Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study
-
Cammie Tran
, Duncan J. Topliss
, Ego Seeman
Abstract
Objectives
As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over.
Methods
A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had no history of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time.
Results
A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8–77.3) years. We propose a RI of 0.34–3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI.
Conclusions
From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.
Funding source: National Health and Medical Research Council
Award Identifier / Grant number: 1127060
Award Identifier / Grant number: 334047
Award Identifier / Grant number: IG1173690
Funding source: National Institute on Aging
Award Identifier / Grant number: U01AG029824
Award Identifier / Grant number: U19AG062682
Funding source: National Cancer Institute
Award Identifier / Grant number: 5U01AG029824-02
Acknowledgments
The authors acknowledge Dr. Suzanne Orchard and Mr. James Phung for their role and contribution in the ASPREE Healthy Ageing Biobank sub-study. The authors would also like to acknowledge the ASPREE participants and are grateful for their time and participation in this study, the general practitioners and medical clinics who support the participants, and dedicated ASPREE staff members for the conduct of the ASPREE trial and ASPREE-XT observational follow-on period.
-
Research ethics: Ethics approval for the principal ASPREE trial, ASPREE-XT observational study and the ALSOP sub-study was obtained from the Monash University Human Research Ethics Committee (2006/745MC and CF11/1100), and for ASPREE-XT and ASPREE Healthy Ageing Biobank from the Alfred Hospital Ethics Committee (HREC/17/Alfred/198 and 18/08). Written consent was obtained from all participants.
-
Informed consent: Written consent was obtained from all participants.
-
Author contributions: Ms Tran and Drs Clayton-Chubb and Zhou had full access to and verified the data of the study. Professor McNeil was the senior author. Drafting and editing of the manuscript: Tran, Topliss, Schneider, Seeman, Clayton-Chubb, Neumann, Kakoly, Zhou, Hussain, Rickard, Clark, Shah, Woods and McNeil. Concept and design: Tran, Topliss, Schneider, McNeil. Data acquisition, analysis, interpretation: Tran, Ball, Clayton-Chubb, Zhou, Hussain. Content validation: Topliss, Schneider, Seeman, Neumann, Woods, McNeil. Funding acquisition: Schneider, Woods, McNeil. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: Neumann reports speaker/consulting honoraria from Siemens Healthineers, Roche and PHC. Schneider receives Reagent Grant from Abbott Diagnostics for the assays measured. All other authors state no conflict of interest.
-
Research funding: The ASPREE clinical trial and ASPREE-XT was supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (U01AG029824, U19AG062682); the NHMRC (334047, 1127060); Monash University; and Alfred Health. The ASPREE Biobank was supported by research grants from the Australian Government’s CSIRO (Commonwealth Scientific and Industrial Research Organisation; Preventative Health Flagship 2009) and the National Cancer Institute/NIH (5U01AG029824-02). Author McNeil is an NHMRC leadership fellow (IG1173690). The study was supported by a reagent grant of Abbott Diagnostics and research funds of the Alfred Pathology service. The funders did not have any influence on the design of the research study or the decision to publish.
-
Data availability: The de-identified dataset used for this analysis can be accessible to researchers and students via a request to http://ams.aspree.org.
References
1. So, M, MacIsaac, RJ, Grossmann, M. Hypothyroidism investigation and management. Aust J Gen Pract 2012;41:556–62.Search in Google Scholar
2. Dedon, J. Thyroid disease in aging. Mo Med 2022;119:351–3.Search in Google Scholar
3. Vadiveloo, T, Donnan, PT, Murphy, MJ, Leese, GP. 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). J Clin Endocrinol Metabol 2013;98:1147–53. https://doi.org/10.1210/jc.2012-3191.Search in Google Scholar PubMed
4. Schalin-Jäntti, C, Tanner, P, Välimäki, MJ, Hämäläinen, E. Serum TSH reference interval in healthy Finnish adults using the Abbott Architect 2000i Analyzer. Scand J Clin Lab Invest 2011;71:344–9. https://doi.org/10.3109/00365513.2011.568630.Search in Google Scholar PubMed
5. Ni, W, Zhang, M, Wang, X, Li, X, Wang, Q, Wang, Y, et al.. Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population. Sci Rep 2022;12. https://doi.org/10.1038/s41598-022-24182-w.Search in Google Scholar PubMed PubMed Central
6. Topliss, DJ. What happens when laboratory reference ranges change? Can Med Assoc J 2020;192:E481–2. https://doi.org/10.1503/cmaj.200511.Search in Google Scholar PubMed PubMed Central
7. McNeil, JJ, Woods, RL, Nelson, MR, Reid, CM, Kirpach, B, Wolfe, R, et al.. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med 2018;379:1499–508. https://doi.org/10.1056/nejmoa1800722.Search in Google Scholar PubMed PubMed Central
8. McNeil, JJ, Woods, RL, Nelson, MR, Murray, AM, Reid, CM, Kirpach, B, et al.. Baseline characteristics of participants in the ASPREE (ASPirin in reducing events in the elderly) study. J Gerontol A Biol Sci Med Sci 2017;72:1586–93. https://doi.org/10.1093/gerona/glw342.Search in Google Scholar PubMed PubMed Central
