The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.
Thyroid hormone replacement for subclinical hypothyroidism
Open accessAbstract
BACKGROUND: Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormones values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general population, and up to 15% to 18% in women who are over 60 years of age. There is considerable controversy regarding the morbidity, the clinical significance of subclinical hypothyroidism and if these patients should be treated. OBJECTIVES: To assess the effects of thyroid hormone replacement for subclinical hypothyroidism. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. Ongoing trials databases, reference lists and abstracts of congresses were scrutinized as well. SELECTION CRITERIA: All studies had to be randomised controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for missing or additional information. MAIN RESULTS: Twelve trials of six to 14 months duration involving 350 people were included. Eleven trials investigated levothyroxine replacement with placebo, one study compared levothyroxine replacement with no treatment. We did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids, there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time as well as diastolic dysfunction. Only four studies reported adverse events with no statistically significant differences between groups. AUTHORS' CONCLUSIONS: In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“A meta-analysis related to a limited number of RCTs has shown how LT4 therapy, when compared to placebo, in subjects with SC-HT, could be associated with an improvement in lipid, glycaemia and some echocardiographic parameters, such as myocardial relaxation and diastolic function [31].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [31]
In the citing paper
“The drug levothyroxine (LT4) constitutes a safe, effective hormone replacement therapy for hypothyroidism caused by autoimmune thyroiditis, partial or total thyroidectomy, radioiodine treatment, or drug side effects [ 1 – 5 ].”
From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139
Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J., & McQuay, H. J. (1996) · Controlled Clinical Trials · doi:10.1016/0197-2456(95)00134-4 · Cited by 17,582
Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609
Statistical Methods for Rates and Proportions.
Everitt, B. S., & Fleiss, J. L. (1981) · Biometrics · doi:10.2307/2530193 · Cited by 9,034
Schulz (1995) · doi:10.1001/jama.1995.03520290060030 · Cited by 5,634
Dong, Y., Hao, L., Shi, Z., Wang, G., Zhang, Z., & Han, C. (2013) · Urologia Internationalis · doi:10.1159/000351405 · Cited by 4,557
Moher, D., Pham, B., Jones, A., Cook, D. J., Jadad, A. R., Moher, M., Tugwell, P., & Klassen, T. P. (1998) · The Lancet · doi:10.1016/s0140-6736(98)01085-x · Cited by 3,560
The Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
THE SPECTRUM OF THYROID DISEASE IN A COMMUNITY: THE WHICKHAM SURVEY
Tunbridge, W. M. G., Evered, D. C., Hall, R., Appleton, D. R., BREWIS, M., CLARK, F., Evans, J. G., Young, E. T., Bird, T., & Smith, P. (1977) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1977.tb01340.x · Cited by 2,665
Flagged first, then by citations
Research works printed but not linked: 2
- Higgins JPT Green S Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005] In: The Cochrane Library, Issue 3, 2005. Chichester, UK: John Wiley & Sons, Ltd
- Niström, 1988, A double-blind cross-over 12-month study of l-thyroxine treatment of women with "subclinical" hypothyroidism, Clinical Endocrinology(Oxf), 29, 63, 10.1111/j.1365-2265.1988.tb00250.x · DOI
Cited by
Sorted by citations
Items 301–330 of 330
Wellness and Whole-Person Care
Hutchinson, T. A., & Hutchinson, N. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.049
Herrera, N., & IsHak, W. W. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.040
Wellness in Cancer and Neoplastic Diseases
Bashmi, L., & IsHak, W. W. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.018
Wellness Interventions for Physicians and Healthcare Professionals
Goldenberg, M., & Danovitch, I. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.021
Neurological and Neurosurgical Disorders and Wellness
Ding, K., & Yang, I. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.007
Gastrointestinal System and Wellness
Robbins, L., & Feldman, E. J. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.009
Subclinical hypothyroidism in community perspective: Treat or not to treat?
Kant, R., Barnwal, S., Yadav, P., Tendulkar, P., & Bairwa, M. C. (2021) · Journal of Preventive Medicine and Holistic Health · doi:10.18231/j.jpmhh.2021.005
Hypothyroidism - A Causal Approach to Testing Assumptions against Empirical Results.
