TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinicalsymptoms in subclinical hypothyroidism: A double blind, placebo-controlledtrial (basel thyroid study)

This study evaluated the effect of physiological, TSH-guided, L-thyroxine t reatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TS H, 11.7 +/- 0.8 mIU/ liter) were randomly assigned to receive L-thyroxine o r placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/ - 4.3 mug/d) was performed based on blinded TSH monitoring, resulting in eu thyroid TSH levels (3.1 +/- 0.3 mIU/ liter). Lipid concentrations and clini cal scores were measured before and after treatment. Sixty-three of 66 pati ents completed the study. In the L-thyroxine group (n = 31) total cholester ol and low density lipoprotein cholesterol were significantly reduced [-0.2 4 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), resp ectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low dens ity lipoprotein cholesterol levels at baseline. A significant decrease in a polipoprotein B-100 concentrations was observed (P = 0.037), whereas high d ensity lipoprotein cholesterol, triglycerides, apolipoprotein Al, and lipop rotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved signi ficantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial e ffect on low density lipo. protein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lip oprotein cholesterol.