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Effect of Levothyroxine Replacement on Lipid Profile and Intima-Media Thickness in Subclinical Hypothyroidism: A Double-Blind, Placebo- Controlled Study

Department of Internal Medicine and National Research Council Institute of Clinical Physiology, University of Pisa, Pisa 56126, Italy

Address all correspondence and requests for reprints to: Fabio Monzani, M.D., Metabolism Unit, Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. E-mail: fmonzani{at}med.unipi.it.

Subclinical hypothyroidism (sHT) is associated with dyslipidemia and enhanced cardiovascular risk. We assessed carotid artery intima-media thickness (IMT, high-resolution ultrasonography) and lipoprotein profile in 45 sHT patients (aged 37 ± 11 yr) at baseline and after 6 months of randomized, placebo-controlled L-T₄ replacement. In comparison with 32 age- and sex-matched controls, sHT patients had elevated total and low-density lipoprotein (LDL) cholesterol and ApoB levels (P = 0.002, P = 0.0007, and P = 0.01, respectively) and higher mean-IMT values (P < 0.0001). In stepwise regression analysis, mean-IMT was positively related (r² = 0.71, P < 0.0001) to age, TSH, and LDL cholesterol. L-T₄ replacement significantly reduced both total and LDL cholesterol (P < 0.0001 for both) and mean-IMT (by 11%, P < 0.0001). The decrement in IMT was directly related to the decrements of both total cholesterol and TSH (P = 0.02 and P = 0.0001, respectively). We conclude that early carotid artery wall alterations are present in sHT patients. Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall cannot be clearly decided on the basis of the present results. However, the fact that L-T₄ replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in subclinical hypothyroidism.

The study was partly presented at the Annual Meeting of the European Thyroid Association, Edinburgh, United Kingdom, October 18–22, 2003.

Abbreviations: ApoA₁, Apolipoprotein A₁; ApoB, apolipoprotein B; BMI, body mass index; CI, confidence interval; FT₃, free T₃; FT₄, free T₄; IMT, intima-media thickness; IRMA, immunoradiometric assay; LDL, low-density lipoprotein; LDLc, LDL cholesterol; Lp(a), lipoprotein(a); L-T₄, levothyroxine; sHT, subclinical hypothyroidism; TC, total cholesterol; TG, triglyceride; Tg-Ab, antithyroglobulin autoantibody; tHcy, total homocysteine; TPO-Ab, antithyroid peroxidase autoantibody; VSM, vascular smooth muscle.

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