Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism

Surks, Martin I.; Hollowell, Joseph G.

doi:10.1210/jc.2007-1499

Cited by 750Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism

Surks, Martin I., Hollowell, Joseph G.·2007·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2007-1499

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Abstract

CONTEXT: Measurements from all age groups defined the upper limit of the TSH reference range in National Health and Nutrition Examination Survey III. The TSH median, 97.5 centile and prevalence of subclinical hypothyroidism (SCH), normal serum T(4) and TSH greater than 4.5 mIU/liter, increased progressively with age. Age-adjusted reference ranges would include many people with TSH greater than 4.5 mIU/liter. OBJECTIVE: We determined whether increasing 50 and 97.5 centiles with age resulted from more patients with SCH in populations with normal TSH distribution or whether age-specific population shifts to higher serum TSH might account for these findings. DESIGN/SETTING/PATIENTS: We analyzed TSH, antithyroid antibodies, and TSH frequency distribution curves for specific age deciles in populations without thyroid disease, with or without antithyroid antibodies. RESULTS: Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter, increasing to 40% in the 80+ group, 14.5% of whom had TSH greater than 4.5 mIU/liter. When TSH was greater than 4.5 mIU/liter, the percentage with antibodies was 67.4% (age 40-49 yr) and progressively decreased to 40.5% in the 80+ group. TSH frequency distribution curves of the 80+ group with or without antibodies was displaced to higher TSH, including TSH at peak frequency. The 97.5 centiles for the 20-29 and 80+ groups were 3.56 and 7.49 mIU/liter, respectively. Seventy percent of older patients with TSH greater than 4.5 mIU/liter were within their age-specific reference range. CONCLUSION: TSH distribution progressively shifts toward higher concentrations with age. The prevalence of SCH may be significantly overestimated unless an age-specific range for TSH is used.

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Higher serum TSH values might occur naturally as part of the ageing process.
“Although higher serum TSH values might occur naturally, as part of the ageing process, [15][16][17]”
From Hypothyroidism (2024) · cites this paper as [16]
There is robust evidence that serum TSH levels increase slightly with age, particularly after age 65-70 years.
“There is robust evidence that serum TSH levels increase slightly with age, particularly after the age of 65–70 years (9, 74).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [74]
In a population study, 70% of patients older than 80 years showed a serum TSH greater than 4.5 mU/L (97.5 centiles = 7.49 mU/L).
“In a population study, 70% of patients >80-years-old showed a serum TSH greater than 4.5 mU/L (97.5 centiles = 7.49 mU/L) (74).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [74]
NHANES III reported that the 97.5th percentile for TSH exceeded 7.0 mIU/L in individuals older than 80 years, even after exclusion of TPO-Ab-positive individuals.
“NHANES III reported the 97•5th percentile for TSH exceeded 7•0 mIU/L in individuals older than 80 years, 15,16 even after exclusion of TPO-Ab-positive individuals”
From Hypothyroidism (2024) · cites this paper as [16]
The shift in the normal TSH distribution to a higher range in older individuals might represent a normal part of ageing.
“This shift in the normal TSH distribution to a higher range in older individuals might represent a normal part of ageing,15-17,131”
From Hypothyroidism (2024) · cites this paper as [16]

The higher TSH in the elderly is not explained only by higher prevalence of thyroid autoimmunity.
“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 [37]
When age-specific reference ranges were employed in NHANES III, 70% of the >80 years group was reclassified as having normal for their age TSH rather than high TSH based on the general population reference range (>4.5 mU/l).
“When age-specific reference ranges were employed in the NHANES III study, 70% of the >80 yo group was reclassified as having normal for their age TSH rather than high TSH based on the reference range of the general population (>4.5 mU/l) (31).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [31]
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 [16]
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 [16]
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 [16]
Analysis of the NHANES data estimated that 70% of older patients with TSH above the laboratory reference interval had values within their age-specific reference brackets.
“Analysis of the NHANES data estimated that 70% of older patients with TSH above the laboratory reference interval had values within their age-specific reference brackets [16].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [16]
TPO antibody positivity is unlikely to be the sole explanation for higher TSH levels in the elderly, as the NHANES study identified that only 40% of the elderly with a TSH above 4.5 mU/L were TPO antibody positive.
“TPO antibody positivity is unlikely to tbe the sole explanation for higher TSH levels in the elderly as the NHANES study identified that only 40% of the elderly with a TSH above 4.5 mU/L were TPO antibody positive [16]”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [16]
In TRUST, the mean baseline TSH in both groups was below the age expected 97.5th percentile (normal) of euthyroid, antibody negative individuals observed for the US population.
“The mean baseline TSH in both groups was below the age expected 97.5 th percentile (normal) of euthyroid, antibody negative individuals observed for the US population”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [128]

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Authors: Surks, M. I., & Hollowell, J. G.
Affiliations: Albert Einstein College of Medicine (US)
University of Kansas Medical Center (US)
Corresponding author: Surks, Martin I.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2007-12
Volume: 92
Issue: 12
Pages: 4575-4582
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2007-1499
OpenAlex: W2033555047
Cited by: 750
References: 25
Citations by year: 2026: 23 · 2025: 20 · 2024: 29 · 2023: 64 · 2022: 66 · 2021: 46 · 2020: 47 · 2019: 48 · 2018: 48 · 2017: 44 · 2016: 52 · 2015: 30 · 2014: 37 · 2013: 52 · 2012: 45
FWCI: 17.78
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
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 hypothyroidism, serum thyrotropin, age-specific reference ranges, thyroid autoantibodies, older adults
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Aging, Autoantibodies, Child, Data Interpretation, Statistical, Female, Humans, Hypothyroidism, Iodide Peroxidase, Male, Middle Aged, Reference Values, Thyrotropin, Thyroxine, United States

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Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism

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