Thyroid function in chronic liver disease

There is a recent hypothesis that thyroxine (T4), secreted by the thyroid gland under physiological conditions, is mono-deiodinated in extrathyroidal sites to form the more active 3, 3', 5-tri-iodothyronine (T3) before exerting biological activity at target tissue level. Futhermore, circumstantial evidence suggests that the liver is an important site for the extra-thyroidal conversion of T4 to T3. Thyoid hormone pathophysiology in liver disease is therefore of interest. Patients with hepatic cirrhosis have normal or raised plasma T4 concentration and markedly reduced plasma T3 concentration. Free hormone measurement reflect this pattern and three is kinetic and other evidence to support the concept that extra-thyroidal conversion of T4 to T3 is reduced in patients with liver dysfunction. Comparable finding have however been reported in patients with other non-hepatic chronic systemic diseases but, unlike in hepatic cirrhosis, serum thyrotropin (TSH) is not increased. Increased serum TSH is found in hepatic cirrhois and is often accompanied by an abnormal TSH response to thyrotropin-releasing hormone (TRH) suggesting, in addition, disordered hypothalamic-pituitary control of thyroid function in these patients. Thyroid physiology is clearly markedly disturbed in hepatic cirrhosis but no single hypothesis adequately accounts for all the observed abnormalities. The recent finding of increased plasma 3, 3', 5-tri-iodothyronine (reverse t3; rT3) concentration in hepatic cirrhosis may ulimately clarify our understanding.