
European Thyroid Journal1455-6110.1159/000371346https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404892/
AntibodiesTesting3Bitcon, V.; Donnelly, J.; Kiaei, D.2016Sensitivity of assays for TSH-receptor antibodiesSee full letter in notes.Journal of Endocrinological Investigation10391195-119610.1007/s40618-016-0520-yhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025503/
Atrophic ThyroiditisGH deficiency, height deficit, development, FT3, FT4, TSH, TSAb, TGAb, TPOAb3Otsuka, T., Tajima, N., Nagasaki, K., & Okazaki, M2016Successful Combined Treatment for Atrophic Thyroiditis With Growth Hormone Deficiency
Persons with untreated atrophic thyroiditis develop a permanent height deficit. Adequate thyroxine replacement therapy can improve growth and the probability of attaining normal adult height. However, height deficit is related to duration of thyroxine deficiency, regardless of the adequacy of thyroxine replacement therapy after diagnosis.1 Several studies reported that use of adjunctive therapy with growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) to improve the final height of patients.2-5 The rationale for this therapy is to prolong the growth period by inhibiting pubertal progression and delaying epiphyseal fusion,6 although GH deficiency in atrophic thyroiditis patients usually improves after L-thyroxine treatment.
We report a case of autoimmune atrophic thyroiditis in a boy who presented with GH deficiency even after his enlarged pituitary gland had decreased in size. Combined treatment with GH, GnRHa, and L-thyroxine was successful in allowing the patient to attain normal adult height. An 8-year-old boy presented with short stature at our hospital. Growth data were plotted on Japanese growth charts for males aged 0 to 18 years (V-Link Co, Ltd, Tokyo, Japan). The heights of his father and mother were 173 cm (+0.4 SD) and 154 cm (−0.8 SD), respectively. Mid-parental target height ([paternal + maternal heights +13]/2) was 170 cm. His height at the first visit was 110 cm (−2.9 SD; see Figure 1). Magnetic resonance imaging showed pituitary enlargement. Evaluation of serum hormone levels showed primary hypothyroidism and GH deficiency. Serum free T3 was 2.20 pg/mL (2.2-4.1 pg/mL), free T4 was 0.12 ng/dL (0.8-1.9 ng/dL), thyroid-stimulating hormone (TSH) was >1230 µIU/mL (normal range = 0.4-4.0 µIU/mL), and the peak value of GH in response to insulin was 1.4 ng/mL. Anti-TSH receptor antibody was elevated, at 25.5% (<10%), while antithyroglobulin antibody and antithyroid peroxidase antibody levels were normal.
Global Pediatric Health3https://doi.org/10.1177/2333794X16670082
Atrophic ThyroiditisPlummer's nails, TSAB, hypothyroidism, case, TSH,3Takasu, Nobuyuki; Seki, Hiromichi2018Plummer's Nails (Onycholysis) in a Thyroid-Stimulation-Blocking Antibody (TSBAb)-Positive Patient with Hypothyroidism
A 46-year old woman presented with symptoms and signs of hypothyroidism, including bradycardia and delayed reflexes. She had fingernail changes that were consistent with oncholysis (Plummer's nails) (Picture). She had TSBAb (thyroid-stimulation-blocking antibody)-positive hypothyroidism (TSBAb 87%, serum TSH 76mIU/L. The patient’s fingernails had the characteristic appearance of Plummer’s nails, a condition first described by Plummer in a patient with hyperthyroidism (1). Onycholysis, a condition in which the distal nail body separates from the nail bed, commonly occurs on the fourth fingers (Picture). Onycholysis has been said to be seen in patients with Graves’ hyperthyroidism. However, onycholysis is not specific to thyrotoxicosis. The differential diagnoses of onycholysis, which include psoriatic arthritis, lung cancer, sarcoidosis, bronchiectasis, and chronic arthritis, were all ruled out. Fungal infections were not observed in the nails. Paradoxically, onycholysis can also occur in patients with hypothyroidism (2). Plummer’s nails (onycholysis) were seen in a TSBAb-positive patient with hypothyroidism.
