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A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

Taylor, Peter N., Razvi, Salman, Pearce, Simon H., Dayan, Colin M.·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2013-1315

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Abstract

CONTEXT: Overt thyroid disease is associated with profound adverse health outcomes; however, data are conflicting for studies of borderline/subclinical thyroid dysfunction. Many studies of subclinical thyroid disease have had low power and were prone to selection bias. In contrast, large datasets are available from community studies in healthy individuals. Studies of the effects of variation of thyroid function across the reference range on health outcomes in these populations may provide useful information regarding thresholds for treatment of abnormal thyroid function. EVIDENCE ACQUISITION: MEDLINE and the Cochrane Database of Systematic Reviews and Controlled Trials Register were searched for articles studying the effect of variation in thyroid hormone parameters within the reference range on cardiovascular, bone, metabolic, pregnancy, neurological, and psychological outcomes. EVIDENCE SYNTHESIS: Higher TSH/lower thyroid hormone levels are associated with more cardiovascular risk factors and cardiovascular events and worse metabolic parameters and pregnancy outcomes, whereas lower TSH/higher thyroid hormone levels are associated with reduced bone mineral density and increased fracture risk. The evidence base was good for cardiovascular, metabolic, bone, and pregnancy outcomes; however, high-quality data remained lacking for neurological and psychological outcomes. CONCLUSIONS: Common variation in persons with thyroid function in the normal range are associated with adverse health outcomes. These data suggest, by extrapolation, that carefully monitored treatment of even modest elevations of TSH may have substantial health benefits. Appropriately powered large-scale clinical trials analyzing the risks vs benefits of treating subclinical thyroid disease are required to determine whether these benefits can be achieved with levothyroxine therapy.

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Authors: Taylor, P. N., Razvi, S., Pearce, S. H., & Dayan, C. M.
Affiliations: Cardiff University (GB)
Gateshead Health NHS Foundation Trust (GB)
Royal Victoria Infirmary (GB)
Corresponding author: Dayan, Colin M.
ORCID: Taylor, Peter N.
Razvi, Salman
Pearce, Simon H.
Dayan, Colin M.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2013-09
Volume: 98
Issue: 9
Pages: 3562-3571
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2013-1315
OpenAlex: W2136343353
Cited by: 274
References: 101
Citations by year: 2026: 9 · 2025: 14 · 2024: 18 · 2023: 19 · 2022: 25 · 2021: 24 · 2020: 17 · 2019: 29 · 2018: 18 · 2017: 20 · 2016: 33 · 2015: 26 · 2014: 17 · 2013: 5
FWCI: 3.97
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Cardiff University
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 › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical thyroid dysfunction, thyroid-stimulating hormone, thyroid hormones, cardiovascular risk, bone mineral density, fracture risk, pregnancy outcomes, metabolic outcomes, levothyroxine therapy, treatment thresholds, healthy individuals
MeSH terms: Cardiovascular Diseases, Female, Humans, Male, Pregnancy, Pregnancy Outcome, Reference Values, Risk Factors, Thyroid Diseases, Thyroid Gland, Thyroid Hormones

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A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range

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