HYPOTHYROIDISM AND HYPERTHYROIDISM

PRESENTED BY 2017/2018 SET(SENIOR POSTING)

MODERATED BY DR IHEKAIKE/ DR NEPYIL

PRESENTERS

• ARUMONA SAMUEL BHU/18/01/01/0085
• ARUMS CHRISTIANA JOSHUA BHU/17/01/01/0224
• AYOOLA ABIMBOLA BHU/17/01/01/0157
• BABARINDE IBUKUNOLUWA BHU/17/01/01/0046
• BAIYEE ZAINAB BHU/17/01/01/0134
• BALASA PATIENCE BHU/17/01/01/0281
• BARNABAS RUTH BHU/19/01/01/0045
• BENBELLA BENEDICTA BHU/17/01/01/0067
• ADAMANI BETHANY

OUTLINE

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• Introduction
• Epidemiology
• Etiology
• Pathogenesis
• Clinical Features
• Management
• Treatment
• Conclusion
• References

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THE THYROID GLAND

The thyroid gland is a small, butterfly shaped, gland, located at the base of the neck, in front of the trachea.

The thyroid gland secretes 3 hormones namely;

• Thyroxine (T4)
• Triiodothyronine (T3)
• Calcitonin

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THE THYROID GLAND

Physiologic Effects of Thyroid Hormones �

• Growth: Normal somatic growth
• Development: Brain maturation, development and function
• Metabolism: Increase the BMR (basal metabolic rate)

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Metabolic Effects of Thyroid Hormones

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• Carbohydrate metabolism: Increased glycogenolysis, gluconeogenesis and entry of glucose into cells

• Lipid metabolism: fat mobilization and oxidation of fatty acids
• Protein metabolism: increased catabolism

Effects of Thyroid Hormones on Body Systems�

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• CVS: increases heart rate and cardiac output
• CNS: promotes mental activity
• GIT: increases motility

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HYPOTHYROIDISM

INTRODUCTION

• Hypothyroidism is a condition where there is decreased thyroid hormone level in the blood, which may be due to primary, secondary or tertiary causes.
• In primary hypothyroidism, the lesion is in the thyroid gland resulting in decreased production of T3 and T4 and increased TSH levels.

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• In secondary or central hypothyroidism, there is a defect in the pituitary gland or the thyrotrophic cells (Thyroid stimulating hormone deficiency)
• In tertiary hypothyroidism, there is a defect in the hypothalamus and its secretion of thyrotropin releasing hormone (TRH)
• Hypothyroidism may be congenital or acquired

EPIDEMIOLOGY

• World wide prevalence of hypothyroidism is 1:4000
• Congenital hypothyroidism is the commonest endocrine disease of infancy with varying incidence in different ethnic group
• Incidence of primary congenital hypothyroidism is approximately 1 in 3500-5000 live birth. The incidence is lower in black Americans(1/32,000) but higher in native Americans
• Commonly associated with down syndrome

EPIDEMIOLOGY

• Acquired hypothyroidism occur in approximately 1:1250 of school age children symptoms appear after first year of life or in adolescence
• Twice more common in females than males
• Occurs after the age of 1year

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AETIOLOGY

• CONGENITAL HYPOTHYROIDISM

Approximately 75% of infants with congenital hypothyroidism have defects in thyroid gland development, 10% have hereditary defects in thyroid hormone synthesis or uptake, 5% have secondary (pituitary) or tertiary (hypothalamus)

hypothyroidism, and 10% have transient hypothyroidism.

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The causes of congenital hypothyroidism includes;

1. Thyroid Dysgenesis
2. Familial Thyroid Dyshormonogenesis
3. Transplacental passage of maternal TSH-binding inhibitory antibodies
4. Maternal Exposure to Radioiodine
5. Thyrotropin deficiency or unresponsiveness due to hypothalamus or pituitary defects
6. Iodine deficiency endemic goiter

• Thyroid Dysgenesis: Is a cause of congenital hypothyroidism where the thyroid gland is missing (aplasia), severely underdeveloped (hypoplasia) or ectopic. It accounts for 85% of cases of congenital hypothyroidism.
• Thyroid dysgenesis occurs sporadically in most cases but is occasionally familial because of mutations or deletions of genes (TSHR, PAX8, NKX2-1, FOXE1, and NKX2-5) that are involved in fetal thyroid formation.

