Age‐specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction
Abstract
Summary: Objective: The use of age‐specific reference ranges for TSH is advocated, but the impact of this on laboratory diagnosis of thyroid dysfunction is unclear. Our aims were to determine age‐specific TSH reference ranges and to examine interassay differences in performance. Design: We analysed TSH results from 223 045 consecutive samples assayed over 1 year by a single pathology provider using the S iemens C entaur assay. We excluded patients with evidence of thyroid disease to derive a reference population of 148 938 individuals and analysed results in the 5‐year age bands. We reassayed 120 samples using three other methods (A rchitect, R oche and I mmulite) to assess precision and bias. Results: The 2·5th percentile for TSH was consistent across age groups (approximately 0·5 m U/l), whereas the 97·5th percentile increased from age 40 upwards, with the reference range upper limit being 3·75 m U/l at age 40 and 5·0 m U/l at age 90. In most age bands, the use of age‐specific upper limits reclassified only 0·1–1·9% of participants as normal or abnormal compared with a common cut‐off of 4·0 m U/l; in participants aged 85 years or more, reclassification rates were higher (2·1–4·7%). The four TSH assays showed good agreement at low‐normal TSH concentrations (<2 m U/l), but at concentrations of 4·0 m U/l, there were intermethod differences of approximately 1 m U/l. Conclusion: The use of age‐specific reference ranges for TSH has only minor effects on thyroid status, except in the very old. At high‐normal TSH concentrations, between‐method differences in performance have a comparable impact to that of age and may affect clinical decision‐making.
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A study from Western Australia suggested that age-specific TSH reference intervals exerted only a negligible impact on the diagnosis of thyroid dysfunction in the elderly population.
“A study from Western Australia suggested that age-specific TSH reference intervals exerted only a negligible impact on the diagnosis of thyroid dysfunction in the elderly population [109].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [109]
In this study, only about 1-2% of individuals aged over 65 years were misclassified using the general adult reference intervals.
“In this study, only about 1–2% of individuals aged over 65 years were misclassified using the general adult reference intervals [109].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [109]
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“Thus, moderately old patients (65–75 years) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value (around 2–3 mIU/l), whereas oldest old subjects (>80–85 years) should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment (18,…”
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“0 mU/L has only minor effects on thyroid status, except in the very old ( 85 years old).(10) Thus, a TSH level >4 mU/L was considered as subclinical hypothyroidism in the present study.”
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“The present study, describing the physiological changes in pituitary-thyroid axis function which occur during adolescence, clarifies findings of previous cross-sectional studies of age-dependency of thyroid function tests, which gave inconsistent results (7, 10, 11, 29, 30, 31, 32, 33).”
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“However, other studies from UK and Australia reported that serum TSH level was higher in males than in females [6, 8].”
Reference intervals for neonatal thyroid function tests in the first 7 days of life
Jayasuriya, M. S., Choy, K. W., Chin, L. K., Doery, J. C. G., Stewart, A., Bergman, P. B., & Lu, Z. X. (2018) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2018-0007 · Cited by 20 · see citing works
TSH-independent release of thyroid hormones through cold exposure in aging rats
Park, G. C., Kim, J. M., Park, H., Han, J. M., Shin, S., Jang, J. Y., Jung, D., Kim, I. J., Lee, J., & Lee, B. (2017) · Oncotarget · doi:10.18632/oncotarget.19851 · Cited by 20 · see citing works
“Understanding on the mechanism behind the low levels of thyroid hormones despite the high levels of TSH in elderly individuals is still lacking [14-16].”
BackgroundWang, X., Li, Y., Zhai, X., Wang, H., Zhang, F., Gao, X., Liu, S., Teng, W., & Shan, Z. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.660277 · Cited by 19 · see citing works
Kim, J., Prasitlumkum, N., Randhawa, S., & Banerjee, D. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10153318 · Cited by 21 · see citing works
Reflex TSH strategy: the good, the bad and the ugly
Plebani, M., & Giovanella, L. (2019) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2019-0625 · Cited by 19 · see citing works
“b) TSH cutoffs are strongly affected by the different accuracies of immunoassays, because inter method differences of about 1 mU/L at concentrations of 4–5 mU/L have been reported [9].”
BackgroundIs an Isolated TSH Elevation in Chronic Nonthyroidal Illness “Subclinical Hypothyroidism”?
Kaptein, E. M., LoPresti, J. S., & Kaptein, M. J. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1850 · Cited by 17 · see citing works
“TSH assays are poorly harmonized among laboratories, and values may be higher due to assay variability rather than to thyroid gland failure (36).”