Internal medicine (Tokyo, Japan)0advpub10.2169/internalmedicine.0809-18
Atrophic ThyroiditisIodine, cholesterol, hypothyroidism4GREENE, ARTHUR M.1941Iodine and cholesterol metabolisms in patients with primary myxedema: A clinical and experimental study with a report of results of treatment
The clinical signs and symptoms of myxedema are well known. However, prior to the last decade too little attention was directed to the biochemical processes of the disease. Hypothyroidism presumably results from a relative or an absolute deficiency of thyroid secretion. Since iodine comprises about 65 per cent of thyroxin, it would appear that further investigation of the metabolism of iodine as evidenced by the iodine levels of the blood and urine is indicated. A characteristic alteration of the plasma cholesterol is found in patients with thyroid deficiency. This aspect has been investigated by several workers both before and after treatment with desiccated thyroid. The results of these investigations have shown that the level of the cholesterol in the blood is of value in the differential diagnosis of borderline cases of hypothyroidism. This study had as its purpose the following determinations:The level of the iodine in the blood
Archives of Internal Medicine167114-12810.1001/archinte.1941.00200010124008
Thyroid volumecardiovascular, myocardium4Fisher, C.E.; Mulligan, R. M.1943Quantitative study of correlation between basophilic degeneration of myocardium and atrophy of thyroid glandAmerican Heart Journal62684410.1016/S0002-8703(43)90302-3http://www.sciencedirect.com/science/article/pii/S0002870343903023
Atrophic ThyroiditisAdrenals, diabetes4Bennett, Leslie L.; Koneff, Alexei A.1946Atrophy of the thyroid and hypertrophy of the adrenal in rats with alloxan diabetes
In animals with alloxan-induced diabetes, thyroid atrophy and adrenal hypertrophy
The Anatomical Record19611-Jan10.1002/ar.1090960102http://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1002/ar.1090960102/abstract
AntibodiesTBAb, TSAb, Graves' disease, testing, assays, lab study4Valente, W A; Vitti, P; Yavin, Z; Yavin, E; Rotella, C M; Grollman, E F; Toccafondi, R S; Kohn, L D1982Monoclonal antibodies to the thyrotropin receptor: stimulating and blocking antibodies derived from the lymphocytes of patients with Graves disease.
Human monoclonal antibodies have been generated from heterohybridomas obtained by fusing mouse myeloma cells with peripheral lymphocytes from patients with active Graves disease. This report characterizes four antibodies as presumptive thyrotropin receptor antibodies because they specifically inhibit thyrotropin binding and competitively inhibit thyrotropin-induced cAMP levels in human thyroid cells. Two of these antibodies, 208F7 and 206H3, are representative of autoimmune stimulators in Graves disease sera because they stimulate thyroid function in all assays, including the mouse bioassay; their ability to inhibit thyrotropin-induced cAMP increases in thyroid cells competitively is complemented by more than additive agonism at low (10 pM) thyrotropin concentrations. These stimulating antibodies interact more potently with human thyroid ganglioside preparations than with bovine thyroid or brain gangliosides; in contrast, they are poor inhibitors of 125I-labeled thyrotropin binding to liposomes containing the glycoprotein component of the human thyrotropin receptor. Antibodies 129H8 and 122G3 appear to be representative of inhibiting or "blocking" antibodies in Graves disease sera. Thus they have no intrinsic stimulatory action in assays of thyroid function but rather inhibit thyrotropin activity in the assays tested. These two antibodies do not react with human thyroid gangliosides but are strong inhibitors of thyrotropin binding to liposomes containing the high-affinity glycoprotein component from human, bovine, and rat thyroid membranes. The data unequivocally establish the pluritopic nature of the immunoglobulins in Graves disease and relate individual components or determinants of the thyrotropin receptor structure with specific autoimmune immunoglobulins.