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Familial Thyroid Dyshormonogenesis: These are autosomal recessive inborn errors of thyroid hormone synthesis, secretion, or uptake.

The following 8 inborn errors have been identified:

Failure to respond to TSH secondary to defective activation of the thyroid receptor and related cyclic adenosine monophosphate (cAMP) signal transduction pathway

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• Defect in trapping of iodide secondary to sodium-iodide symporter failure
• Defective oxidation of iodide to iodine secondary to thyroid peroxidase deficiency
• Defective coupling of iodotyrosines
• Deiodination defects
• Defective thyroglobulin synthesis
• Defective proteolysis of thyroglobulin
• Release of T3 and T4 into the circulation.

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Transplacental passage of maternal TSH-binding inhibitory antibodies: This can cause transient neonatal hypothyroidism.

In mothers with autoimmune thyroiditis, immunoglobulin G (IgG) antithyroid antibodies can be transmitted across the placenta.

These antibodies block binding of TSH to its receptor on the fetal thyroid, preventing the release of thyroid hormone.

The half-life of these antibodies is approximately 1 week, and this form of congenital hypothyroidism usually resolves within 2-3 months of life.

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Maternal exposure to radioiodide, goitrogenic drugs, iodide or antithyroid drugs: The fetal thyroid is able to trap iodide by 70-75 days' gestation.

Hypothyroidism can develop if the mother is exposed to radioiodine to treat graves disease or thyroid carcinoma.

Iodide can be found in the following; Amiodarone, neonatal exposure to iodine-containing antiseptics, Propylthiouracil, or methimazole.

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• Iodine deficiency endemic goitre: Congenital iodine deficiency syndrome(cretinism) is a medical condition present at birth marked by impaired physical and mental development, due to insufficient dietary iodine during pregnancy.

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AETIOLOGY CON’TD

• ACQUIRED HYPOTHYROIDISM
• Is caused by the following;
• Autoimmune Thyroiditis (Hashimoto’s disease)
• Iodine Deficiency
• Drug-induced
• Radiation Therapy
• Thyroidectomy (total or subtotal)

Autoimmune Thyroiditis (Hashimoto thyroiditis): This is the commonest cause of acquired hypothyroidism, it occurs when the immune system attacks the thyroid gland, causing inflammation ad hyperthyroidism initially, followed by hypothyroidism.

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• It appears to require both an environmental trigger and a genetically determined defect.
• Evidence suggests that the disease develops secondary to a defect in cell-mediated immunity whereby suppressor T lymphocytes fail to destroy forbidden clones of thyroid-directed T lymphocytes, which form as a part of random immunologic differentiation.

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An increased frequency occurs in children with

-trisomy 21 syndrome

-Ulrich-Turner syndrome 

-Klinefelter syndrome

-or other autoimmune diseases, including type 1 diabetes mellitus.

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• Iodine deficiency: It usually occurs in children whose diet is restricted because of multiple food allergies or in those who require long-term parenteral nutrition.

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Drug-induced hypothyroidism: Drug-induced hypothyroidism can result from use of thioamides, lithium, Amiodarone use in the adolescent , and excess dietary iodine consumption by the mother up to 12mg in the form of nutritional supplements. In the neonate topical iodine containing antiseptic used in the nurseries and by surgeons can also cause transient congenital hypothyroidism.

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Exposure to these substances most often results in biochemical evidence of hypothyroidism in the absence of clinical symptoms (transient congenital hypothyroidism). This is called the wolff-chiakoff effect , but normally after a few days the thyroid hormone return to normal, “escape phenomenon”

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Radiation therapy: Less Commonly, hypothyroidism may occur after radiation therapy to the head and neck for certain cancers, after total body irradiation in preparation for bone marrow transplant

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• Thyroidectomy: Surgical removal of the thyroid gland totally would definitely lead to hypothyroidism. And up to 30-50% of patients that had half of their thyroid removed would develop hypothyroidism.

CLINICAL FEATURES

CONGENITAL HYPOTHYROIDISM

1. Asymptomatic at birth: Transplacental passage of moderate amount of T4.Birth weight and length are normal but the head size may be slightly increased.