Glavin, R., Ness, R. O., & Nguyen, A. (2021) · PubMed
IsHak, W. W. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.051
Garla, V. V., Cardozo, L. L. Y., & Lien, L. F. (2018) · Springer eBooks · doi:10.1007/978-3-319-99079-8_2
Lundy, J. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.022
IsHak, W. W., Mann, A., Manoukian, V., Pakhdikian, S., Chaudhry, M., Liu, A., & Bart, R. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.001 · Cited by 2
Evaluation of L-thyroxine therapy in obese children with subclinical hypothyroidism – a pilot study
Januszek-Trzciąkowska, A., Matusik, P., & Klimek, K. (2013) · Pediatric Endocrinology · doi:10.18544/ep-01.12.02.1446
(2014) · Journal of Primary Health Care · doi:10.1071/hc14162a
IsHak, W. W. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108650182.053
Martins, C. D. S. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2022.tde-09052022-093801
Pradeep, B. J., Baghel, M., Sharma, B., & Modala, S. (2022) · International Journal of Health Sciences · doi:10.53730/ijhs.v6ns1.7780
Comorbidities associated with depression
Bondric‐Popescu, E.-C., & Cozman, D. (2022) · Psihiatru ro · doi:10.26416/psih.68.1.2022.6308
PECULIARITIES OF THE COURSE OF CARDIOVASCULAR PATHOLOGY IN SUBCLINICAL HYPOTHYROIDISM
Kuznetsova, O. E., Kruzhalin, E. E., Кутелев, Г. Г., Cherkashin, D. V., & Nikashin, A. N. (2023) · Translational Medicine · doi:10.18705/2311-4495-2023-10-3-209-222
Monika, K., Banait, S., Salunkhe, P., & Jain, J. (2021) · Journal of Datta Meghe Institute of Medical Sciences University · doi:10.4103/jdmimsu.jdmimsu_260_20
L-Thyroxin bei Hypothyreose – absetzen oder nicht?
Kramer, M. R., Bleckwenn, M., Deutsch, T., Voigt, K., & Schübel, J. (2024) · Zeitschrift für Allgemeinmedizin · doi:10.1007/s44266-024-00291-9
Hypothyreose - Hausärztliche Diagnostik und Therapie
Schübel, J. (2025) · CME · doi:10.1007/s11298-025-4258-8
Individualized homoeopathic treatment in subclinical hypothyroidism: A case report
Bhavana, P., & Akareddy, A. M. (2025) · International Journal of Homoeopathic Sciences · doi:10.33545/26164485.2025.v9.i3.n.1757
Cosmo, C. D., Pignata, L., Bagattini, B., Agretti, P., Marco, G. D., Ferrarini, E., Santini, F., Montanelli, L., & Tonacchera, M. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02718-x
Орлик, О. С. (2026) · Український медичний часопис · doi:10.32471/umj.1680-3051.273711
Omoteso, O., Sibanda, U., Zhou, A.-A., Melamane, S., Sibiya, N. H., Ndzamba, B., & Egunlusi, A. (2026) · SA pharmaceutical journal. · doi:10.36303/sapj.4384
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
Elagib, M. A. H., Alamin, M. A., Ahmed, Y. O. A., Musa, I. E. M., Khaleifa, M. A., Elsamani, E. A. E. M., Najar, H., & Ahmed, A. (2026) · Cureus · doi:10.7759/cureus.114468
França, M. M. (2013) · Americanae (AECID Library)
Riesgo vascular en enfermedades endocrinológicas distintas a la diabetes
Martín-Portugués, I. A., Cuende, J. I., López-Guerrero, J. N., & Valdivielso, P. (2015) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2015.05.001
Metadata
- Authors
- Villar, H. C. C. E., Saconato, H., Valente, O., & Atallah, Á. N.
- Affiliations
- Faculdade de Medicina de Marília (BR)
- Universidade Federal do Rio Grande do Norte (BR)
- Universidade Federal de São Paulo (BR)
- Cochrane (BR)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2007-07-18
- Volume
- 2009
- Issue
- 1
- Pages
- CD003419-CD003419
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6610974
- OpenAlex
- W1755700101
- Cited by
- 329
- References
- 82
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 74 · 2019: 13 · 2018: 23 · 2017: 24 · 2016: 12 · 2015: 22 · 2014: 19 · 2013: 23 · 2012: 16
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, levothyroxine, thyroid hormone replacement, thyroid-stimulating hormone, cardiovascular morbidity, cardiovascular mortality, health-related quality of life, cognitive function, serum lipids, left ventricular function, diastolic dysfunction, adverse events
- MeSH terms
- Adult, Cardiovascular System, Cholesterol, Humans, Hypothyroidism, Thyroxine, Randomized Controlled Trials as Topic, Hormone Replacement Therapy
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