Proceedings of the National Academy of Sciences of the United States of America21796680-6684https://www.ncbi.nlm.nih.gov/pmc/articles/PMC347192/
Thyroid volumeKidney atrophy, cystinosis, case,4Koizumi, Fumitomo; Koeda, Takane; Wakaki, Kunihiko; Matumoto, Michio; Kobashi, Kyoichi; Akao, Teruaki; Fukase, Masayuki1985Cystinosis with Marked Atrophy of the Kidneys and Thyroid
The eldest autopsied case (a 23-year-old man) of infantile form of cystinosis with uremia and myxoedema was reported. The cystine content per gram wet tissue of various organs was arranged as follows: the thyroid (4.61 mg), kidney (1.71 mg), eye (0.75 mg), spleen (0.65 mg), liver (0.49 mg), and brain (0.016 mg). In polariased light microscopy, cystine crystals were detected in the epithelial cells and epithelial lumina of both kidneys by Wollaston test, and foam cells with cystine crystals were histologically found in the reticuloendothelial and other organs, especially in the bone marrows. Moreover, electron microscopic findings revealed square, rectangular or lozenge-shaped small cystine crystal profiles in osmophilic dense bodies of the histiocytic cells and in the cytoplasm of the foam cells. In some of them, positive reaction for acid phosphatase activity was specifically localized at the periphery of the cystine crystal profiles.
Pathology International135145-15510.1111/j.1440-1827.1985.tb02213.xhttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1111/j.1440-1827.1985.tb02213.x/abstract
Antibodiesreceptors4Bryant, William P.; Bergert, Elizabeth R.; Morris, John C.1995Identification of Thyroid Blocking Antibodies and Receptor Epitopes in Autoimmune Hypothyroidism by Affinity Purification Using Synthetic TSH Receptor Peptides
To examine the interaction of immunoglobulins from patients with newly diagnosed hypothyroidism with the TSH receptor (TSHr), we tested protein-A purified IgG in an ELISA assay with a series of peptides representing the entire extracellular domain (ECD) of human TSHr. Antibodies bound, on average, 4.1 peptides (range 0–16) per patient, and antibodies from 26 of 30 patients (86.6%) demonstrated binding to at least one peptide. Six of the 20-mer peptides (61, 151, 181, 301, 361, 376) were most frequently recognized. These were used to construct affinity columns and separate IgGs from 10 patients into bound and unbound fractions. All fractions were tested for their ability to stimulate and inhibit cAMP generation in FRTL-5 cells. Inhibitory IgGs were purified from 9 patients (90%), suggesting that the incidence of blocking antibodies (TBAb) in autoimmune hypothyroidism is higher than previously reported. 7 of 10 patients had antibodies that recognized peptide 361 further supporting the importance of this epitope in TBAb binding. Anti-microsomal and anti-thyroglobulin antibodies did not co-purify with inhibitory antibodies, and were always in the unbound fractions. We found no correlation between the pattern of antibody binding or bioactivity with clinical manifestations of hypothyroidism. Conclusions: (1) The majority of patients with autoimmune hypothyroidism have antibodies against the TSHr-ECD that recognized linear epitopes. Most have antibodies directed at more that one site and the pattern is quite heterogeneous. (2) Six sites (noted above) are most frequently recognized. (3) Inhibitory antibodies are distinct from anti-microsomal and anti-thyroglobulin antibodies.
