Changes in Liver Function correlate with the Improvement of Lipid Profile after Restoration of Euthyroidism in Patients with Subclinical Hypothyroidism

Overt hypothyroidism frequently leads to liver dysfunction. Subclinical hypothyroidism (SCH) is linked to abnormalities of lipoprotein metabolism, however, data on liver function are lacking. We analyzed the effects of L-thyroxine (L-T4) therapy on liver function and their association with changes of serum lipoproteins in SCH as part of a prospective, double-blind study. 66 women with SCH were randomly assigned to receive either L-thyroxine or placebo for 48 weeks. Circulating liver and biliary enzymes as well as serum lipid levels were assessed at baseline and after 24 and 48 weeks. Alkaline phosphatase as parameter of hepato-biliary function increased after 48 weeks of L-T4 treatment (p=0.004). Circulating levels of alanine amino transferase (ALT) and serum aspartate transferase (AST) did not change during L-T4 treatment. However, there was a correlation between both, ∆AST and ∆ALT with ∆-total cholesterol (r=0.60, p<0.001 and r=0.52, p=0.002, respectively). Similarly, both, ∆AST and ∆ALT, correlated with ∆LDL cholesterol (LDL-C), respectively. Consecutively, patients with marked decrease of serum lipids during L-T4 therapy had a significantly higher decrease in AST and ALT, respectively, as compared to patients without amelioration of the lipid profile. Thyroid hormone replacement in SCH affects biliary tract function, yet, has no overall effect on hepatocellular enzymes. The relatively strong correlation between changes of serum AST and ALT with changes of LDL-C levels suggests that the mechanism of decreased LDL-C observed in restoration of euthyroidism in patients with SCH might be caused in part by changes of hepatic lipoprotein catabolism and a restored hepato-cellular function.