The Thyroid Epidemiology, Audit, and Research Study (TEARS): Morbidity in Patients with Endogenous Subclinical Hyperthyroidism
Abstract
OBJECTIVE: Our objective was to investigate the long-term outcomes for patients with endogenous subclinical hyperthyroidism (SH). DESIGN: Population record-linkage technology was used retrospectively to identify patients with SH and hospital admissions from January 1, 1993, to December 31, 2009. PATIENTS: All Tayside residents over 18 yr old with at least two serum TSH measurements below the reference range for at least 4 months apart and normal free T(4)/total T(4) and normal total T(3) concentrations at baseline were included as potential cases. Using a unique patient identifier, data linkage enabled a cohort of SH cases to be identified from biochemistry, prescription, admission, and radioactive iodine treatment records matched to five comparators from the general population. OUTCOME MEASURES: The association between endogenous SH and cardiovascular disease, fracture, dysrhythmia, dementia, and cancer was assessed. RESULTS: Compared with the reference population, SH was associated with an increased risk of nonfatal cardiovascular morbidity, osteoporotic fracture, dysrhythmia, and dementia, with adjusted hazard ratios (HR) of 1.39 (1.22-1.58), 1.25 (1.04-1.50), 1.65 (1.26-2.17), and 1.64 (1.20-2.25), respectively. When SH patients who developed overt hyperthyroidism during follow-up were excluded, SH patients were associated with an increased risk of cardiovascular morbidity [HR = 1.36 (1.19-1.57)], dysrhythmia [HR = 1.39 (1.02-1.90)], and dementia [HR = 1.79 (1.28-2.51)] but not fracture and cancer. CONCLUSION: Patients with endogenous SH have an increased risk of cardiovascular disease and dysrhythmia. There is an association with fracture and dementia that is not related to TSH concentration and therefore is less likely to be causally related. No association was found between SH and cancer.
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In TEARS, SHyper was associated with an increased risk of fractures that was not related to TSH concentration.
“In TEARS, SHyper was associated with an increased risk of fractures that was not related to TSH concentration [63] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [63]
Conflicting results have been reported regarding the risk of fractures in SHyper.
“Conflicting results have also been reported regarding the risk of fractures [63,105,106] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [63]
In the Thyroid Epidemiology, Audit and Research Study, the risk of dementia, although increased in endogenous subclinical hyperthyroidism, was not related to TSH concentration, suggesting that it was not causally related.
“The risk of dementia, although increased in Endo SHyper, was not related to TSH concentration in the Thyroid Epidemiology, Audit and Research Study (TEARS), suggesting that it was not causally related [63] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [63]
In a large retrospective case-control study, an association between subclinical hyperthyroidism and increased risk of arrhythmia was reported in patients with grade 2 subclinical hyperthyroidism.
“Similarly, in a large retrospective case-control study, which was not included in the metaanalysis by Collet et al., an association between SHyper and increased risk of arrhythmia was reported in patients with grade 2 SHyper [63] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [63]
Some of these studies, including the meta-analyses, have also examined nonfatal cardiovascular events in SH, with similar increased risks.
“Some of these studies, including the meta-analyses, have also examined nonfatal cardiovascular events in SH, with similar increased risks (383,388,390,391).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [391]
A number of population-based studies have reported that certain groups of subjects with SH have increased fracture rates, including all adults, postmenopausal women, men, or subjects who progress to overt hyperthyroidism over time.
“A number of population-based studies have reported that certain groups of subjects with SH have increased fracture rates, including all adults (407), postmenopausal women (408), men (409), or subjects who progress to overt hyperthyroidism over time (391).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [391]
Subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH.
“Sawin et al. (399) first reported a 2.8-fold increased risk of atrial fibrillation in SH subjects over age 60 years in 1994, and subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH (381,384,388,391,400,401).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [391]
Subclinical hyperthyroidism is associated with increased cardiovascular events.
“Some of these studies re-ported increased risks of overall mortality in older subjects (380,429), cardiovascular events (391), heart failure (381), and atrial fibrillation in all subjects (401) or in older subjects (384), and vertebral fractures in older women (408).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [391]
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- Authors
- Vadiveloo, T., Donnan, P. T., Cochrane, L., & Leese, G. P.
- Affiliations
- University of Dundee (GB)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2011-05
- Volume
- 96
- Issue
- 5
- Pages
- 1344-1351
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2163166383
- Cited by
- 186
- References
- 20
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 14 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 12 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 19 · 2015: 11 · 2014: 10 · 2013: 12 · 2012: 21
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- GlaxoSmithKline
- 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, cardiovascular morbidity, cardiac arrhythmias, osteoporotic fractures, dementia, cancer risk, overt hyperthyroidism, thyroid-stimulating hormone, long-term outcomes, thyroid dysfunction
- MeSH terms
- Age Factors, Aged, Arrhythmias, Cardiac, Cardiovascular Diseases, Dementia, Female, Follow-Up Studies, Humans, Hyperthyroidism, Male, Middle Aged, Neoplasms, Osteoporosis, Scotland, Sex Factors, Thyroid Hormones, Thyrotropin, Databases, Factual, Treatment Outcome, Risk Assessment, Fractures, Bone
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