Low normal thyroid function attenuates serum alanine aminotransferase elevations in the context of metabolic syndrome and insulin resistance in white people

Objectives: Thyroid hormones play a key role in hepatic lipid metabolism. Although hypothyroidism is associated with increased prevalence of non-alcoholic fatty liver disease (NAFLD), the relationship of NAFLD with low normal thyroid function is unclear. We tested the association of serum alanine transferase (ALT), as a surrogate of NAFLD, with variations in thyroid function within the normal range.

Design and methods: Thyroid stimulating hormone (TSH), free T4, ALT, insulin resistance (homeostasis model assessment (HOMA-IR)) and adiponectin were measured in 82 non-diabetic white subjects with TSH and free thyroxine (free T4) levels within the reference range. Nineteen participants were classified with metabolic syndrome (MetS).

Results: ALT was higher in MetS subjects (p<0.05), coinciding increased HOMA-IR (p<0.001). TSH and free T4 levels were not different in subjects with and without MetS. In all subjects combined, ALT was correlated positively with HOMA-IR and inversely with adiponectin (both p<0.001). Remarkably, ALT was correlated inversely with TSH in subjects with MetS (r=-0.642, p=0.003), but not in subjects without MetS (r=-0.132, p=0.30). Accordingly, in age- and sex-adjusted multivariable linear regression analysis the relationship of ALT with TSH was modified by the presence of MetS (interaction: β=-0.244, p=0.026), and likewise by HOMA-IR (interaction: β=-0.203, p=0.037). TSH also interacted with adiponectin on ALT (interaction: β=0.204, p=0.037).

Conclusions: Low normal thyroid function may attenuate ALT elevations in the context of MetS and insulin resistance. It is conceivable that effect modification of low normal thyroid function on adiponectin-mediated pathways may be involved.