Liver & Thyroid
د.ريم قطان
اختصاصية بأمراض الهضم
اختصاصية بأمراض الغدد الصم والاستقلاب والتغذية
14-15-16/9/2022
المؤتمر العلمي الثالث والثلاثين
داماروز- دمشق
OUT LINES
hypothyroidism NAFLD
hyperthyroidism Clinical features shared with hepatic failure:
thyroid ca RAIU hyperammonia
thyroid treatments ATDS ascites
حالة سريرية
خزعة الكبد؟؟؟
The liver is usually considered to be a hormone-independent organ,
but a complex relationship indeed exists between thyroid gland and liver,
both in health and disease.
The role of liver
synthesizes the major thyroid hormone-transport proteins: thyroxine-binding globulin (TBG), transthyretin (TTR), and Albumin.
thyroid hormone transport and metabolism
thyroid hormone activation and inactivation through deiodinase activity
major variation in the bioavailability of thyroid hormones.
Liver dysfunction
The role of thyroid
the Oddi’s sphincter expresses thyroid hormone receptors, and thyroxine has a direct prorelaxing effect on the sphincter
bilirubin production and composition
hepatic metabolic activities
Liver abnormalities in thyroid disease
Diminished lipid metabolism>
Hepatic steatosis
Liver abnormalities in hypothyroidism
(ALT)
(AST)
(GGT)
Bilirubin
(LDH)
high
(N/high
------
high
N/high
Hypothyroidism-induced myopathy
Diminished lipid metabolism
High Cholestasis
Hepatic steatosis
----------
Hypothyroidism-induced myopathy
The role of hypothyroidism in (NAFLD)
The prevalence of NAFLD seems to be inversely related to FT4 levels;
decreased serum FT4 concentrations increase the risk of NAFLD in a dose-dependent manner.
Rotterdam Study, showing that in the general population even subclinical hypothyroidism is associated with an increased risk of developing NAFLD and fibrosis.
hypothyroidism-related NAFLD might be a distinct and potentially curable disease
The role of hypothyroidism in gallstone disease
Hypothyroidism may favor gallstone formation through three different mechanisms:
(2) hypercholesterolemia, characterized by higher concentrations of both total cholesterol and LDL cholesterol;
(3) hypotonia of the gallbladder causing delayed emptying of the biliary tract.
it is advisable that all patients (especially women) > 60 years of age with common bile duct stones be screened for thyroid dysfunction.
Clinical features shared by overt hypothyroidism and hepatic failure
hyperammonemia in severe hypothyroidism
Hypothyroidism increase urea synthesis enhancing proteolysis
and affecting urea metabolism .
decreased intestinal motility due to hypothyroidism,which might favor bacterial production and absorption of ammonia,
and the decreased glutamine synthetase activity,
which might reduce glutamine utilization by the urea cycle in the liver.
Hyperammonemic coma revert after restoration of euthyroidism.
thyroid function should be assessed in patients with well-compensated liver cirrhosis, normal liver synthetic function, and apparent hepatic encephalopathy that is refractory to lactulose treatment:
the lack of effect of lactulose might be related to gastrointestinal hypomotility associated with hypothyroidism.
Myxedema ascites
altered capillary permeability
the decreased lymphatic drainage.
Restoration of euthyroidism leads to resolution of ascites
Increased oxygen consumption,
with relative hypoxia
leading to apotosis and oxidative stress
Liver abnormalities in hyperthyroidism
(ALT)
GGT)
Bilirubin
LDH)
high
high
high
high
Cholestasis
Enhanced osteoblastic activity
Cholestasis
(if high levels of GGT and bilirubin coexist)
Cholestasis
(AST)
(ALP)
high
hormone-induced cholestasis
osteoblastic activity
At light microscopy common findings are non-specific:
mild lobular inflammatory infiltrate,
nuclear irregularities,
and Kupffer cell hyperplasia.
electron microscopy may show hyperplasia of the smooth endoplasmic reticulum,
reduced cytoplasmic glycogen,
and an increase in mitochondria size and number.
If hyperthyroidism is severe, hepatic damage may be worse, leading to centrizonal necrosis and perivenular fibrosis.
clinical features may include
deep jaundice,
coagulopathy,
hepatomegaly,
and even ascites due to sinusoidal congestion
and exudation of protein-rich fluid into the space of Disse
A case report of severe neonatal hyperthyroidism
due to maternal Graves’ disease,
causing liver failure,
but promptly responsive to carbimazole.
autoimmune thyroid disease (Graves’ disease),
could also be associated with autoimmune hepatobiliary diseases,
such as primary biliary cirrhosis
and autoimmune hepatitis .
prompt restoration of euthyroidism, reverts liver function abnormalities.
Thyroid cancer
(DTC) are rare.
Liver masses do not uptake radioiodine;
Functional metastases are rare.
highly aggressive .
Liver abnormalities due to thyroid disease�treatment
Thyroid hormone medication
immunoallergic hepatitis or hypersensitivity reactions to levothyroxine associated with liver enzyme increase and mild jaundice have been observed.
case of a hypothyroid patient, in whom liver dysfunction occurring during replacement treatment (associated with detection of serum antibodies to T4) improved after switching from LT4 to T3.
Antithyroid drugs
propylthiouracil (PTU), methimazole (MMI),
The overall incidence less than 0.5%
severe liver injury appears to be more frequent using PTU,
autoimmune or idiosyncratic reaction.
PTU
dose independent.
more frequently within 3 months after the initiation of treatment.
Moderate increase in serum AST and ALT (hepatocellular toxic
pattern), and bilirubin.
remit spontaneously
may progress to hepatic failure and overt jaundice.
PTU is the third medication most strongly linked to liver transplant,
and mortality from PTU-induced hepatotoxicity is around 25%.
MMI
very rare.
older than 40 years.
dose-dependent.
Intrahepatic cholestatic pattern, with expanded portal tracts, inflammatory cells infiltration, proliferating cholangioles and bile plugs
Treatment
Ursodeoxycholic acid.
few cases treated with steroids.
Radioiodine treatment
hepatic dysfunction occurred after RAI treatment for Graves’ disease.
in the presence of thyrotoxicosis, which is quite common in
the immediate post-RAI period, particularly if the patient
is not pretreated with ATDs.
Two weeks after ablative therapy,
a marked increase in liver enzyme concentrations occurred,
abdominal ultrasonography showed prominent periportal
interstitial echogenicity,
and liver biopsy showed moderate lobular inflammation and a mild portal inflammation without fibrosis
An increased hepatic iodine uptake, due to
the absence of thyroid gland, might explain liver damage
in these cases.