Thyroid Function in the Euthyroid Range and Adverse Outcomes in Older Adults
Open accessAbstract
CONTEXT: The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned. OBJECTIVE: This study aimed to determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS: US community-dwelling adults years of older (n = 2843) enrolled onto the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range. MAIN OUTCOME MEASURES: Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death were measured. RESULTS: No departures from linearity were detected. Higher TSH was negatively associated (P = .03) and higher FT4 was positively associated (P = .007) with mortality. Higher FT4 was associated with atrial fibrillation (P < .001) and heart failure (P = .004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (P < .05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure, and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all P < .05). Total T3 was not associated with any outcome. CONCLUSIONS: Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people.
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Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT4 levels and in patients with underlying heart disease.
“Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT 4 levels and in patients with underlying heart disease [71-73, 76, 77, 87, 91, 92, 94] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [94]
The Results (page unavailable) report higher rates of atrial fibrillation, coronary heart disease, heart failure, and all-cause mortality in older adults in the highest versus lowest FT4 quartile. They report no interaction with sex, so the paper does not support a particular increase in men. It also does not establish a greater increase in patients with underlying heart disease or specifically report increased cardiovascular mortality. (LLM, conf=0.90)
Experimental — accuracy not yet measuredLower TSH and higher FT4 concentrations were associated with an increased risk of multiple adverse events, including mortality, in older people.
“Recently, the Cardiovascular Health Study reported that lower TSH and higher FT 4 concentrations were associated with an increased risk of multiple adverse events, including mortality, in older people [94] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [94]
From a physiological standpoint, a continuum of effects may plausibly occur across the spectrum of normal TSH concentrations.
“from a physiological standpoint, a continuum of effects may plausibly occur across the spectrum of normal TSH concentrations9”
In older people, higher serum TSH and lower free T4 within the euthyroid range are associated with a lower risk of multiple adverse events, including mortality.
“recent evidence suggests that in older people, higher serum TSH and lower free T4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events including mortality.18”
From Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee (2016) · cites this paper as [18]
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- Authors
- Cappola, A. R., Arnold, A. M., Wulczyn, K., Carlson, M., Robbins, J., & Psaty, B. M.
- Affiliations
- Johns Hopkins University (US)
- University of Washington (US)
- University of Pennsylvania (US)
- University of California, Davis (US)
- Group Health Cooperative (US)
- Corresponding author
- Cappola, Anne R.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-03
- Volume
- 100
- Issue
- 3
- Pages
- 1088-1096
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4333030
- OpenAlex
- W2037507757
- Cited by
- 201
- References
- 42
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 19 · 2023: 15 · 2022: 22 · 2021: 20 · 2020: 19 · 2019: 19 · 2018: 14 · 2017: 18 · 2016: 23 · 2015: 13
- FWCI
- 14.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, n01hc085083-027, n01hc085080-026, n01hc085086-022, n01hc55222-0-0-0)
- National Institute on Aging (N01HC85081, N01HC85079, N01-HC-85080, N01-HC-85082, R56AG023629, R01AG032317, HHSN268200800007C, N01-HC-85083, AG023629, HL080295, K24AG042765, N01HC85083, N01HC85086, N01‐HC‐85086, R01AG023629, HHSN268201200036C)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01 HC085086, AG-023629, N01HC-85083, N01 HC085079, N01 HC085083, N01HC85082, N01 HC85086, N01 HC085080, HHSN 268200800007C, N01HC85080, N01 HC55222, HHSN268201200036C, N01HC085082, U01HL080295, N01 HC055222, N01 HC085081, HL080295, R01HL080295, N01-HC85079)
- National Institute of Neurological Disorders and Stroke (AG023629, HHSN268200800007C, N01-HC-85080, HL080295, N01-HC-85083, N01HC85082, N01-HC-85081, N01-HC-85086, N01 HC-55222, N01HC85079, HHSN268201200036C)
- 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 function, older adults, thyroid-stimulating hormone, free thyroxine, total T3, adverse outcomes, mortality, atrial fibrillation, coronary artery disease, heart failure, hip fracture, dementia, thyroid hormone replacement, reference values, Cardiovascular Health Study
- MeSH terms
- Aged, Aged, 80 and over, Aging, Atrial Fibrillation, Cause of Death, Coronary Disease, Dementia, Female, Heart Failure, Hip Fractures, Humans, Male, Prognosis, Reference Values, Thyroid Function Tests, Thyroid Gland, Incidence, Survival Analysis
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.
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