Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis.

Abstract

A B S T R A C T The role of liver in the peripheral conversion of thyroxine (T4) to triiodothyronine (Ts) was studied in normal subjects and patients with alcoholic liver disease by measurement of thyrotrophin (TSH) and total and free T4 and T3 in random and serial serum samples. Also, T4 to Ts conversion rates and Ts disposal rates were compared by noncompartmental analysis. While the mean total serum T4 values were similar for the two groups, 8.6 and 8.1 ug/dl, the mean free To value was significantly higher in the cirrhotic patients (3.3 ng/dl) than in the normal subjects (2.1 ng/dl, P < 0.001). The mean serum T3 value, 85 ng/dl, was significantly reduced in the hepatic patients as compared to a mean serum T8 value of 126 ng/dl in the normal subjects (P < 0.001), while the free T3 value was 0.28 ng/dl in both groups. The reduction of the serum total and free Ts values were closely correlated with the degree of liver damage, as indicated by elevation of serum bilirubin (r = -0.547) and reduction of serum albumin (r = 0.471). The mean serum TSH level was 3.1 AiU/ml in the normals and 7.1 tU/ ml in the cirrhotic patients (P < 0.001). 15% of the hepatic patients had serum TSH values above 10 AU/ ml, which, however, did not correlate with any of the four liver function tests studied. Serial blood sampling from two convalescing patients with alcoholic hepatitis showed a gradual normalization of serum TSH and Ts levels as the liver function improved. After oral T4 administration, 0.25 mg/day for 10 days, three of four cirrhotic patients studied failed to raise their serum Ts values. The mean T4 to Ts conversion rate of seven normal subjects was 35.7%. The mean T4 to T3 conversion rate of four cirrhotic patients studied was significantly reduced to 15.6% (P < 0.001). The mean Received for publication 12 March 1974 and in revised form 22 May 1975. disposal rates of T4 and T3 of the normal subjects were 114 and 34 ,ig/day, respectively. The ratio of T, disposal to T3 disposal was 3.5. In contrast, the mean T4 disposal rate, 82 Ag/day, and the mean Ts disposal rate, 10 ug/day, were both reduced in the cirrhotic patients. Their ratio of T4 disposal to Ts disposal was 7.9. These findings suggest that impairment of T4 conversion in patients with advanced hepatic cirrhosis may lead to reduced Ts production and lowered serum Ts level. Therefore, the liver is one of the major sites of T4 conversion to Ts.

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

“…Others have also observed low normal or low in hepatic cirrhosis patients studied here. As against PR-rT3, PR-T3 in patients with hepatic cirrhosis was clearly subnormal; another recent study has also described low PR-T3 in hepatic cirrhosis (25). PR-T3 was low in patients in this study whether it was examined as such (Table II) or in relation to PR-T4 (Fig.…”

“…Meanwhile, it is interesting to note that serum rT3 as well as T3 return to or towards normal after refeeding of patients with protein-calorie malnutrition (9) and starvation (2). Improvement in low serum T3 has also been observed after recovery of liver function in patients with alcoholic hepatitis (25). These findings suggests that the abnormality of T4 metabolism in illness and starvation is frequently reversible.…”

Formation of diiodotyrosine from thyroxine. Ether-link cleavage, an alternate pathway of thyroxine metabolism.

“…For example, under certain circumstances, the sum of the apparent production rates of T3 and rT3 is far less than the overall rate of deiodination of T4. This is characteristically true in several clinical conditions that lead to impaired peripheral production of T3, such as starvation (28,29), and hepatic cirrhosis (30,31). Here, the overall degradation of T4 is unchanged and T3 production is markedly reduced, while rT3 production rates are only slightly increased, findings that suggest that T4 metabolism has been diverted to other pathways.…”

Thyroid Hormone Levels in Children With Liver Cirrhosis Awaiting a Liver Transplant

“…[1][2][3][4] In some studies of liver cirrhosis where the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) have been examined, the liver was found a major site of this peripheral conversion. 5 The liver metabolizes thyroid hormones and regulates their systemic endocrine effects; therefore, liver diseases could affect thyroid hormone metabolism.…”