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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.
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“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]
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“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]
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Raut, B., Paudel, N., & Bhosekar, N. (2020) · Journal of Diabetes and Endocrine Association of Nepal · doi:10.3126/jdean.v4i2.34589 · Cited by 3
Thyroid and Cardiovascular Risk
Waring, A. C., & Cappola, A. R. (2009) · Springer eBooks · doi:10.1007/978-88-470-1143-4_14 · Cited by 3
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Aging and Subclinical Thyroid Dysfunction
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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
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