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Left Ventricular Diastolic Dysfunction in Patients with Subclinical Hypothyroidism
Abstract
Although subclinical hypothyroidism is frequently diagnosed, the decision to institute a substitutive therapy with L-T4 remains controversial. Because the cardiovascular system is considered a main target for the action of thyroid hormone, we investigated whether subclinical hypothyroidism induces cardiovascular abnormalities. Twenty-six patients (mean age, 36 +/- 12 yr) were evaluated by Doppler-echocardiography, whereas a subgroup of 10 patients, randomly selected, were reevaluated after 6 months of L-T4 substitutive therapy (mean dose, 68 microg daily). Thirty subjects (matched for age, sex, and body surface area) served as controls. Mean plasma TSH was significantly higher in patients (P < 0.001), whereas mean serum free T4 and free T3 concentrations, although in the normal range, were significantly lower (P < 0.001 and P < 0.005, respectively). Blood pressure and heart rate did not differ from control values. Echocardiogram examination showed no abnormalities of the left ventricular morphology and a slight, but not significant, reduction in the systolic function in the patient group. In contrast, Doppler-derived indices of diastolic function showed significant prolongation of the isovolumic relaxation time (94 +/- 13 vs. 84 +/- 8 msec; P < 0.001), increased A wave (55 +/- 13 vs. 48 +/- 9 cm/sec; P < 0.05), and reduced early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.4 +/- 0.3 vs. 1.7 +/- 0.3; P < 0.001). In the subgroup of 10 patients, thyroid hormone profile was normalized by 6 months of L-T4 substitutive therapy, whereas no changes were observed in the left ventricular morphology. Systolic function was significantly enhanced, as compared with pretreatment values (P < 0.01) but did not differ from control values. Also, systemic vascular resistance was significantly decreased by L-T4 replacement therapy. Assessment of diastolic function showed significant shortening of isovolumic relaxation time (77 +/- 15 vs. 91 +/- 8; P < 0.05), reduction of A wave (51 +/- 13 vs. 60 +/- 12; P < 0.01), and increase of early diastolic mitral flow velocity/late diastolic mitral flow velocity ratio (1.7 +/- 0.4 vs. 1.3 +/- 0.3; P < 0.001). These indices, however, were comparable with those of control subjects. These findings indicate that subclinical hypothyroidism affects diastolic function and that this abnormality may be reversed by L-T4 substitutive therapy.
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“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 [88]
In the citing paper
“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 [91]
In the citing paper
“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 [91]
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Metadata
- Authors
- Biondi, B., Fazio, S., Palmieri, E. A., Carella, C., Panza, N., Cittadini, A., Bonè, F., Lombardi, G., & Saccà, L.
- Affiliations
- Federico II University Hospital (IT)
- Departments of Internal Medicine (S.F., E.A.P., A.C., F.B., L.S.), Naples, Italy
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-06-01
- Volume
- 84
- Issue
- 6
- Pages
- 2064-2067
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2096560123
- Cited by
- 334
- References
- 38
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 12 · 2021: 9 · 2020: 19 · 2019: 9 · 2018: 7 · 2017: 16 · 2016: 6 · 2015: 12 · 2014: 12 · 2013: 18 · 2012: 14
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- 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, left ventricular diastolic dysfunction, levothyroxine replacement therapy, thyroid hormones, isovolumic relaxation time, mitral inflow velocity, a-wave, systolic function, systemic vascular resistance, thyroid-stimulating hormone, Doppler echocardiography, young adults, thyroid autoimmunity, Graves' disease, Hashimoto's thyroiditis
- MeSH terms
- Adult, Female, Hemodynamics, Humans, Hypothyroidism, Male, Thyrotropin, Thyroxine, Echocardiography, Doppler, Ventricular Dysfunction, Left
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