Effect of Levothyroxine Replacement on Lipid Profile and Intima-Media Thickness in Subclinical Hypothyroidism: A Double-Blind, Placebo- Controlled Study
Abstract
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-T(4) 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 (r(2) = 0.71, P < 0.0001) to age, TSH, and LDL cholesterol. L-T(4) 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-T(4) 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.
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Results of RCTs have indicated that cholesterol and SHBG levels are particularly affected by the administration of LT4.
“The results of RCTs have indicated that cholesterol (50,82-86), and SHBG levels (50) are particularly affected by the administration of LT4.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [83]
The most frequent cardiac abnormality observed in subclinical hypothyroidism is diastolic dysfunction due to impaired ventricular filling and relaxation.
“The most frequent cardiac abnormality observed in SCH is diastolic dysfunction due to impaired ventricular filling and relaxation (90,91).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [90]
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- Authors
- Monzani, F., Caraccio, N., Kozàkowà, M., Dardano, A., Vittone, F., Virdis, A., Taddei, S., Palombo, C., & Ferrannini, E.
- Affiliations
- University of Pisa (IT)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-05
- Volume
- 89
- Issue
- 5
- Pages
- 2099-2106
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2068309857
- Cited by
- 399
- References
- 48
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 17 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 24 · 2019: 17 · 2018: 30 · 2017: 28 · 2016: 21 · 2015: 15 · 2014: 27 · 2013: 29 · 2012: 20
- FWCI
- 13.23
- 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 › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, levothyroxine replacement, lipid profile, LDL cholesterol, apolipoprotein B, intima-media thickness, carotid artery, dyslipidemia, atherosclerosis, thyroid-stimulating hormone, cardiovascular risk
- MeSH terms
- Adult, Cholesterol, Double-Blind Method, Female, Humans, Hypothyroidism, Lipids, Cholesterol, LDL, Male, Middle Aged, Placebos, Regression Analysis, Thyrotropin, Thyroxine, Ultrasonography, Tunica Intima, Tunica Media
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