Age- and Race-Based Serum Thyrotropin Reference Limits
Abstract
CONTEXT: TSH reference limits, particularly the upper limit, are controversial. The traditional and prevailing method for setting limits uses TSH distribution of thyroid disease-free individuals. The curve is not Gaussian, but skewed to higher concentrations, even after log-transformation; values in the skewed area are assumed to reflect mild hypothyroidism. The underlying assumption for this traditional approach, which has not previously been tested, is that the limits derived from this curve are applicable to all people. However, recent studies suggest that distinct subpopulations have unique TSH distribution and reference limits that are significantly different from limits established by the traditional approach. EVIDENCE ACQUISITION: A search was focused on articles that provide the basis for current recommendations for setting TSH reference limits as well as articles that suggest that the traditional method does not reflect accurately the TSH distribution and reference limits of distinct subpopulations within the United States. EVIDENCE SYNTHESIS: TSH distribution and reference limits shift to higher concentrations with age, even up to centenarians, and are unique for different racial/ethnic groups, being at higher concentrations in Caucasians than either Blacks or Hispanics originating from Puerto Rico or the Dominican Republic. The distribution curve derived by the traditional approach represents a composite of curves from specific subpopulations that do not provide appropriate reference limits for those unique groups. CONCLUSIONS: Age- and race-specific TSH distribution and reference limits, possibly influenced by genetic factors, should be employed to provide clinicians accurate limits for specific populations and guidance for further evaluation of thyroid dysfunction.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Large population studies have demonstrated a shift in the TSH level towards higher concentrations with advanced age in healthy individuals in iodine-replete areas.
“Large population studies have demonstrated a shift in the TSH level towards higher concentrations with advanced age in healthy individuals in iodine-replete areas [22] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [22]
TSH concentrations in healthy individuals oscillate around a narrow point, which is strongly influenced by their genetic architecture.
“TSH concentrations in healthy individuals oscillate around a narrow point, 18 which is strongly influenced by their genetic architecture.19,20”
From Hypothyroidism (2024) · cites this paper as [20]
Studies in iodine-replete populations without thyroid disease have reported higher TSH concentrations in older individuals.
“studies in iodine-replete populations without thyroid disease have reported higher TSH concentrations in older individuals.15,17,19,20”
From Hypothyroidism (2024) · cites this paper as [20]
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 [87]
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 [87]
NHANES III reported an age-related increase in TSH with the 97.5 centile exceeding 7.0 mIU/L in individuals aged over 80 years.
“The National Health and Nutrition Examination Survey (NHANES) III reported an age-related increase in TSH with the 97.5 centile exceeding 7.0 mIU/L in individuals aged over 80 years [15, 87].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [87]
Ethnicity influences thyroid hormone levels, which could produce an aberrant test where the local population that supplied subjects for determining the reference range is mainly of a different ethnicity to the patient.
“Ethnicity also influences thyroid hormone levels, which could produce an aberrant test where the local population that supplied subjects for determining the reference range is mainly of a different ethnicity to the patient [26].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [26]
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 [94]
The citation lists haven’t been fetched yet
References 39 · Cited by 258
- Authors
- Surks, M. I., & Boucai, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Surks, Martin I.
- ORCID
- Boucai, Laura
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-02-01
- Volume
- 95
- Issue
- 2
- Pages
- 496-502
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2166619307
- Cited by
- 258
- References
- 39
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 12 · 2023: 9 · 2022: 12 · 2021: 12 · 2020: 10 · 2019: 22 · 2018: 21 · 2017: 19 · 2016: 24 · 2015: 16 · 2014: 17 · 2013: 27 · 2012: 14
- FWCI
- 1.71
- 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 › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- serum thyrotropin, age-related reference values, racial and ethnic differences, skewed distributions, mild hypothyroidism, thyroid dysfunction, subpopulation differences, genetic factors
- MeSH terms
- Adult, Age Factors, Aged, Humans, Middle Aged, Reference Values, Thyroid Diseases, Thyrotropin, Thyroxine, Black People, White People
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