BackgroundDuccini, K., de Souza, M. V. L., Delfim, R. L. C., Aguiar, A. P., Teixeira, P. D. F. D. S., & Vaisman, M. (2018) · Medical Principles and Practice · doi:10.1159/000488196 · Cited by 16 · see citing works
TSH Reference Limits: New Concepts and Implications for Diagnosis of Subclinical Hypothyroidism
Surks, M. I. (2013) · Endocrine Practice · doi:10.4158/ep13246.co · Cited by 15 · see citing works
The Impact of Antiepileptic Drugs on Thyroid Function in Children with Epilepsy: New Versus Old.
Elshorbagy, H. H., Barseem, N. F., Suliman, H. A., Talaat, E., Al-shokary, A. H., Abdelghani, W. E., Abdulsamea, S. E., Maksoud, Y. H. A., Azab, S. M., Elsadek, A. E., et al. (2020) · Iranian journal of child neurology. · doi:10.22037/ijcn.v14i1.19177 · Cited by 13 · see citing works
Ma, C., Zhong, J., Zou, Y., Liu, Z., Li, H., Pang, J., Liu, X., Zejipuchi, Tian, L., Hou, L., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.816970 · Cited by 12 · see citing works
“In addition, the RIs established for thyroid-related hormones may be only applicable to the Roche platform, as non-negligible discrepancy among assay methodologies has been revealed (13).”
BackgroundLiu, Y., Milanesi, A., & Brent, G. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813814-4.00021-3 · Cited by 12 · see citing works
Dirinck, E. L., Dirtu, A. C., Malarvannan, G., Covaci, A., Jorens, P. G., & Gaal, L. V. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13040421 · Cited by 12 · see citing works
“TSH tends to increase during the lifespan [4,5], and is influenced by gender [6].”
BackgroundXiong, J., Liu, S., Hu, K., Xiong, Y., Wang, P., & Xiong, L. (2020) · PLoS ONE · doi:10.1371/journal.pone.0239579 · Cited by 12 · see citing works
“A study has also shown the minimal impact of serum TSH concentrations on the diagnosis of thyroid dysfunction [13].”
BackgroundBarth, J. H., Spencer, J. D., Goodall, S. R., & Luvai, A. (2016) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563216636897 · Cited by 11 · see citing works
“Kahapola-Arachchige et al.(15) Advia Centaur 14,363 data mining 0.”
BackgroundPediatric reference values of TSH should be personalized according to BMI and ethnicity
Oron, T., Lazar, L., Feldhamer, I., Manor, M., Koren-Morag, N., Tenenbaum, A., & Meyerovitch, J. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0239 · Cited by 10 · see citing works
Wang, P., Gao, Y., Cheng, J., Kong, G.-Q., Wang, Y., Wu, X., Zhao, Z. G., & Yuan, H. (2014) · Genetics and Molecular Research · doi:10.4238/2014.april.14.15 · Cited by 10 · see citing works
“In contrast, some previous studies reported that the median and range of TSH concentration increase with age (Boucai and Surks, 2009; Surks and Boucai, 2010; Kahapola-Arachchige et al., 2012; Vadiveloo et al., 2013).”
ResultChen, J., Zhou, W., Pan, F., Cui, W., Li, M., & Hu, Y. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0113 · Cited by 10 · see citing works
Subclinical Hypothyroidism: is it Really Subclinical with Aging?
Gourmelon, R., Donadio, S., Chikh, K., Rabilloud, M., Kuczewski, E., Gauchez, A., Charrié, A., Brard, P.-Y., Andreani, R., Bourre, J. C., et al. (2018) · Aging and Disease · doi:10.14336/ad.2018.0817 · Cited by 10 · see citing works
Razvi, S., Jabbar, A., Addison, C., Vernazza, J., Syed, A. A., Soran, H., & Leng, O. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad016 · Cited by 10 · see citing works
Suzuki, S., Suzuki, S., Iwadate, M., Matsuzuka, T., Shimura, H., Ohira, T., Furuya, F., Suzuki, S., Yasumura, S., Yokoya, S., et al. (2022) · Thyroid · doi:10.1089/thy.2022.0327 · Cited by 9 · see citing works
Thyrotropin reference interval in older adults
Zhai, X., Li, Y. J., Teng, X., Teng, W., Shi, X., & Shan, Z. (2024) · Endocrine Connections · doi:10.1530/ec-24-0435 · Cited by 9 · see citing works
“Between 1981 and 1994, researchers in Australia conducted a study and discovered that participants who had the lowest TSH levels at baseline showed the most signi fi cant increase in TSH over time.”
