Age- and Gender-Specific TSH Reference Intervals in People With No Obvious Thyroid Disease in Tayside, Scotland: The Thyroid Epidemiology, Audit, and Research Study (TEARS)

Vadiveloo, Thenmalar; Donnan, Peter T.; Murphy, Michael J.; Leese, Graham P.

doi:10.1210/jc.2012-3191

Cited by 204Thyroid Disorders and TreatmentsClinical Laboratory Practices and Quality ControlThyroid Cancer Diagnosis and Treatment

Age- and Gender-Specific TSH Reference Intervals in People With No Obvious Thyroid Disease in Tayside, Scotland: The Thyroid Epidemiology, Audit, and Research Study (TEARS)

Vadiveloo, Thenmalar, Donnan, Peter T., Murphy, Michael J., Leese, Graham P.·2013·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2012-3191

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Abstract

OBJECTIVE: The aim of the study was to examine the association of tested TSH with age, gender, and diabetes in a large population-based cohort without evidence of thyroid disease. DESIGN: Record-linkage technology was used retrospectively to identify people without evidence of thyroid disease in the general population of Tayside, Scotland, from July 1, 2003, to December 31, 2009. COHORT: All Tayside residents who had thyroid function tests performed were identified. Using a unique patient identifier, data linkage enabled a cohort without thyroid disease to be identified by excluding anyone with thyroid or antithyroid prescription, thyroid-related admission or surgery, treatment with radioactive iodine and/or positive thyroid antibodies. Cases below 18 years of age were also excluded. OUTCOME MEASURES: We measured TSH distribution among different age groups and by gender. RESULTS: We identified the latest TSH measurements in 153127 people from the reference population after applying the exclusion criteria. There was a significant increase in median TSH (1.58 mU/L at 31-40 y to 1.86 mU/L at >90 y; P < .001) and 97.5th centile TSH (3.98 to 5.94 mU/L, respectively) with increasing age. The 2.5th centile decreased with age (0.51 to 0.31 mU/L). Patients with diabetes had marginally higher TSH concentration (1.80 vs 1.70 mU/L; P < .001). CONCLUSION: The use of these age-specific reference intervals for TSH, especially in those over 70 years old, would result in the reclassification of many TSH results from "abnormal" to "normal" (within the 95th centile reference interval) and avoid unnecessary treatment.

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The 97.5th percentiles of the reference population are considerably higher in the elderly (older than 70 years old) than in younger adults.
“The 97.5th percentiles of the reference population are considerably higher in the elderly (older than 70 years old) than in younger adults [32–35], which is not explained only by higher prevalence of thyroid autoimmunity [36, 37].”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [33]
Studies in several populations have shown progressively increasing TSH concentrations with age.
“Studies in several populations (Americans, Scottish, Ashkenazi Jews, Chinese) have shown progressively increasing TSH concentrations with age.”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [33]
The normal TSH distribution curve is shifted to the right in the elderly.
“the normal TSH distribution curve is shifted to the right in the elderly (Fig. 1) and it is increasingly recognised that higher TSH levels may represent a normal part of ageing [15–17].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [17]
TSH concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations.
“Thyroid stimulating hormone (TSH) concentrations are higher at the extremes of life and show a U-shaped longitudinal trend in iodine sufficient Caucasian populations.”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [17]
Higher TSH levels may represent a normal part of ageing.
“it is increasingly recognised that higher TSH levels may represent a normal part of ageing [15–17].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [17]

These studies show that the reference range becomes wider as age increases, with lower 2.5 centiles in the older age groups.
“These studies also show that the reference range becomes wider as age increases, with lower 2.5 centiles in the older age groups (Fig. 3).”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [17]
Several large cross-sectional studies in iodine-replete thyroid disease-free populations have reported higher TSH concentrations in older individuals.
“Several large cross-sectional studies in iodine-replete thyroid disease-free populations have reported higher TSH concentrations in older individuals (Fig. 3), [15, 17, 87, 88].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [17]
Reference ranges may be device-, laboratory-, and population-specific, and normal or abnormal results may be diagnosed using reference ranges from populations local to the laboratory.
“Reference ranges may be device-, laboratory-, and population-specific, and “normal” or “abnormal” results may be diagnosed using reference ranges from populations local to the laboratory [20].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [20]
Higher levels of TSH are observed in women than in men.
“Increasing TSH with age was observed for both men and women in this study, while this and other studies have demonstrated higher levels of TSH in women than in men [14, 20, 23, 24].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [20]
In a population of about 150,000 thyroid antibody-negative people without history of treatment for a thyroid-related condition, the 97.5th percentile for TSH increased from 3.98 mIU/L at age 31-40 to 5.94 mIU/L at age >90 years.
“A study in a population of about 150,000 thyroid antibody-negative people, without the history of treatment for a thyroid-related condition, found that the 97.5th percentile for TSH (i.e., the upper limit for a TSH reference range in this population) increased from 3.98 mIU/L at age 31–40 to 5.94 mIU/L at age >90 years [20].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [20]
A multitude of physiological and pathophysiological influences modulates the relationship between TSH and thyroid hormones at various sites of action, thereby influencing the location of the set point in health and disease.
“Furthermore, a multitude of physiological and pathophysiological influences modulates the relationship between TSH and thyroid hormones at various sites of action, thereby influencing the location of the set point in health and disease (Table 2) (8, 9, 76, 91–111).”
From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [92]

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Authors: Vadiveloo, T., Donnan, P. T., Murphy, M. J., & Leese, G. P.
Affiliations: University of Dundee (GB)
Corresponding author: Vadiveloo, Thenmalar
ORCID: Vadiveloo, Thenmalar
Donnan, Peter T.
Murphy, Michael J.
Leese, Graham P.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2013-03-01
Volume: 98
Issue: 3
Pages: 1147-1153
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2012-3191
OpenAlex: W2020249822
Cited by: 204
References: 19
Citations by year: 2026: 9 · 2025: 15 · 2024: 12 · 2023: 18 · 2022: 16 · 2021: 14 · 2020: 19 · 2019: 24 · 2018: 20 · 2017: 17 · 2016: 13 · 2015: 10 · 2014: 10 · 2013: 7
FWCI: 10.45
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)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: thyroid-stimulating hormone, TSH reference intervals, age-related reference values, sex differences, diabetes mellitus, thyroid function tests, thyroid dysfunction, older adults, Tayside
MeSH terms: Adult, Aged, Aged, 80 and over, Autoantibodies, Diabetes Mellitus, Female, Humans, Male, Medical Audit, Middle Aged, Morbidity, Reference Values, Retrospective Studies, Scotland, Thyroid Diseases, Thyroid Gland, Glycoprotein Hormones, alpha Subunit, Seroepidemiologic Studies, Databases, Factual, Age Distribution, Sex Distribution, Thyrotropin, beta Subunit

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Age- and Gender-Specific TSH Reference Intervals in People With No Obvious Thyroid Disease in Tayside, Scotland: The Thyroid Epidemiology, Audit, and Research Study (TEARS)

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