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Cited by 431Thyroid Disorders and TreatmentsNitric Oxide and Endothelin EffectsCardiovascular Health and Disease Prevention

Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy

Taddei, Stefano, Caraccio, Nadia, Virdis, Agostino, Dardano, Angela, Versari, Daniele, Ghiadoni, Lorenzo, Salvetti, Antonio, Ferrannini, Ele +1 more·2003·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2003-030039
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Abstract

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.

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  • Hyperlipidemia and thyroid antibodies are thought to reduce endothelial nitric oxide synthase expression, impairing vasodilation.

    “Both hyperlipidemia and thyroid antibodies are thought to reduce expression of endothelial nitric oxide synthase, thereby impairing vasodilation (15).”

    From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [15]

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Authors
Taddei, S., Caraccio, N., Virdis, A., Dardano, A., Versari, D., Ghiadoni, L., Salvetti, A., Ferrannini, E., & Monzani, F.
Affiliations
University of Pisa (IT)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2003-08-01
Volume
88
Issue
8
Pages
3731-3737
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2003-030039
OpenAlex
W2060930755
Cited by
431
References
43
Citations by year
2026: 8 · 2025: 6 · 2024: 14 · 2023: 15 · 2022: 24 · 2021: 14 · 2020: 27 · 2019: 19 · 2018: 19 · 2017: 12 · 2016: 24 · 2015: 17 · 2014: 34 · 2013: 26 · 2012: 26
FWCI
9.77
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
subclinical hypothyroidism, endothelial dysfunction, endothelium-dependent vasodilation, nitric oxide bioavailability, levothyroxine, acetylcholine, L-NMMA, forearm blood flow, dyslipidemia, cardiovascular risk, sodium nitroprusside
MeSH terms
Acetylcholine, Adult, Endothelium, Vascular, Enzyme Inhibitors, Female, Humans, Hypothyroidism, Iodide Peroxidase, Lipids, Lipoproteins, LDL, Male, Nitric Oxide, Nitroprusside, Regional Blood Flow, Thyroglobulin, Thyroid Hormones, Thyroiditis, Autoimmune, Thyroxine, Vascular Resistance, Vasodilation, Vasodilator Agents, Nitric Oxide Synthase, omega-N-Methylarginine, Nitric Oxide Donors, Nitric Oxide Synthase Type III

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