Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study

The relationship between subclinical hypothyroidism (SCH) and an atherogenic lipoprotein profile is still controversial. We measured lipoproteins in 49 SCH patients by comparison with 33 euthyroid controls. Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDLc), apolipoprotein A(1), apolipoprotein B, and lipoprotein (a) [Lp(a)] were measured after an overnight fast. Patients were randomly assigned to levothyroxine therapy or placebo and re-evaluated after 6 months of euthyroidism. SCH patients showed significantly higher TC (P < 0.01), LDLc (P = 0.01), and apolipoprotein B (P = 0.001) levels than controls, positively correlated with baseline TSH levels (P = 0.003, P = 0.01, and P = 0.03, respectively). Elevated Lp(a) levels were significantly more frequent in SCH (P < 0.05) and associated with familial diabetes mellitus and/or coronary heart disease (P < 0.01). Levothyroxine treatment resulted in a significant decrease of both TC and LDLc concentrations (P = 0.003), in direct proportion to the respective baseline values (P < 0.05 and P < 0.01, respectively), whereas no change in Lp(a) level was observed. No changes occurred in the placebo group. In conclusion, only serum LDLc levels are increased specifically and reversibly in association with SCH. Altered Lp(a) values reflect a genetic influence rather than a reduced thyroid hormone action.