Pankiv, V. І. (2017) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.13.2.2017.100604 · Cited by 9 · see citing works
Thyroid Hormone Reference Intervals among Healthy Individuals In Lanzhou, China
Lu, Y., Zhang, W.-X., Li, D., Wei, L., Zhang, Y., Shi, F.-N., & Zhou, S. (2023) · Endocrinology and Metabolism · doi:10.3803/enm.2023.1638 · Cited by 8 · see citing works
“Some studies showed minor effects of age on TSH reference ranges; however, in those studies, the median TSH level increased with age in participants aged >85 years [45,46].”
Razvi, S., Leng, O., Jabbar, A., Bano, A., Ingoe, L. E., Addison, C., Thomas, H. E., Carey, P. E., Junejo, S., Austin, D., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz143 · Cited by 8 · see citing works
TSH reference range in older adults: a Brazilian study
Rosário, P. W., & Calsolari, M. R. (2014) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/0004-2730000003065 · Cited by 8 · see citing works
“Therefore, the adoption of a different limit for the elderly population would have an impact on subjects with intermediate TSH levels, who may be erroneously classified as having subclinical hypothyroidism (SCH) or as inadequately treated if undergoing L-T4 replacement therapy; however, the representativeness of these…”
BackgroundBarhanovic, N. G., Antunović, T., Kavarić, S., Djogo, A., & Spasojevic, V. K. (2018) · Journal of Medical Biochemistry · doi:10.2478/jomb-2018-0020 · Cited by 8 · see citing works
“By contrast to a study performed in Western Australia (30), we had a significantly high percentage of females in the two youngest groups classified differently when the calculated age-specific upper TSH reference limits were applied.”
ResultTSH and T4 Levels in a Cohort of Depressive Patients.
Costache, A. C., Riza, A., Popescu, M., Dinca, M., Glavan, D.-G., Vladu, I. M., Ioana, M. I., & Udriștoiu, I. (2020) · PubMed Central · doi:10.12865/chsj.46.02.03 · Cited by 5 · see citing works
“The questions that rises is whether we should be using age-specific reference TSH ranges to reduce the number of patients unnecessarily treated with thyroid hormone replacement [22].”
BackgroundCardiovascular Manifestations of Primary Hypothyroidism
Shrestha, S., Lamsal, K. S., Shreshtha, B. D., & Bajracharya, S. B. (2022) · Med Phoenix · doi:10.3126/medphoenix.v6i2.36794 · Cited by 6 · see citing works
Diagnosing and treating the elderly individual with hypopituitarism
Corsello, A., Paragliola, R. M., & Salvatori, R. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09870-w · Cited by 4 · see citing works
Chaker, L., & Peeters, R. P. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-99899-4.00015-9 · Cited by 4 · see citing works
An enumeration of the prevalence of hypothyroidism during pregnancy in central India
Bose, A., Soni, N., Dashore, N., Gajria, K., Jhamad, S., Hemvani, N., & Chitnis, D. S. (2015) · Clinical Epidemiology and Global Health · doi:10.1016/j.cegh.2015.11.004 · Cited by 3 · see citing works
A bivariate reference interval for TSH and free thyroxine
Åsberg, A., & Mikkelsen, G. (2024) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2024.2437613 · Cited by 3 · see citing works
“Those are rounded 2.5 and 97.5 percentiles in the distribution of s-TSH measured by the Siemens Centaur assay in a large thyroid-healthy population in Western Australia [5].”
InfluentialQuelle pertinence accorder au taux circulant de TSH ?
Donadio, S., Chikh, K., Iss, C., Kuczewski, E., Gauchez, A., Ronin, C., & Charrié, A. (2013) · Immuno-analyse & Biologie Spécialisée · doi:10.1016/j.immbio.2013.03.007 · Cited by 3 · see citing works
Genetics of Thyroid Function: Relevance for Biology and Disease Management
Sterenborg, R. B. T. M., Peeters, R. P., Visser, W. E., Kuś, A., Smit, J. W. A., Teumer, A., & Medici, M. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf491 · Cited by 2 · see citing works
Xu, Y., Hysaj, O., Qi, X., Feller, M., Pingitore, A., Brown, S. J., Ittermann, T., Iacoviello, M., Trompet, S., Han, J. W., et al. (2026) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(26)00009-4 · Cited by 2 · see citing works
Self-citationMaternal Thyroid Hormones and Ageing Process
(2018) · International journal of research studies in biosciences · doi:10.20431/2349-0365.0602005 · Cited by 1 · see citing works
“These disturbances can increase the risk of longevity (Cooper and Biondi, 2012; Kahapola-Arachchige et al., 2012; Gesing, 2015; Hennessey et al., 2015).”
