The DOI matches its Crossref record; 41 of the 43 references it cites were found in a registry or an index.
Impaired Endothelium-Dependent Vasodilatation in Subclinical Hypothyroidism: Beneficial Effect of Levothyroxine Therapy
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Furchgott, R. F., & Zawadzki, J. V. (1980) · Nature · doi:10.1038/288373a0 · Cited by 12,064
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · cited 1×
“The most important vasodilator substance produced by the endothelium is nitric oxide (NO) (18, 19), derived from the conversion of l-arginine into citrulline via the activity of the enzyme NO-synthase (20).”
BackgroundVascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
Schächinger, V., Britten, M. B., & Zeiher, A. M. (2000) · Circulation · doi:10.1161/01.cir.101.16.1899 · Cited by 2,589
Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase
Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C. J., Reed, R. R., & Snyder, S. H. (1991) · Nature · doi:10.1038/351714a0 · Cited by 2,354
Long-Term Follow-Up of Patients With Mild Coronary Artery Disease and Endothelial Dysfunction
Suwaidi, J. M. S. A., Hamasaki, S., Higano, S. T., Nishimura, R. A., Holmes, D. R., & Lerman, A. (2000) · Circulation · doi:10.1161/01.cir.101.9.948 · Cited by 2,044
Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T., & Münzel, T. (2001) · Circulation · doi:10.1161/hc4601.099485 · Cited by 1,961
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Vallance, P., Collier, J., & Moncada, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91013-1 · Cited by 1,590
The measurement of volume changes in human limbs
Whitney, R. J. (1953) · The Journal of Physiology · doi:10.1113/jphysiol.1953.sp004926 · Cited by 1,496
Flagged first, then by citations
2 of the 43 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Folkow, 1995, The structural factor in hypertension with special emphasis on the altered geometric design of the systemic arteries, In: Laragh JH, Brenner BM, eds. Hypertension: pathophysiology, diagnosis and treatment. New York: Raven Press;, 481
Cited by
Sorted by citations
Items 401–430 of 430
Influência do exercício físico nas alterações cardiovasculares induzidas pelo hipotireoidismo
de Souza, A. A., Lima, A. H. R. D. A., da Nóbrega, T. K. S., & Silva, A. S. (2012) · Revista Brasileira de Atividade Física & Saúde · doi:10.12820/2317-1634.2012v17n5p370
Relationship between vitamin D and autoimmune Hashimoto’s thyroiditis in Gharbiya Governorate
Shazly, H. N. E., Shalaby, K. H., Mohammed, W. S., & Ibrahem, I. A. W. (2021) · Tanta Medical Journal · doi:10.4103/tmj.tmj_194_20
Mukhopadhyay, M., Sahai, S. S., Kar, A., Chatterjee, N., Sengupta, N., & Banerjee, S. (2022) · INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH · doi:10.36106/ijsr/2606142
Maternal Thyroid Function Tests between 11 and 13 Weeks of Pregnancy as a Predictor of Preeclampsia
MONSEF, H. E. A. E., & AZEZ, M. D. M. K. E. H. A. F. E. (2022) · The Medical Journal of Cairo University/The Medical Journal of Cairo University · doi:10.21608/mjcu.2022.264491
Maghami, Z. G., Alizadehasl, A., Khalili, N., Khalili, Y., Sadeghpour, A., Maharlou, M., & Rahbar, Z. (2022) · Multidisciplinary Cardiovascular Annals · doi:10.5812/mca-128541
Zhao, M., Zeng, Z., He, Q., Wang, R., Zhang, M., Ruan, B., & Chen, P. (2022) · Research Square · doi:10.21203/rs.3.rs-2127874/v1
Al-majedy, K. M. M. (2021) · University of Thi-Qar Journal of Science · doi:10.32792/utq/utjsci.v8i2.812
Hypothyroidism Among Diabetic Pregnancy and its Effect on Maternal and Fetal Outcome
Sharmin, F., Rahman, N., & Momotaz, P. (2023) · Annals of International medical and Dental Research · doi:10.53339/aimdr.2023.9.1.12
PECULIARITIES OF THE COURSE OF CARDIOVASCULAR PATHOLOGY IN SUBCLINICAL HYPOTHYROIDISM
Kuznetsova, O. E., Kruzhalin, E. E., Кутелев, Г. Г., Cherkashin, D. V., & Nikashin, A. N. (2023) · Translational Medicine · doi:10.18705/2311-4495-2023-10-3-209-222
