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Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study

Parle, James V, Maisonneuve, Patrick, Sheppard, Michael C, Boyle, Peter, Franklyn, Jayne A·2001·The Lancet
DOI 10.1016/s0140-6736(01)06067-6
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Abstract

Background Low serum thyrotropin, in combination with normal concentrations of circulating thyroid hormones, is common, especially in elderly people and in individuals with a history of thyroid disease. We aimed to assess the long-term effects of subclinical hyperthyroidism on mortality.Methods We did a population-based study of mortality in a cohort of 1191 individuals not on thyroxine or antithyroid medication. All participants were aged 60 years or older. We measured concentration of thyrotropin in serum at baseline in 1988-89. We recorded vital status on June 1, 1999, and ascertained causes of death for those who had died. We compared data for causes of death with age-specific, sex-specific, and year-specific data for England and Wales. We also compared mortality within the cohort according to initial thyrotropin measurement.Results During 9733 person-years of follow-up, 509 of 1191 people died, the expected number of deaths being 496 (standardised mortality ratio [SMR] 1.0, 95% CI 0.9-1.1). Mortality from all causes was significantly increased at 2 (SMR 2.1), 3 (2.1), 4 (1.7), and 5 (1.8) years after first measurement in those with low serum thyrotropin (n471). These increases were largely accounted for by significant increases in mortality due to circulatory diseases (SMR 2.1, 2.2, 1.9, 2.0, at years 2, 3, 4, and 5 respectively). Increases in mortality from all causes in years 2-5 were higher in patients with low serum thyrotropin than in the rest of the cohort (hazard ratios for years 2, 3, 4, and 5 were 2.1, 2.2, 1.8, and 1.8, respectively). This result reflects an increase in mortality from circulatory diseases (hazard ratios at years 2, 3, 4, and 5 were 2.3, 2.6, 2.3, 2.3), and specifically from cardiovascular diseases (hazard ratios at years 2, 3, 4, and 5 were 3.3, 3.0, 2.3, 2.2).Interpretation A single measurement of low serum thyrotropin in individuals aged 60 years or older is associated with increased mortality from all causes, and in particular mortality due to circulatory and cardiovascular diseases.

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  • Two studies included in a systematic review reported an increased risk of stroke in subclinical hyperthyroidism, and one study reported a statistically significant adjusted hazard ratio of 3.39 (95% CI 1.15-10.00).

    “Two studies included in this systematic review [79,81] reported an increased risk of stroke in SHyper, and one study reported a statistically significant adjusted HR (3.39; 95% CI: 1.15-10.00)[79] .”

    From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [81]

  • Suppressed TSH has in population studies consistently been associated with higher mortality and other adverse effects compared to people with normal or even higher TSH concentrations.

    “Thus, suppressed TSH has in population studies consistently been associated with a higher mortality and other adverse effects compared to people with normal or even higher TSH concentrations ( Table 5 ) (87–90).”

    From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [89]

  • The association between subclinical hypothyroidism and cardiovascular disease or mortality has not been confirmed in all studies.

    “However, this relationship has not been confirmed in all studies (94,99,100).”

    From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [100]

  • The findings of an association between elevated serum TSH and adverse cardiac outcomes have not been reproduced by all studies.

    “these findings have not been reproduced by all studies (13, 17, 25, 26)”

    From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [17]

  • A low serum TSH concentration is associated with a higher rate of cardiovascular events, osteoporotic fracture, dementia, and death.

    “Similarly, longitudinal studies have shown that a low serum TSH concentration is associated with a higher rate of cardiovascular events, osteoporotic fracture, dementia, and death (14, 17–20).”

    From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [17]

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Authors
Parle, J. V., Maisonneuve, P., Sheppard, M. C., Boyle, P., & Franklyn, J. A.
Affiliations
  • European Institute of Oncology (IT)
  • University of Birmingham (GB)
Corresponding author
Franklyn, Jayne A
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2001-09
Volume
358
Issue
9285
Pages
861-865
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(01)06067-6
OpenAlex
W2100106207
Cited by
669
References
18
Citations by year
2026: 1 · 2025: 5 · 2024: 10 · 2023: 12 · 2022: 13 · 2021: 13 · 2020: 14 · 2019: 17 · 2018: 19 · 2017: 25 · 2016: 25 · 2015: 23 · 2014: 34 · 2013: 35 · 2012: 49
FWCI
21.01
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
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 hyperthyroidism, thyroid-stimulating hormone, cardiovascular mortality, all-cause mortality, older adults, circulatory diseases, mortality prediction, thyroid function, long-term prognosis, antithyroid drugs, thyroxine therapy, cardiovascular risk factors, alcohol consumption, physical activity, body mass index, blood pressure, cholesterol
MeSH terms
Aged, Cardiovascular Diseases, Cause of Death, Female, United Kingdom, Humans, Male, Middle Aged, Thyrotropin, Cohort Studies, Survival Analysis, Age Distribution, Sex Distribution

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