AntibodiesTSH, cAMP, blocking4Dallas, J. S.; Cunningham, S. J.; Patibandla, S. A.; Seetharamaiah, G. S.; Morris, J. C.; Tahara, K.; Kohn, L. D.; Prabhakar, B. S.1996Thyrotropin (TSH) receptor antibodies (TSHrAb) can inhibit TSH-mediated cyclic adenosine 3',5'- monophosphate production in thyroid cells by either blocking TSH binding or affecting a step subsequent to TSH binding
In the present study, rabbit antibodies that possess thyroid stimulation-blocking activity were used to investigate potential mechanisms by which TSH receptor antibodies can inhibit thyroid cell function. The antibodies were produced against two synthetic peptides corresponding to amino acids 357-372 (p357) and 367-386 (p367) of the human TSHr (hTSHr). By enzyme-linked immunosorbent assay, both antisera (alpha 357 and alpha 367) had high titers ( &gt; 1:100,000) of IgG against their respective peptides and recombinant extracellular TSHr protein (ETSHr); alpha 357 had a low IgG titer to p367 (1:800), and alpha 367 had a low IgG titer to p357 ( &lt; 1:200). Based on competitive inhibition studies, alpha 357 and alpha 367 displayed similar relative binding affinities for their respective peptides and for recombinant ETSHr. When tested by commercial RRA, alpha 357 did not block (TSH binding inhibition index, -3.7%), whereas alpha 367 blocked TSH binding to TSHr (TSH binding inhibition index, 53.9%). The blocking effect of alpha 367 could be reversed by incubating the antiserum with p367 before assay. When applied alone to FRTL-5 cells, IgG from alpha 357 inhibited [compared to normal rabbit IgG (NRI); P &lt; 0.01] based cAMP production by the cells, whereas IgG from alpha 367 did not. IgG from both alpha 357 and alpha 367, however, were able to inhibit (P &lt; 0.001) TSH-mediated cAMP production by FRTL-5 cells [bovine (b) TSH, 2.5 x 10(-10) M; cAMP (mean +/- SD; picomoles per ml): NRI, 62.5 +/- 6.1; alpha 357, 12.2 +/- 2.4; alpha 367, 36.2 +/- 3.5]. Alpha 357 continued to inhibit (P &lt; 0.05) cAMP production by FRTL-5 cells in 10(-8) M bTSH, whereas alpha 367 no longer inhibited cAMP production at bTSH concentrations above 5 x 10(-10) M. Compared to NRI, both alpha 357 and alpha 367 were also able to inhibit (P &lt; 0.001) Graves' IgG-mediated cAMP production by FRTL-5 cells. When IgG were tested on FRTL-5 cells in the presence of 10(-7) M forskolin, only alpha 357 inhibited (P &lt; 0.001) cAMP production (NRI, 75.1 +/- 4.8; alpha 357, 52.3 +/- 4.5; alpha 367, 77.2 +/- 1.4). To determine whether the inhibitory effect of alpha 357 on forskolin-mediated stimulation was thyroid cell dependent, IgG were tested on Chinese hamster ovary (CHO) cells transfected with the complementary DNA of the hTSHr (CHO-R). Again, alpha 357 inhibited (P &lt; 0.005) cAMP production mediated by forskolin (at 10(-7) M; NRI, 68.7 +/- 4.4; alpha 357, 36.8 +/- 5.7; alpha 367, 64.6 +/- 8.5). alpha 357 did not inhibit forskolin-mediated cAMP production by untransfected CHO cells (CHO-N), indicating that the inhibitory effect of alpha 357 on forskolin stimulation was TSHr dependent. In addition, alpha 357 inhibited (P &lt; 0.01) basal cAMP production by CHO-R cells, but not by CHO-N cells. alpha 367 had no effect on the basal cAMP production in either CHO-R or CHO-N cells. Neither alpha 357 nor alpha 367 inhibited cholera toxin-mediated cAMP production in FRTL-5 cells. In all relevant bioassays, the inhibitory effects of alpha 357 and alpha 367 could be reversed by preincubating the IgG with the respective peptides. From these data, we conclude that 1) alpha 367 binds to the ETSHr and blocks TSH-mediated cAMP production by inhibiting TSH from binding to its receptor; 2) alpha 357 binds to the TSHr and, without blocking TSH binding, inhibits TSH-mediated cAMP production at a step(s) subsequent to ligand binding that affects adenylate cyclase activity; and 3) forskolin-mediated cAMP production by thyroid cells can be inhibited by IgG that bind directly to the TSHr.
