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The Beneficial Effect of L-Thyroxine on Cardiovascular Risk Factors, Endothelial Function, and Quality of Life in Subclinical Hypothyroidism: Randomized, Crossover Trial

Departments of Endocrinology (S.R., L.I., J.U.W.) and Biochemistry (G.K.), Queen Elizabeth Hospital, Gateshead NE9 6SX, United Kingdom; Department of Regional Medical Physics (C.O.), Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom; Department of Psychology (C.M.), Health Psychology Research, Royal Holloway, University of London, Egham TW20 0EX, United Kingdom; and Department of Diabetes and Endocrinology (S.R., J.U.W.), School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom

Address all correspondence and requests for reprints to: Dr. J. U. Weaver, Ph.D., F.R.C.P., School of Clinical Medical Sciences, Department of Diabetes and Endocrinology, University of Newcastle, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. E-mail: j.u.weaver{at}ncl.ac.uk.

Context: Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life.

Objective: The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment.

Design: This was a randomized, double-blind, crossover study of L-thyroxine and placebo.

Setting: The study was conducted with community-dwelling patients.

Patients: One hundred patients [mean age (SD) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease.

Intervention: Intervention consisted of 100 µg L-thyroxine or placebo daily for 12 wk each.

Measurements: Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed.

Results: L-thyroxine treatment reduced TC (vs. placebo) from 231.6 to 220 mg/dl, P < 0.001; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl, P < 0.05; waist to hip ratio from 0.83 to 0.81, P < 0.006; and improved FMD from 4.2 to 5.9%, P < 0.001. Multivariate analysis showed that increased serum free T₄ level was the most significant variable predicting reduction in TC or improvement in FMD. Furthermore, the symptom of tiredness improved on L-thyroxine therapy, but other patient-reported outcomes were not significantly different after correction for multiple comparisons.

Conclusion: SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T₄ concentration.

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