Effect of Thyroxine Therapy on Serum Lipid Levels in Subclinical Hypothyroidism

Summary

A systematic review 1 included 13 studies with a total of 247 subjects with mild thyroid failure (i.e. subclinical hypothyroidism). Three studies (23%) were RCTs with 81 participants. The mean decrease in the serum total cholesterol (TC) concentration (13 studies) was -0.20 mmol/l (-7.9 mg/dl, 95% CI -0.09 to 0.34). The decline in serum TC was directly proportional to its baseline concentration. Studies enrolling hypothyroid participants receiving suboptimal T4 doses reported significantly larger decreases in serum TC after thyroid-stimulating hormone normalisation than those enrolling previously untreated individuals with mild thyroid failure. The authors conclude the reduction in serum TC may be larger in individuals with higher pre-treatment cholesterol levels, and in hypothyroid individuals taking suboptimal T4 doses. There seems to be no significant effects of T4 on serum HDL or triglyceride concentrations.

Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 ± 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk 2. In the L-thyroxine group (n = 31) TC and low density lipoprotein cholesterol (LDL-C) were significantly reduced (-0.24 mmol/liter, 3.8%, P = 0.015) and -0.33 mmol/liter, 8.2%, P = 0.004), respectively). LDL-C decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated LDL-C levels at baseline. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02).

A systematic review 3 included 12 studies with a total of 940 subjects with subclinical hypothyroidism. Levothyroxine substitution reduced TC (WMD-0.29 mmol/L, 95% CI -0.42 to -0.16) and LDL-C (WMD -0.22 mmol/L, 95% CI -0.36 to -0.09, statistical heterogeneity I² =66%), with no significant effects on HDL-C (-0.04 mmol/L, 95% CI -0.08 to 0.01; statistical heterogeneity I² =64%) or triglycerides (-0.04 mmol/L, 95% CI -0.08 to 0.00). Studies in which only patients with mild subclinical hypothyroidism (TSH <10 mIU/L) were enrolled showed similar results.