2. Prolonged neonatal jaundice: caused by delayed maturation of glucuronide conjugation. may be the earliest presentation.

3. Non specific signs and symptoms such as feeding problem, lethargy, constipation, poor muscle tone.

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CLASSICAL SIGNS BY (6-12WEEKS AFTER BIRTH)

• Coarse facies
• Large protruding tongue
• Large open fontanels
• Hoarse cry
• Coarse dry and molted skin
• Umbilical hernia
• Hypothermia
• Myxoedema
• Hirsute forehead
• Refractory anaemia

Delayed physical and mental development

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By 3-6 months of age the clinical picture is fully developed.

This is because the symptoms appear gradually the diagnosis is often delayed except with neonatal screening programs

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CLINICAL FEATURES�ACQUIRED HYPOTHYROIDISM

1. Growth and Developmental Delay: One of the most prominent signs of hypothyroidism in children is growth and developmental delay. Infants may have poor weight gain and slower growth compared to their peers. They may also have delayed milestones such as sitting, crawling, or walking. In older children, there may be a decline in growth velocity, resulting in short stature. 

2. Fatigue and Lethargy: Children with hypothyroidism often experience fatigue and lethargy. They may appear tired even after getting adequate sleep and may lack energy for physical activities. This can lead to decreased participation in school or extracurricular activities.

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3. Cold Intolerance: Hypothyroidism can affect the body's ability to regulate temperature, leading to increased sensitivity to cold temperatures. Children with hypothyroidism may complain of feeling cold even in warm environments and may require additional layers of clothing to stay warm.

4. Constipation: Another common symptom of hypothyroidism in children is constipation. The decreased production of thyroid hormones can slow down the digestive system, resulting in infrequent bowel movements and difficulty passing stool.

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5. Dry Skin and Hair: Hypothyroidism can cause dryness of the skin and hair due to reduced oil production. Children may have rough, scaly skin that is prone to itching and dry, brittle hair that is difficult to manage.

6. Hoarse Voice: The vocal cords can be affected by hypothyroidism, leading to a hoarse or husky voice in children. This can be particularly noticeable during periods of increased vocalization, such as when singing or speaking loudly.

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7. Delayed Puberty: In older children and adolescents, hypothyroidism can delay the onset of puberty. This can manifest as delayed breast development in girls or delayed testicular enlargement in boys.

8. Mental Health Issues: Hypothyroidism can also impact a child's mental health. Children may experience symptoms of depression, such as low mood, irritability, and difficulty concentrating. They may also have impaired memory and cognitive function.

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• 9. Puffy Face and Protruding Tongue: In some cases, children with hypothyroidism may have a puffy face and a protruding tongue. This is due to the accumulation of fluid and increased deposition of glycosaminoglycans in the tissues.
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• 10. Delayed Tooth Eruption: Hypothyroidism can affect tooth development and eruption in children. They may have delayed eruption of primary (baby) teeth or permanent teeth, leading to dental abnormalities.

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• It is important to note that not all children with hypothyroidism will exhibit all of these clinical features. The severity and combination of symptoms can vary from child to child.

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MANAGEMENT

For Congenital Hypothyroidism:

History:

History of dry skin, feeding problem, constipation, poor activity.

Examination:

large tongue, open posterior fontanelle, umbilical hernia, skin mottling

Diagnosis:

• Screening : neonatal hypothyroid index(>3)
• Relies on the use of sensitive serum TSH and T4 assays : low T4,raised TSH(usually done after 72hrs of life)
• T3 may be normal and are not helpful in the diagnosis.
• X-ray of the skeletal structures may show retardation of osseous development
• Low serum thyroglobulin
• Radionuclide studies to evaluate iodine
• USS

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TREATMENT

• Replacement therapy with Sodium L-thyroxine orally for life, started early within 3weeks of life for optimal effect on brain maturity and growth.
• Starting dose 10-15microg/kg/day,tapered to 4microg/kg/day between 1-10yrs,then to 2microg/kg/day in adult.
• Prognosis: early diagnosis and adequate treatment for the first week of life result in normal linear growth and intelligence. Delay in treatment beyond 3 months or inadequate treatment and poor compliance in the first 2-3yrs of life result in variable degrees of brain damage.