Late metabolic consequences of childhood cancer
Pluimakers, V. G. (2023) · Utrecht University Repository (Utrecht University) · doi:10.33540/1778
Elmas, B., Koçer, G. B., Bal, C., Nural, C., & Yılmaz, G. (2023) · Sakarya Medical Journal · doi:10.31832/smj.1386547
Hsu, C., Lin, C.-H., Liu, P., & Lin, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-3932875/v1
Studies on Serum T3, T4, TSH, Progesterone and Oestrogen in Cardiovascular Disease Patients
Nnadi, P. H., Nwachukwu, M., Ikaraoha, I. C., Mbachu, J. W., Mmerenini, K. A., Ndubueze, C. W., & Iwuji, C. C. (2024) · International Journal of Biochemistry Research & Review · doi:10.9734/ijbcrr/2024/v33i2856
Abate, E. G., Sharma, S., Barsukova, Y., & GOSWAMI, R. M. (2024) · JHLT Open · doi:10.1016/j.jhlto.2024.100111
Muntean, M., Săsăran, V., Pop, L. G., Elena, M. I., Rus, V. A., & Claudiu, M. (2024) · Biomedicines · doi:10.3390/biomedicines12112587
Subklinik Tiroid Hastalarında Metabolik Sendrom Sıklığı
Kösemehmetoğlu, Ö. S., & Eskioğlu, E. (2024) · Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Dergisi · doi:10.17517/ksutfd.1466604
Ceylan, Ş. (2024) · Medical Science and Discovery · doi:10.36472/msd.v11i12.1237
Businge, C. B., & Longo‐Mbenza, B. (2025) · Pathophysiology · doi:10.3390/pathophysiology32020018
Zhang, M., Luo, C., Wang, J., Wang, J., Ruan, B., Hou, P., & Chen, P. (2025) · Scientific Reports · doi:10.1038/s41598-025-31396-1
“Levothyroxine supplementation has been shown to ameliorate atherosclerosis and endothelial dysfunction in patients with subclinical hypothyroidism 22–24 .”
He, H., Zhang, Z., Xia, L., Cui, C., Jiang, M., Feng, Q., Peng, X., Feng, J., Jia, D., Luo, Y., et al. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1696692
Chen, Z., Alifu, X., Li, W., & Yu, Y. (2025) · Research Square · doi:10.21203/rs.3.rs-8051840/v1
Hsu, C.-W., Lin, C.-H., Liu, P., & Lin, Y.-H. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1721865
Wen, J., Hu, J., & Zou, G. (2026) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-026-01931-6
“In contrast, hypothyroidism facilitates IHD progression mainly through detrimental changes in lipid metabolism—such as elevated total cholesterol and LDL levels—diastolic hypertension, and impaired endothelial vasodilation resulting from decreased nitric oxide bioavailability [20].”
Zhong, J., Dai, L., Lu, X., Ruan, J., Li, Y., Lu, Y., & Chen, Y. (2026) · Research Square · doi:10.21203/rs.3.rs-10230639/v1
Congenital Hypothyroidism and Atherosclerosis: An Endocrine Model of Early-Life Cardiovascular Risk
Tzoraki, M., & Duntas, L. H. (2026) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd13080369
“In hypothyroid states, reduced NO bioavailability and increased vascular tone contribute to endothelial dysfunction and arterial stiffness, both of which represent early functional changes in atherogenesis [12].”
Gatta, E., Delbarba, A., Vizzardi, E., Rotondi, M., & Cappelli, C. (2026) · Endocrine · doi:10.1007/s12020-026-04745-x
Gallo, D., Piantanida, E., Guasti, L., & Tanda, M. L. (2026) · L Endocrinologo · doi:10.1007/s40619-026-01871-6
Liu, W., Wang, M., Jiang, H., Chen, L., Hu, X., Ye, J., Rao, W., Zhang, J., Yan, W., Wu, W., et al. (2026) · Translational Vision Science & Technology · doi:10.1167/tvst.15.10.29
“21,31 20”
França, M. M. (2013) · Americanae (AECID Library)
Cardiac Morphology and Function in Mild Hypothyroidism
Biondi, B. (2009) · Springer eBooks · doi:10.1007/978-88-470-1143-4_3
“Finally, like overt hypothyroidism, subclinical hypothyroidism was associated with endothelial dysfunction [36, 37] due to impaired availability of nitric oxide.”
Background
Metadata
- Authors
- Taddei, S., Caraccio, N., Virdis, A., Dardano, A., Versari, D., Ghiadoni, L., Salvetti, A., Ferrannini, E., & Monzani, F.
- Affiliations
- University of Pisa (IT)
- 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
- 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 (medical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
