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Impaired Endothelium-Dependent Vasodilatation in Subclinical Hypothyroidism: Beneficial Effect of Levothyroxine Therapy

Department of Internal Medicine, University of Pisa, 56100 Pisa, Italy

Address all correspondence and requests for reprints to: Stefano Taddei, M.D., Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail: s.taddei{at}med.unipi.it.

Subclinical hypothyroidism (sHT) is associated with enhanced cardiovascular risk. To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide (NO) availability, in 14 patients [serum cholesterol, 218 ± 41 mg/dl (5.6 ± 0.9 mM)] and 28 euthyroid subjects, subdivided into groups A and B [serum cholesterol, 170 ± 19 mg/dl (4.4 ± 0.5 mM) and 217 ± 21 mg/dl (5.6 ± 0.5 mM), respectively], we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine, an endothelium-dependent vasodilator, at baseline and during infusion of N^G-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor. Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated. In sHT patients, vasodilation to acetylcholine was reduced, compared with group B (+358 ± 29% vs. +503 ± 19%, P = 0.0003) and group A (663 ± 65%, P = 0.02 vs. group B and P = 0.0002 vs. sHT). L-NMMA blunted the vasodilation to acetylcholine in groups A and B (49.1 ± 6.3% and 42.7 ± 5.5% maximal forearm blood flow reduction, respectively, P < 0.0001 vs. acetylcholine), whereas it was ineffective in sHT patients (12.8 ± 2.5%). Response to sodium nitroprusside and minimal vascular resistances were similar. In sHT (n = 9) patients, 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition. Patients with sHT are characterized by endothelial dysfunction resulting from a reduction in NO availability, an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation.

Abbreviations: ApoB, Apolipoprotein B; BMI, Body mass index; ESR, erythrocyte sedimentation rate; FBF, forearm blood flow; FT, free thyroid hormone; HDL, high-density lipoprotein; Lp (a), Lipoprotein (a); L-NMMA, N^G-monomethyl-L-arginine; L-T₄, levothyroxine_; LDL, low-density lipoprotein; MFVRs, minimal forearm vascular resistances; NO, nitric oxide; sHT, subclinical hypothyroidism; Tg-Ab, antithyroglobulin; TPO-Ab, antithyroid peroxidase.

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