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• For Acquired hypothyroidism:
• History:
• Usually insidious in onset so difficult to diagnose.
• Present in 1^st year of life or adolescent.
• Decreased appetite, lethargy, constipation, cold intolerance, decreased energy and increased need for sleep.
• Headaches and visual disturbance may occur with long standing hypothyroidism.

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On examination: coarse hair, cold dry skin, galactorrhoea, delayed puberty, breast development in girls and macro-orchidism in boys (pseudo-precocious puberty)

• Diagnosis: Relies on the use of sensitive serum TSH and T4 assays : low T4,raised TSH(usually done after 72hrs of life)
• T3 may be normal and are not helpful in the diagnosis.
• Low serum thyroglobulin
• Radionuclide studies to evaluate iodine
• USS

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• Delayed skeletal maturation on X-ray.
• Fine needle aspiration biopsy if there’s nodules on palpation or USS.
• In children older than 2yrs,the serum cholesterol is usually elevated.
• Lymphocytic infiltrates in Hashimoto’s disease.

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• Synthetic L-thyroxine,3-5microg/kg as a single daily oral dose for life.
• Prognosis: all these changes return to normal with adequate replacement of T4,but in children with long standing hypothyroidism, catch up growth may be incomplete.

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HYPERTHYROIDISM

HYPERTHYROIDISM

INTRODUCTION�

• Hyperthyroidism refers to over activity of the thyroid gland which leads to a sustained increase in synthesis and release of thyroid hormones and consequently accelerated metabolism in the peripheral tissues. During childhood, it is caused by Graves disease (an autoimmune disorder) with few exceptions Hyperthyroidism is the most prevalent cause of thyrotoxicosis but it is a relatively rare condition in children .

• Neonatal Hyperthyroidism usually begins prenatally and is present at birth but diagnosis may be delayed, it is caused by Transplacental passage of high titers of thyroid stimulating antibodies from the mother, The mothers of these infants have Graves disease.

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EPIDEMIOLOGY

• Hyperthyroidism is relatively uncommon in childhood and adolescence ,0.94 per 100,000 under 15years have thyrotoxicosis and 84% of them is due to Graves disease.
• Graves disease occurs approximately in 0.02% of children i.e 1:5000
• It has a peak incidence in the 11-15 year old age group

• Female: male ratio is 5:1
• Most children with Graves disease have a positive family history of some form of autoimmune thyroid disease
• Neonatal hyperthyroidism occurs only in 2% of infants born to mothers with active Graves disease

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AETIOLOGY

• In children, hyperthyroidism is almost always due to:
• Grave’s disease - autoimmune over production of T3 and T4

Other causes include:

• Toxic solitary or multinodular goiter (Plummer disease)
• Subacute thyroiditis (viral)

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• Acute suppurative thyroiditis
• McCune-Albright syndrome (rare)
• Chronic lymphocytic thyroiditis
• Hyper functioning thyroid carcinoma
• Thyrotoxicosis factitia
• TSH-secreting pituitary tumours (have only been reported in adults)

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Grave’s disease(Thyrotoxicosis):�

• This results from a autoimmune phenomenon in which antibodies directed at the TSH receptor (TRAb) on the surface of the thyroid follicular cells bind and stimulates the production of thyroid hormone (thyrotropin receptor stimulating antibodies)
• In children and adolescents, it is the cause of hyperthyroidism >90% of cases. There is an increased incidence of Graves.

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• disease during puberty, with 80% of cases occurring after 11 years of age. The primary mechanism is stimulating antibodies for the TSH receptor, and the balance between stimulating and blocking determines the severity of the disease. Many children with Graves disease have a family history of autoimmune thyroid disease or other autoimmune conditions.
• Children with trisomy 21 are at increased risk of the disease

Neonatal Graves disease (Congenital Hyperthyroidism)

• In infants, hyperthyroidism is rare but potentially life-threatening. It develops in fetuses of women with current or prior Graves disease.
• Here, maternal autoantibodies against the thyroid receptor for thyroid-stimulating hormone (TSH) over stimulate thyroid hormone production by binding to TSH receptors in the thyroid gland.