Atrophic ThyroiditisTGAb, TPOAb, TBAb, radiation therapy, cancer, chemotherapy4Kikawa, Y.; Takeuchi, M.; Sudo, M.; Iida, Y.; Kasagi, K.; Konishi, J.1996Development of primary hypothyroidism with antithyroglobulin, antiperoxidase, and blocking-type thyrotropin receptor antibodies after radiation therapy for neuroblastoma
We describe a girl with hypothyroidism and blocking-type thyrotropin receptor antibodies that developed after chemotherapy and irradiation of the neck region for neuroblastoma. Results of thyroid studies before treatment were normal. Twenty months after completion of treatment, the girl had hypothyroidism with high titers of blocking-type thyrotropin receptor antibodies, antithyroglobulin, and antiperoxidase antibodies.
The Journal of pediatrics6129909-12
Thyroid volumeBreast cancer, TPOAb, cancer outcome4Smyth, P. P. A.1998Serum Thyroid Peroxidase Autoantibodies, Thyroid Volume, and Outcome in Breast Carcinoma
The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.
Journal of Clinical Endocrinology & Metabolism8832711-271610.1210/jc.83.8.2711
Antibodiestesting, assays, TSAb, TBAb, cAMP, lab study with human sera4Wallaschofski, H.; Paschke, R.1999Detection of thyroid stimulating (TSAB)- and thyrotropin stimulation blocking (TSBAB) antibodies with CHO cell lines expressing different TSH-receptor numbers
BACKGROUND With the aim of assaying TSH-receptor antibodies (TSHR AB) and to distinguish different TSHR AB activities, several in vitro bioassays for the determination of TSHR AB have been developed. The bioassay using the CHO cell line expressing the hTSH-receptor (hTSHR) is the most sensitive and least cumbersome assay system. However, up to now, the CHO cell bioassay has been performed with cells expressing much higher TSHR numbers than normal thyroid epithelial cells and with variable assay conditions. DESIGN AND PATIENTS To determine the optimal CHO cell bioassay conditions we therefore systematically investigated the influence of different assay parameters on the sensitivity of the CHO cell bioassay for the detection of TSHR antibodies in 197 patients with Graves' disease treated with antithyroid drugs and tried to define optimal assay conditions. RESULTS Compared to JP09 cells (90 000 hTSHR/cell), JP26 cells (2000 hTSHR/cell) exhibited a higher stimulation index (maximal bTSH-stimulated cAMP production/cAMP production stimulated by pooled normal serum without bTSH) which is most likely due to the lower number of hTSHR expressed per JP26 cell compared to JP09 cells. Due to their low nonspecific stimulation by normal sera, 40 000 JP26 cells per well of a 96 well plate was found to be the optimal cell number. Moreover, a serum dilution of 1/10 yielded the highest stimulation results of bTSH and thyroid stimulating antibodies (TSAB). Applying these optimal conditions for the determination of TSH-receptor antibodies only 10 of 34 TSBAB positive serum samples detected with JP26 cells were detectable with the JP09 cell line. In 197 patients with Graves' disease treated with antithyroid drugs 111 (56%) were TSAB positive. 34 (40%) of 86 TSAB negative patients were positive for thyrotropin stimulation blocking antibodies (TSBAB). CONCLUSION Improvement of CHO bioassay conditions for the determination of TSH receptor antibodies leads to increased bioassay sensitivity which is most pronounced for the detection of TSBAB. Whether this increased sensitivity for the determination of TSBAB is of prognostic significance for detecting possible sequential changes in the individual TSHR AB profile of patients with Graves' disease, remains to be determined by further follow up studies.
Clinical Endocrinology350365-37210.1046/j.1365-2265.1999.00672.xhttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1046/j.1365-2265.1999.00672.x/abstract
Atrophic ThyroiditisT4 therapy, dosage, Hashimoto's, Graves', Thyroid cancer,4Gordon, M. B., & Gordon, M. S.1999Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism.
