Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine

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Abstract

Background:

Subclinical hypothyroidism (SHT) may increase the risk of cardiovascular disease. We compared endothelial function between SHT patients and euthyroid individuals, and evaluated the effects of levothyroxine therapy on endothelial function in the patients.

Materials and Methods:

In a quasi-experimental study, flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in SHT patients and healthy controls ( n = 25 in each group). Patients then received levothyroxine (50 μg/day) for 2 months, and the FMD and IMT assessments were repeated.

Results:

Patients and controls were similar in IMT (0.56 ± 0.09 vs. 0.58 ± 0.08 mm, P = 0.481), but FMD was lower in patients than in controls (4.95 ± 2.02 vs. 6.50 ± 2.57%, P = 0.011). A significant increase was observed in FMD (4.11 ± 2.37%, P = 0.001), but not in IMT (−0.004 ± 0.020 mm, P = 0.327), after levothyroxine therapy among the patients.

Conclusions:

Patients with SHT have endothelial dysfunction which responds to levothyroxine therapy. Randomized placebo-controlled trials are needed to confirm these findings.

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Most cited references 22

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Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.

A. Hak, H. A. Pols, T J Visser … (2000)

Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial. To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women. Population-based cross-sectional study. A district of Rotterdam, The Netherlands. Random sample of 1149 women (mean age +/- SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study. Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result. Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took beta-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease. Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.

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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.

Salman Razvi, Andrew Oates, Lorna Ingoe … (2007)

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. The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. This was a randomized, double-blind, crossover study of L-thyroxine and placebo. The study was conducted with community-dwelling 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 consisted of 100 microg L-thyroxine or placebo daily for 12 wk each. 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. 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 T(4) 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. 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 T(4) concentration.

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Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death.

H. B. Newman, Nathalie De Geyter, Richard Harris … (2005)

Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.

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Author and article information

Journal

Journal ID (nlm-ta): Adv Biomed Res

Journal ID (iso-abbrev): Adv Biomed Res

Journal ID (publisher-id): ABR

Title: Advanced Biomedical Research

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Electronic): 2277-9175

Publication date Collection: 2016

Publication date (Electronic): 16 March 2016

Volume: 5

Electronic Location Identifier: 38

Affiliations

[1]Isfahan Endocrinology and Metabolism Research Center, Isfahan, Iran

[1 ]Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

[2 ]Cardiovascular Research Laboratory, University of California, Los Angeles, CA, USA

Author notes

Address for correspondence: Dr. Noushin Khalili, Isfahan Endocrinology and Metabolism Research Center, Sedighe Tahere Care Center, Khorram Street, Isfahan, Iran. E-mail: n_khalili@ 123456med.mui.ac.ir

Article

Publisher ID: ABR-5-38

DOI: 10.4103/2277-9175.178783

PMC ID: 4815523

PubMed ID: 27099851

SO-VID: dbe5ad9d-4747-470f-a3fb-f742d2d6bd7f

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Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine

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Most cited references 22

Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study.

The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial.

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death.

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