The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
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.
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
“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]
Citations
Cites
Teichholz, L. E., Kreulen, T. H., Herman, M. V., & Gorlin, R. (1976) · The American Journal of Cardiology · doi:10.1016/0002-9149(76)90491-4 · Cited by 2,568
Cardiac catheterization and angiography
(1975) · American Heart Journal · doi:10.1016/0002-8703(75)90525-6 · Cited by 455
Treatment Guidelines for Patients With Hyperthyroidism and Hypothyroidism
Singer, P. A. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520340064038 · Cited by 427 · cited 2×
“When the TSH level is less than 10 mU/L, the treatment may be indicated in relation to the presence of goiter or antithyroid antibodies to prevent the onset of overt hypothyroidism more than to tissue assessment of thyroid hormone deficiency (1).”
BackgroundL-Thyroxine Therapy in Subclinical Hypothyroidism: A Double-Blind, Placebo-Controlled Trial
COOPER, D. S., HALPERN, R., WOOD, L. C., LEVIN, A. A., & RIDGWAY, E. C. (1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-1-18 · Cited by 423
Diastolic Dysfunction in Congestive Heart Failure
Flier, J. S., Underhill, L. H., & Grossman, W. (1991) · New England Journal of Medicine · doi:10.1056/nejm199111283252206 · Cited by 346
Levothyroxine Therapy in Patients with Thyroid Disease
Mandel, S. J., Brent, G. A., & Larsen, P. R. (1993) · Annals of Internal Medicine · doi:10.7326/0003-4819-119-6-199309150-00009 · Cited by 324
Staub, J.-J., Althaus, B., Engler, H., Ryff, A., Trabucco, P., Marquardt, K., BURCKHARDT, D., Girard, J., & Weintraub, B. D. (1992) · The American Journal of Medicine · doi:10.1016/0002-9343(92)90782-7 · Cited by 317
Nyström, E., Caidahl, K., Fager, G., Wikkelsø, C., Lundberg, P. A., & Lindstedt, G. (1988) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1988.tb00250.x · Cited by 306
Screening for Thyroid Disease: An Update
Helfand, M., & Redfern, C. C. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-2-199807150-00020 · Cited by 304
Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine.
Biondi, B., Fazio, S., Carella, C., Amato, G., Cittadini, A., Lupoli, G., Saccà, L., Bellastella, A., & Lombardi, G. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.2.8345037 · Cited by 237
Self-citation
Flagged first, then by citations
1 of the 38 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 301–334 of 334
Miller, M. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-6231-8.10090-x
Znacaj dijagnostike poremecaja tireoidne funkcije - uticaj supklinickih poremecaja na bolesti srca
Djokić, O., Tomić, S., Petrovic, I. M., & Šarenac, D. (2012) · Medicinski glasnik Specijalna bolnica za bolesti stitaste zlezde i bolesti metabolizma Zlatibor · doi:10.5937/medgla1245021d
CLINICAL, METABOLIC, AND THYROID FUNCTION ORGAN-SPECIFIC INDICES OF
Klein, I. L. (2001)
Benozzi, S. F., Becerra, H., Bonacorsi, S. M., Marzialetti, M., Mo, S., & Flores-Fernández, C. (2012)
Year in review 2005: critical care--cardiology.