OBJECTIVE: To compare the levothyroxine replacement dose in 181 patients with various causes of hypothyroidism.
METHODS: We analyzed the dose of levothyroxine used in the following five patient groups: (1) 37 patients with hypothyroidism after radioiodine therapy for Graves' thyrotoxicosis who were receiving a stable (for at least 4 years) replacement dose (mean time after 131 I therapy, 11.3 years); (2) 36 patients with Hashimoto's hypothyroidism (chronic autoimmune thyroiditis with a goiter or positive test results for antithyroid antibodies); (3) 36 patients with central hypothyroidism; (4) 36 patients with hypothyroidism after near-total thyroidectomy and 131 I therapy for thyroid carcinoma with negative total-body 131 I scans who were euthyroid when receiving levothyroxine; and (5) 36 patients with atrophic thyroiditis (no goiter and negative test results for antithyroid antibodies). Adequacy of levothyroxine replacement dose was defined as a normal thyrotropin level and clinical euthyroidism in patients with primary hypothyroidism and a serum free thyroxine index in the upper half of the normal range in conjunction with clinical euthyroidism in patients with central hypothyroidism.
RESULTS: The mean (+/- standard error of the mean) replacement dosage of levothyroxine (mg/kg per day) in patients with atrophic thyroiditis (1.26 +/- 0.07) was lower (P<0.05) than in patients with Hashimoto's hypothyroidism (1.59 +/- 0.07) and those with hypothyroidism after radioiodine therapy (1.56 +/- 0.05). These doses, in turn, were lower (P<0.01) than those in patients with central hypothyroidism (1.88 +/- 0.10) or euthyroid thyroid carcinoma (2.08 +/- 0.07). In a separate analysis, the levothyroxine dose in 43 patients with hypothyroidism after 131 I treatment was evaluated serially over time. The mean levothyroxine dosage increased from 0.87 +/- 0.12 at 6 months after 131 I therapy to 1.57 +/- 0.09 at 7 years (P<0.001). The serum thyrotropin concentration (in mU/mL) during levothyroxine therapy in patients with central hypothyroidism (0.31 +/- 0.08) was lower (P<0.01) than in patients with hypothyroidism after 131 I therapy (1.69 +/- 0.37), Hashimoto's hypothyroidism (1.39 +/- 0.20), atrophic thyroiditis (1.86 +/- 0.22), and euthyroid thyroid carcinoma (1.48 +/- 0.26).
CONCLUSION: The levothyroxine replacement dose varies with the cause of the hypothyroidism.
Endocrine Practice55233–238.https://doi.org/10.4158/EP.5.5.233
Thyroid volumeStats, France, sex, weight, height, TSH, iodine,4Barrère, X.; Valeix, P.; Preziosi, P.; Bensimon, M.2000Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort
OBJECTIVE To study the relative importance of determinants of thyroid volume. DESIGN Cross-sectional study on a sample of subjects issued from the SU.VI.MAX cohort. SUBJECTS 2987 French subjects (1713 women aged 35-60 years and 1274 men aged 45-60 years). None of them had previous or present thyroid disease. MEASUREMENTS Thyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples. RESULTS For both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non-smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non-smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0.0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35-45 years) had a smaller thyroid volume than non-users (P = 0.0009). CONCLUSIONS The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long-lasting thyroid enlargement.
Clinical endocrinology352273
Antibodiestesting, assays, TBAb, TSAb, lab study,4Jordan, N. J.; Rinderle, C.; Ashfield, J.; Morgenthaler, N. G.; Lazarus, J.; Ludgate, M.; Evans, C.2001A luminescent bioassay for thyroid blocking antibodies
Thyroid blocking antibodies (TBAb) have a role in the development of hypothyroidism and in the neonate are responsible for transient hypothyroidism. Specific measurement of TBAb requires a bioassay, but current methods are lengthy and cumbersome.
