Effect of Levothyroxine on Cardiac Function and Structure in Subclinical Hypothyroidism: A Double Blind, Placebo-Controlled Study
Open accessAbstract
Subclinical hypothyroidism (sHT) affects 5-15% of the general population; however, the need of lifelong L-T(4) therapy is still controversial. As myocardium is a main target of thyroid hormone action, we investigated whether sHT induces cardiovascular alterations. Twenty sHT patients were randomly assigned to receive placebo or L-T(4) therapy and were followed for 1 yr. Twenty sex- and age-matched normal subjects served as controls. Doppler echocardiography and videodensitometric analysis were performed in all subjects. Myocardium textural parameters were obtained as mean gray levels, which were then used to calculate the cyclic variation index (CVI; percent systolic/diastolic change in mean gray levels). Patients had a significantly higher isovolumic relaxation time (3.1 +/- 0.5 vs. 2.6 +/- 0.6; P < 0.03), peak A (0.77 +/- 0.16 vs. 0.56 +/- 0.13 m/s; P < 0.01), and preejection/ejection time (PEP/ET) ratio (0.72 +/- 0.05 vs. 0.57 +/- 0.06; P < 0.03) and a lower CVI (P < 0.0001) than controls. CVI was inversely related to TSH level (P < 0.0001) and PEP/ET ratio (P < 0.01). L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio (P < 0.05), peak A (P < 0.05), and isovolumic relaxation time (P < 0.05) along with a normalization of CVI. Conversely, no changes were observed in the placebo-treated group. In conclusion, sHT affects both myocardial structure and contractility. These alterations may be reversed by L-T(4) therapy.
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RCTs have demonstrated that LT4 replacement therapy affects myocardial function, particularly diastolic function, and over time the brachial artery intimal thickness.
“Similarly, RCTs have demonstrated that LT4 replacement therapy affects myocardial function (87) and particularly diastolic function (88-92), and, over time, the brachial artery intimal thickness (89,93).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [89]
Trials of levothyroxine in subclinical hypothyroidism using surrogate markers have shown improvement in left ventricular function, vascular endothelial function, atherogenic lipid particles, or cardiac mitochondrial function.
“Trials of levothyroxine in SCH using surrogate markers have shown improvement in LV function, vascular endothelial function, atherogenic lipid particles, or cardiac mitochondrial function (4,91,105-108).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [107]
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- Authors
- Monzani, F., Di Bello, V., Caraccio, N., Bertini, A., Giorgi, D., Giusti, C., & Ferrannini, E.
- Affiliations
- University of Pisa (IT)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2001-03
- Volume
- 86
- Issue
- 3
- Pages
- 1110-1115
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2123066698
- Cited by
- 308
- References
- 36
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 20 · 2019: 12 · 2018: 15 · 2017: 15 · 2016: 14 · 2015: 10 · 2014: 14 · 2013: 20 · 2012: 16
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, levothyroxine, thyroid hormone replacement, cardiac function, cardiac contractility, isovolumic relaxation time, myocardial texture, thyroid-stimulating hormone, Doppler echocardiography, videodensitometry
- MeSH terms
- Adult, Diastole, Double-Blind Method, Female, Heart, Humans, Hypothyroidism, Image Processing, Computer-Assisted, Male, Myocardium, Placebos, Systole, Thyrotropin, Thyroxine, Triiodothyronine, Videotape Recording, Echocardiography, Doppler
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