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• These antibodies cross the placenta and cause thyroid hyper function in the fetus (intrauterine Graves disease), which can result in foetal death or preterm birth due to foetal hyperactivity or tachycardia.
• Infants ability to clear the antibodies after birth, makes neonatal Graves disease usually transient. However, variation in the clearance rate results in variation in duration of neonatal Graves disease.

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McCUNE-ALBRIGHT SYNDROME

• McCune-Albright syndrome (MAS) is a rare condition that results from post zygotic activating somatic mutations in the alpha subunit of the GNAS gene, leading to continued stimulation of endocrine glands

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• Constitutively active mutant GNAS results in increased cyclic adenosine monophosphate, which Promotes proliferation and autonomous function of endocrine organs throid gland in this case

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• Nearly 50% of people diagnosed with McCune-Albright syndrome have an enlarged thyroid gland. When the thyroid gland enlarges, it produces too much of the thyroid hormone (hyperthyroidism) that causes a fast heart rate, excessive sweating, high blood pressure and weight loss.

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PLUMMER DISEASE(Toxic multinodular goiter)

• Plummer disease, also known as toxic multi-nodular goiter (MNG), is a hormonally active multi-nodular goiter with hyperthyroidism. Plummer disease was first described by Henry Plummer, an American physician, in 1913.
• It's characterized by marked enlargement of the thyroid gland (goiter), firm thyroid nodules, and overproduction of thyroid hormone (hyperthyroidism).it's rare in children

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• HYPER FUCTIONING THYROID CANCER

These nodules produce extra thyroid hormone, which may lead to the development of hyperthyroidism.

• THYROTOXICOSIS FACTITA: also called alimentary thyrotoxicosis, exogenous thyrotoxicosis; its a condition of thyrotoxicosis caused by the ingestion of exogenous thyroid hormone.

• It can be the result of mistaken ingestion of excess drugs, such as levothyroxine [6] and Triiodothyronine, or as a psychiatric disorder where patients surreptitiously ingest thyroid hormone in excessive amounts. When confronted with the situation, they usually deny doing so.
• SUBACUTE THYRODITIS: is an acute inflammatory disease of the thyroid probably caused by a virus. Symptoms include fever and thyroid tenderness. Initial hyperthyroidism is common, sometimes followed by a transient period of hypothyroidism.

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• ACUTE SUPPURATIVE THYROIDITIS
• Patients with sub acute thyroiditis may briefly have hyperthyroidism but usually regain normal thyroid function
• Hyperthyroidism due to excess TSH secretion is rare, and mostly due to pituitary unresponsiveness to thyroid hormone.

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CHRONIC LYMPHOCYTIC THYROIDITIS

• Also called Hashimoto thyroiditis is an autoimmune disorder (like Graves disease).
• It is the most common cause of thyroid disease in childhood and adolescence.
• Seven times more frequent in girls than in boys. It may occur during the first 3 years of life but becomes sharply more common after 6 years of age and reaches a peak incidence during adolescence.
• In patients with CLT, antithyroglobulin and antithyroid peroxidase antibodies predominate.
• If present, TSI titers are low

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• The hyperthyroid phase of chronic lymphocytic thyroiditis (hashitoxicosis) is self-limited and responds to antithyroid therapy.

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• Antithyroid T lymphocytes and antibodies cause destruction of thyroid follicular cells, and hypothyroidism occurs over time.

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PATHOPHYSIOLOGY

• It is an autoimmune process
• There is a trigger in the production of antibodies
• These antibodies have structural similarities to the thyroid stimulating hormone
• Antibodies bind to the thyroid stimulating hormone receptor
• Once receptor is activated there is excess production of T3 and T4 hormones
• This in turn causes the clinical symptoms of hyperthyroidism and visible enlargement of the thyroid gland

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CLINICAL FEATURES

• In neonates and infants
• Intrauterine growth restriction and low birth weight
• Irritability, restlessness, hyperactivity
• Poor weight gain
• Increased appetite, vomiting, diarrhea
• Hyperthermia
• Failure to thrive
• Craniosynostosis, microcephaly
• Tachycardia, Tachypnea, hypertension
• Exophthalmos