Gatheral, T. L., & Bennett, E. (2006) · Critical Care · doi:10.1186/cc4983
atualizacão Disfunções Mínimas da Tiróide: Hipotiroidismo Subclínico e Hipertiroidismo Subclínico
Romaldini, J. H., Sgarbi, J. A., & Farah, C. S. (2004)
Guías de práctica clínica para el tratamiento del hipotiroidismo
Brenta, G., Vaisman, M., Sgarbi, J. A., de Andrada, N. C., Bravo, P. P., Orlandi, A. M., & Graf, H. (2013)
Ferreira, M. M., Mansur, A. R., & Vaisman, M. (2010) · DOAJ (DOAJ: Directory of Open Access Journals)
EVALUATION OF CARDIAC INVOLVEMENT IN PATIENTS WITH PRIMARY HYPOTHYROIDISM
Kotha, S., Viraj, K., Rachita, V. G., & Jagadish, C. (2015) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/2015/1552
The Epidemiology and Management of Hypothyroidism in General Practice
Gibbons, V. (2011) · ResearchSpace (University of Auckland)
Clementino, U., Filho, F., Martins, R. M., Helena, R., Fonseca, A., Reuters, V. S., Ferreira, M. M., Almeida, C., Buescu, A., de Fátima, P., et al. (2011)
Maya, L. F. F., Clavijo, A. ́. G., Garcés, M. F., Pérez, M. T., Ruiz, A., Carreño-Dueñas, J. A., & Caminos, J. E. (2017) · Revista Colombiana de Endocrinología Diabetes & Metabolismo · doi:10.53853/encr.2.3.94
Rare and Unusual Forms of Hypertension
Grossman, E., & Messerli, F. H. (2007) · Elsevier eBooks · doi:10.1016/b978-1-4160-3053-9.50018-4
Biondi, B., & Kahaly, G. J. (2019) · Springer eBooks · doi:10.1007/978-3-319-72102-6_21
Self-citationThyroid Status and Outcomes in Kidney Disease
Rhee, C. M., Brent, G. A., & Kalantar‐Zadeh, K. (2019) · Springer eBooks · doi:10.1007/978-3-319-97765-2_8
Aspectos epidemiológicos das disfunções tiroidianas na população nipo-brasileira de Bauru
Sgarbi, J. A. (2011) · Americanae (AECID Library)
Novikov, E. V., & Потапенко, М. С. (2020) · Pathologia · doi:10.14739/2310-1237.2020.3.221774
Thyroid Function and Effects on Cardiovascular System
Berra, C., & Barrasso, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-80267-7_13
Ipotiroidismo subclinico: indicazioni al trattamento
Biondi, B., Pagano, L., Pulcrano, M., & Lombardi, G. (2005) · L Endocrinologo · doi:10.1007/bf03344510
Self-citation(2003) · Thyroid · doi:10.1089/105072503321087097
Sherif, A. H. E., El-Husseiny, R. M., Zaghla, H., Ahmed, A. F., & Youssef, M. S. I. (2022) · International Journal of Health Sciences · doi:10.53730/ijhs.v6ns1.5169
Mishra, S. K., & Gupta, A. (2022) · International Journal of Research in Medical Sciences · doi:10.18203/2320-6012.ijrms20221178
High Time to Consider the Role of Thyroid Function in Single Ventricle Heart Disease
Karahalios, D. S., & Sehgal, S. (2023) · Pediatric Cardiology · doi:10.1007/s00246-023-03201-1
Thyroid and Parathyroid Transplantation
Sakr, M. F. (2024) · Springer eBooks · doi:10.1007/978-3-031-64102-2_18
Massive Exudative Pleural Effusion With Hypothyroidism: A Case Report
Uehara, Y., Ogawa, N., Yamoto, T., Watanabe, N., & Kanasaki, K. (2025) · Cureus · doi:10.7759/cureus.80683
Thyroid Dysfunction, Metabolic Syndrome, and Cardiovascular Risk
Massarini, S., & Luzi, L. (2025) · Springer eBooks · doi:10.1007/978-3-032-01700-0_1
Saima Masood, A. Y. (2016) · International Journal of Biosciences (IJB) · doi:10.12692/ijb/9.4.305-314
Xie, Y., Chen, B., Gao, S., Li, J., Chen, B., & Han, J. (2026) · Biomedicines · doi:10.3390/biomedicines14061322
Arcopinto, M., Salerno, M., Mase, R. D., Salzano, A., Rotondo, F. R., Vasaturo, S., Cittadini, A., & Capalbo, D. (2026) · Journal of Endocrinological Investigation · doi:10.1007/s40618-026-03002-2
Self-citationLin, Y.-H., Hsu, C.-W., Liu, P., Huang, Y.-Y., & Lin, C.-H. (2026) · Endocrine · doi:10.1007/s12020-026-04651-2
Cardiac Morphology and Function in Mild Hypothyroidism
Biondi, B. (2009) · Springer eBooks · doi:10.1007/978-88-470-1143-4_3
Self-citationHypothyroidism and the Development of Hypertension
Short, K. F. (2015) · Cornerstone (Minnesota State University, Mankato)
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
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
