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High Frequency of and Factors Associated with Thyroid Hormone Over-Replacement and Under-Replacement in Men and Women Aged 65 and Over
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CONTEXT: Thyroid hormone use is common in older populations, but the frequency of over- or under-replacement is debated. OBJECTIVE: We sought to describe the frequency of and factors associated with thyroid hormone over- or under-replacement in a population of older men and women. DESIGN: Participants were 3678 U.S. community dwelling individuals aged 65 yr or older enrolled in the Cardiovascular Health Study who had thyroid function tests in 1989-1990. Thyroid hormone users (n = 339) were identified and classified into low TSH (<0.45 mU/liter), euthyroid (0.45-4.5 mU/liter), and high TSH (>4.5 mU/liter). RESULTS: Of the 339 thyroid hormone users, 41% had a low TSH, 16% had a high TSH, and 43% were in the euthyroid range. In multivariable analyses, lower weight (P < 0.001) was independently associated with low TSH status. For every 10 kg lower weight, the likelihood of having low TSH increased by 65% [odd ratio (OR) 1.65; 95% confidence interval (CI) 1.31-2.07]. Those with renal insufficiency were less likely to have low TSH levels (P = 0.02). The presence of diabetes was independently associated with having low (OR 3.35; 95% CI 1.46-7.65) and high TSH levels (OR 2.66; 95% CI 1.14-6.21). CONCLUSIONS: There is a very high prevalence of thyroid function testing abnormalities in older people taking thyroid hormone preparations, particularly in those of low weight or with diabetes. Because of potential adverse cardiovascular and skeletal effects from over-replacement, older people represent a key population for increased TSH monitoring on therapy.
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“nine studies over nearly 30 years across five different countries show that only 50% -70% of patients prescribed levothyroxine maintain serum TSH within reference range. 20,30 -34”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [33]
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“Levothyroxine has a narrow therapeutic index, however, and both under -treatment (TSH above the reference range) and over -treatment (TSH below the reference range) are common, with cross -sectional studies consistently showing that 30% -50% of patients on levothyroxine have TSH values outside of the laboratory reference range. 20,30 -34,65”
From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [33]
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“Among patients with hypothyroidism taking levothyroxine, studies 67-70 have reported a cumulative incidence of low thyrotropin levels in 5% to 41% and high thyrotropin levels in approximately 5% to 21%, with varying incidence depending on the population, clinical setting, and criteria used to define abnormal thyrotropin levels.”
From Hypothyroidism: A Review (2025) · cites this paper as [68]
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“This may be related to differences in body size and pharmacokinetics between the sexes.14 28 61”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [14]
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Metadata
- Authors
- Somwaru, L. L., Arnold, A. M., Joshi, N., Fried, L. P., & Cappola, A. R.
- Affiliations
- University of Pennsylvania (US)
- University of Washington (US)
- Columbia University (US)
- Corresponding author
- Cappola, Anne R.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-04-01
- Volume
- 94
- Issue
- 4
- Pages
- 1342-1345
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2682480
- OpenAlex
- W2161444360
- Cited by
- 239
- References
- 17
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 18 · 2023: 21 · 2022: 14 · 2021: 22 · 2020: 19 · 2019: 23 · 2018: 15 · 2017: 14 · 2016: 17 · 2015: 4 · 2014: 8 · 2013: 11 · 2012: 8
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- University of Pennsylvania
- National Institutes of Health (n01hc085079-024, n01hc015103-009, n01hc085086-022, n01hc035129-010)
- National Institute on Aging (K23AG19161, K23AG019161)
- National Heart, Lung, and Blood Institute (N01 HC085086, N01HC15103, N01 HC085079, N01 HC85086, N01 HC035129, N01 HC015103, N01-HC-85079 through N01-HC-85086, N01-HC85079, N01HC35129)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- thyroid hormone replacement, TSH levels, older adults, underweight, diabetes mellitus, renal failure, thyroid function tests, TSH monitoring, Cardiovascular Health Study
- MeSH terms
- Aged, Body Weight, Diabetes Mellitus, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Male, Risk Factors, Thyroid Diseases, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Body Mass Index, Multivariate Analysis, Hormone Replacement Therapy, Renal Insufficiency
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