Hepatic conversion of amino nitrogen to urea nitrogen in hypothyroid patients and upon l-thyroxine therapy

Abstract

Conflicting studies have been reported regarding the influence of thyroid hormones on hepatic nitrogen metabolism and liver metabolic activity. We studied urea N synthesis rate (UNSR), functional hepatic N clearance (FHNC), galactose elimination capacity, and antipyrine clearance in six hypothyroid female patients before and after achievement of a stable euthyroid status. In both conditions, UNSR measured at intervals in response to constant alanine infusion was linearly related to the average α-amino N concentrations. In the hypothyroid state, peak UNSR was decreased by 31% in comparison with values measured in euthyroidism, which were in the normal range. FHNC (ie, the slope of the linear relation between UNSR and blood α-amino N concentration) is a measure of the kinetics of the process of hepatic amino N to urea N conversion; it was 19.8 ± 4.0 L · h −1 in hypothyroid patients and increased to normal values after l-thyroxine replacement (30.4 ± 3.3 L · h −1, P < .01; normal values > 25 L · h −1). Hepatic microsomal and cytosolic activities (antipyrine clearance and galactose elimination) were normal in hypothyroid patients and did not change significantly after therapy. Our data show a specific defect in hepatic handling of amino acids in hypothyroid patients, leading to reduced α-amino N to urea N conversion, in the absence of any detectable impairment in different hepatic metabolic activities.