BackgroundShalamai, U. P., Zayats, О. V., & Voronych-Semchenko, N. (2021) · Fìzìologìčnij žurnal · doi:10.15407/fz67.03.035 · Cited by 1 · see citing works
“У групи дітей з належним забезпеченням йодом (1-ша та 2-га) включали за умови, якщо концентрація мікроелемента в сечі знаходилась у межах від 100 до 300 мкг/л, у групи з легким йододефіцитом (3-тя та 4-та) – вміст йоду в сечі знаходився у межах 50–99 мкг/л [10, 11].”
Meirelles-Cardoso, T. B. B. C., Slhessarenko, N., & Fontes, C. J. F. (2023) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-4292-2022-0499 · Cited by 1 · see citing works
“The analysis of the studies that used the same age groups as those of the children studied here also showed variability in the RIs, most likely due to other methodological heterogeneities, such as sample origin or data source and device used to determine serum TSH concentrations (5,22,38,39,41).”
BackgroundMethodResultInfluentialPankiv, V. І. (2017) · Reproductive Endocrinology · doi:10.18370/2309-4117.2017.35.84-88 · Cited by 1 · see citing works
Santhosh Viswan, B., Gurulakshmi, G., Bi, A. K., Subbarayalu, S., & Surendran, G. (2020) · Biomedical & Pharmacology Journal · doi:10.13005/bpj/2047 · Cited by 1 · see citing works
Faut-il faire un dosage systématique de la TSH à l’admission en court séjour gériatrique ?
Kobeh, D., Janin, H., Regueme, S. C., & Bourdel‐Marchasson, I. (2017) · NPG. Neurologie, psychiatrie, gériatrie/NPG · doi:10.1016/j.npg.2017.05.007
Reference Interval of Serum Thyroid Hormone in Obese Thais
Lerttrakul, P., Rerkngarm, T., & Bordeerat, N. K. (2018)
Intervalli di riferimento del TSH in Italia: uno studio geoepidemiologico a due siti
Tozzoli, R., Serio, F. D., Metus, P., & Brescia, V. (2020) · La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine · doi:10.23736/s1825-859x.20.00064-x
Mater, N. K., Ahmed, R. S., & Shamran, H. A. (2023) · AIP conference proceedings · doi:10.1063/5.0150905
Biochemical Diagnosis of Thyroid Dysfunctions
Giovanella, L., D’Aurizio, F., & Ovčariček, P. P. (2023) · Springer eBooks · doi:10.1007/978-3-031-35213-3_3
Predictors of Serum TSH in a Healthy Adult Sample of the Lebanese Population
Achkar, A., Mourad, D., Naous, E., Sleilaty, G., & Gannagé‐Yared, M. (2022) · Annals of Thyroid Research · doi:10.26420/annalsthyroidres.2022.1089
Guglielmi, R., Mian, C., Andreoli, C., Bagnasco, M., Boniardi, M., Menis, E. D., Rimini, M. L. D., Tina, D., Fiorentini, G., Locantore, P., et al. (2025) · L Endocrinologo · doi:10.1007/s40619-025-01601-4
Age-related reference intervals for thyroid function tests are beneficial in adults over 60 years
Allen, G. F. G., Blampied, S., Patel, K. A., McDonald, T. J., Hattersley, A. T., & Vaidya, B. (2026) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/00045632261426852
Akşit, M. (2026) · Turkish Journal of Biochemistry · doi:10.1515/tjb-2025-0424
Mise en oeuvre de dosages pour le diagnostic précoce de l'hypothyroïdie
Iss, C. (2015) · theses.fr (ABES) · doi:10.70675/f9f2aeebza5a8z4cf3zb9afzd52e7504b286
- Authors
- Kahapola‐Arachchige, K. M., Hadlow, N., Wardrop, R., Lim, E. M., & Walsh, J. P.
- Affiliations
- Western Diagnostic Pathology Myaree WA Australia
- Queen Elizabeth II Medical Centre (AU)
- Sir Charles Gairdner Hospital (AU)
- The University of Western Australia (AU)
- Corresponding author
- Walsh, John P.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2012-10-05
- Volume
- 77
- Issue
- 5
- Pages
- 773-779
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2060612220
- Semantic Scholar
- 0453e0299067515a76d7ea91d2e9116daae8657e
- Cited by
- 95
- References
- 36
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 11
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Abbott Laboratories
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- TSH reference range, age-specific reference ranges, thyroid dysfunction, oldest old, thyroid function tests
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Reference Values, Thyroid Diseases, Thyrotropin, Age Distribution, Young Adult
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