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• Older children
• Hyperactivity, mood swings, marked decrease in concentration and school performance
• Heat intolerance, diaphoresis
• Fatigue, palpitations
• Increased appetite, weight loss, diarrhea
• Tremors
• Tachycardia, tachypnea, hypertension
• Exophthalmos
• Goiter

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MANAGEMENT

HISTORY

• Females more affected
• Insidious onset
• Early symptoms: irritability, restless, emotional ability (excessive crying), deteriorating school performance from short attention span

• Classical symptoms: increased appetite, weight loss, excessive sweating, heat intolerance, difficulty in sleeping at night, tiredness, easy fatigability
• Family history of autoimmune thyroid disease

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• EXAMINATION
• Hyperactive precordium, Dyspnea, tachycardia, cardiac enlargement, systolic hypertension, widened pulse pressure
• Frontal bossing with triangular facies and Craniosynostosis, microcephaly

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EXAMINATION CONT’D�

• Tremor
• Goiter (enlarged thyroid gland) is found in all cases
• Exophthalmos is usually mild in all patients
• Classic opthalmopathy of graves disease; which include lagging of the eyelids, upper eyelid retraction, infrequent blinking and stare is less frequent in pediatric group

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DIAGNOSIS

Diagnosis can be made from clinical features

• Elevated serum levels of T3 and T4, suppressed level of TSH
• Thyroid antibodies- ELISA- anti-TPO, TSI
• ECG: demonstrate cardiac manifestation

• Thyroid Ultrasound
• Lipid profile
• Fasting blood sugar

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TREATMENT

• Anti- thyroid medication: Carbimazole (Methimazole), Propylthiouracil
• Radioactive iodine 131I : is effective in children above 10 years and does not require pretreatment with antithyroid drug
• Beta blockers
• Calcium
• Vitamin D

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TREATMENT

• Surgery: subtotal thyroidectomy is done when patient is euthyroid with antithyroid drugs given over 2-3 months

Other Indication of surgery: malignancy, toxic multinodular goiter, failure of medical treatment, hypersensitivity to drugs, large goiter with compression symptoms

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Thyroid crisis/ Thyroid Storm

• This is a form of hyperthyroidism manifested by a severe biochemical derangement . It is usually of acute onset.
• Features include;
• Hyperthermia
• Tachycardia
• Heart failure
• Restlessness

There may be rapid progression to delirium, coma and death

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• Precipitants;
• Surgery
• Trauma
• Infection
• Radioactive iodine treatment.

CONCLUSION

Hypothyroidism and hyperthyroidism are potentially fatal conditions that can affect children, and can cause a wide range of symptoms, they however can be diagnosed and managed adequately.

REFERENCES

• Azubuike and Nkanginieme,(2016). Paediatrics and child health in Tropical region, 3rd edition, Part 16, Chapter 94, Page 952- 957.
• Nwokolo C, Ekpechi O.L. Nwokolo U. New foci of endemic goiter in Eastern Nigeria Trans. Roy. Sec. Trop. Med. Hgy 1965; 59: 342.
• [Guideline] Kahaly GJ, Bartalena L, Hegedüs L. The American Thyroid Association/American Association of Clinical Endocrinologists guidelines for hyperthyroidism and other causes of thyrotoxicosis: a European perspective. Thyroid. 2011 Jun. 21(6):585-91. [QxMD MEDLINE Link].

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REFERENCES

• https://www.msdmanuals.com/professional/pediatrics/endocrine-disorders-in-children/hyperthyroidism-in-infants-and-children

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• Oyenusi EE, Ajayi EO, Akeredolu FD, Oduwole AO. Pattern of Thyroid Disorders in Children and Adolescents Seen at the Lagos University Teaching Hospital, Nigeria, Over a 10-year Period. Niger Med J. 2017 May-Jun;58(3):101-106. doi: 10.4103/nmj.NMJ_156_16. PMID: 29962651; PMCID: PMC6009143.

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REFERENCES

• https://www.researchgate.net/publication/285720544_Clinical_characteristics_of_children_and_adolescents_with_thyroid_disorders_seen_at_the_University_of_Port_Harcourt_Teaching_Hospital_A_five_year_review
• https://reference .Medscape.com/article/922777-overview#a1

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