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TSH-Controlled L-Thyroxine Therapy Reduces Cholesterol Levels and Clinical Symptoms in Subclinical Hypothyroidism: A Double Blind, Placebo-Controlled Trial (Basel Thyroid Study)

Divisions of Endocrinology (C.M., J.J.S., C.B.R., M.G., M.K., A.R.M., B.M.) and Clinical Pharmacology (J.D.), and Department of Central Laboratories (P.H.), University Hospital Basel, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Dr. C. Meier, Division of Endocrinology, Department of Internal Medicine, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: cmeier{at}uhbs.ch

Abstract

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. 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. Individual L-thyroxine replacement (mean dose, 85.5 ± 4.3 µg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 ± 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (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 effect on low density lipoprotein 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 lipoprotein cholesterol.

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