We describe a rapid luciferase‐based method for the detection of TBAb using the * cell line which is suitable for the provision of a clinical service Chinese hamster ovary (CHO) cells were transfected with human TSH‐R together with G418 resistance and a cAMP responsive luciferase construct. Stable pools of transfected cells were selected and clones identified by limiting dilution. Clone * gave the best response to stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent bioassay conditions have been optimized and validated using 12 serum samples from patients found to be TBAb positive in a bioassay using an established method quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating antibodies (TSAb) on the calculation of Inhibition Index (InI) using two previously described formulae have been investigated and we have used serum containing both TSAb and TBAb to investigate detection of TBAb in samples containing more than one type of activity. * displays a dose dependent increase in luciferase expression in response to stimulation with bovine (b) TSH which is more effective in serum free medium than in salt free buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either serum or an immunoglobulin preparation. Using optimized assay conditions, challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31 euthyroid sera to determine a reference range: InI values >23% were considered positive. Twelve samples previously shown to contain TBAb by an established method quantifying cAMP by RIA were positive by the luciferase‐based assay. Of control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis, 12/12 multinodular goitre were negative. We demonstrated that if more complex formulae are used to calculate InI, false positive TBAb results can be obtained in samples containing only TSAb.
Finally, when sera contain both TSAb and TBAb, the net activity of stimulating and blocking antibodies is detected in the bioassay. Where TSAb are also present, analysis of serum may be required at several dilutions to detect TBAb. We describe the production of a new cell line, * and its use to develop a luminescent bioassay for TBAb suitable for clinical use.
Comparing two established methods of calculating TBAb, we found that they do not give identical results. In light of this, the high prevalence reported for TBAb in some studies has to be considered with caution.
Clinical Endocrinology354355–36410.1046/j.1365-2265.2001.01193.x
Thyroid volumeAnorexia nervosa, Low T3 syndrome, TRH-TSH test, lean body mass, age,4Klinkby Støving, René; Bennedbæk, Finn Noe; Hegedüs, Laszlo; Hagen, Claus2001Evidence of diffuse atrophy of the thyroid gland in patients with anorexia nervosa
Objective The altered function of the hypothalamic-pituitary-thyroid axis (HPT) in anorexia nervosa (AN) patients has not been clearly elucidated so far. Low triiodothyronine (T3) syndrome and a blunted and delayed thyrotropin (TSH) response to exogenously administrated thyrotropin-releasing hormone (TRH) are common findings. However, no attention has been paid to thyroid morphology in AN patients. Method We performed an ultrasonographic (US) evaluation of the thyroid gland in 22 AN patients and in 44 age and sex-matched control subjects. Lean body mass (LBM) was determined by dual-energy X-ray absorptiometry. Results US-determined thyroid volume was significantly reduced in AN patients (9.2 ± 0.4 vs. 17.8 ± 1.2 ml in the controls; M ± SEM; p < 10−4). In healthy subjects, it has previously been established that thyroid volume can be estimated from age and body weight. In the present study, the measured thyroid volume in patients with AN was significantly lower than the predicted thyroid volume (measured: 9.2 ± 0.4 vs. estimated: 12.2 ± 0.2 ml; p < 10−4). Furthermore, in the AN patients, the thyroid size was not correlated to body mass index (BMI) or LBM. Discussion Thyroid volume in AN patients was markedly reduced compared with the control group and with the volume expected from age and body weight or LBM. This indicates thyroid atrophy, which, hypothetically, could be involved in a vicious circle maintaining anorectic or depressive symptomatology. © 2001 by John Wiley & Sons, Inc. Int J Disord 29: 230–235, 2001.
International Journal of Eating Disorders229230-23510.1002/1098-108X(200103)29:2<230::AID-EAT1013>3.0.CO;2-Phttp://onlinelibrary.wiley.com.ezproxy.lib.ucalgary.ca/doi/10.1002/1098-108X(200103)29:2<230::AID-EAT1013>3.0.CO;2-P/abstract