9. Ernst, ME, Broder, JC, Wolfe, R, Woods, RL, Nelson, MR, Ryan, J, et al.. Health characteristics and aspirin use in participants at the baseline of the ASPirin in reducing events in the elderly – eXTension (ASPREE-XT) observational study. Contemp Clin Trials 2023;130:107231. https://doi.org/10.1016/j.cct.2023.107231.Search in Google Scholar PubMed PubMed Central
10. McNeil, JJ, Wolfe, R, Woods, RL, Tonkin, AM, Donnan, GA, Nelson, MR, et al.. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018;379:1509–18. https://doi.org/10.1056/nejmoa1805819.Search in Google Scholar
11. McNeil, JJ, Nelson, MR, Woods, RL, Lockery, JE, Wolfe, R, Reid, CM, et al.. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018;379:1519–28. https://doi.org/10.1056/nejmoa1803955.Search in Google Scholar
12. Ball, J, Neumann, JT, Tonkin, AM, Kirchhof, P, Freedman, B, Brodtmann, A, et al.. Low-dose aspirin and incident atrial fibrillation in healthy older individuals: a post-hoc analysis of the ASPREE trial. Eur Heart J Cardiovasc Pharmacother 2024;10:81–2. https://doi.org/10.1093/ehjcvp/pvad082.Search in Google Scholar PubMed PubMed Central
13. Barker, AL, Morello, R, Thao, LTP, Seeman, E, Ward, SA, Sanders, KM, et al.. Daily low-dose aspirin and risk of serious falls and fractures in healthy older people: a substudy of the ASPREE randomized clinical trial. JAMA Intern Med 2022;182:1289–97. https://doi.org/10.1001/jamainternmed.2022.5028.Search in Google Scholar PubMed PubMed Central
14. McNeil, JJ, Woods, RL, Ward, SA, Britt, CJ, Lockery, JE, Beilin, LJ, et al.. Cohort profile: the ASPREE longitudinal study of older persons (ALSOP). Int J Epidemiol 2019;48:1048–9h. https://doi.org/10.1093/ije/dyy279.Search in Google Scholar PubMed PubMed Central
15. Parker, EJ, Orchard, SG, Gilbert, TJ, Phung, JJ, Owen, AJ, Lockett, T, et al.. The ASPREE healthy ageing biobank: methodology and participant characteristics. PLoS One 2024;19:e0294743. https://doi.org/10.1371/journal.pone.0294743.Search in Google Scholar PubMed PubMed Central
16. National Association of Testing Authorities. Specific Accreditation Guidance: scope of accreditation – service descriptors for human pathology [Internet]. NATA 2024. Available from: http://nata.com.au/files/2021/05/SoA-descriptors-Human-Pathology.pdf Search in Google Scholar
17. Henny, J, Vassault, A, Boursier, G, Vukasovic, I, Mesko Brguljan, P, Lohmander, M, et al.. Recommendation for the review of biological reference intervals in medical laboratories. Clin Chem Lab Med 2016;54:1893–900. https://doi.org/10.1515/cclm-2016-0793.Search in Google Scholar PubMed
18. Hollowell, JG, Staehling, NW, Flanders, WD, Hannon, WH, Gunter, EW, Spencer, CA, et al.. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): national health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metabol 2002;87:489–99. https://doi.org/10.1210/jcem.87.2.8182.Search in Google Scholar PubMed
19. Mokhtar, KM. TSH continuous reference intervals by indirect methods: a comparisons to partitioned reference intervals. Clin Biochem 2020;85:53–6. https://doi.org/10.1016/j.clinbiochem.2020.08.003.Search in Google Scholar PubMed
20. Aw, TC, Sickan, J, Du, SX, Li, J, Janel, H, Beshiri, A. Reference intervals for TSH on the architect analyser based on the National Academy of Clinical Biochemistry (NACB) guidelines derived from healthy multi-ethnic Asians attending a community health fair. Int Arch Endocrinol Clin Res 2019;5:015.Search in Google Scholar
21. González-Sagrado, M, Martín-Gil, FJ. Population-specific reference values for thyroid hormones on the Abbott ARCHITECT i2000 analyzer. Clin Chem Lab Med 2005;42:540–2. https://doi.org/10.1515/cclm.2004.091.Search in Google Scholar PubMed
22. Yeap, BB, Manning, L, Chubb, SAP, Hankey, GJ, Golledge, J, Almeida, OP, et al.. Reference ranges for thyroid-stimulating hormone and free thyroxine in older men: results from the health in men study. J Gerontol A Biol Sci Med Sci 2016;72:444–9. https://doi.org/10.1093/gerona/glw132.Search in Google Scholar PubMed
23. Aghini Lombardi, F, Fiore, E, Tonacchera, M, Antonangeli, L, Rago, T, Frigeri, M, et al.. The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later. J Clin Endocrinol Metabol 2013;98:1031–9. https://doi.org/10.1210/jc.2012-2960.Search in Google Scholar PubMed
24. Guan, H, Shan, Z, Teng, X, Li, Y, Teng, D, Jin, Y, et al.. Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes. Clin Endocrinol 2008;69:136–41. https://doi.org/10.1111/j.1365-2265.2007.03150.x.Search in Google Scholar PubMed
25. Ittermann, T, Khattak, RM, Nauck, M, Cordova, CM, Völzke, H. Shift of the TSH reference range with improved iodine supply in Northeast Germany. Eur J Endocrinol 2015;172:261–7. https://doi.org/10.1530/eje-14-0898.Search in Google Scholar
26. Riis, J, Kragholm, K, Torp-Pedersen, C, Andersen, S. Association between thyroid function, nursing home admission and mortality in community-dwelling adults over 80 years. Arch Gerontol Geriatr 2023;104:104806. https://doi.org/10.1016/j.archger.2022.104806.Search in Google Scholar PubMed
27. Segna, D, Bauer, DC, Feller, M, Schneider, C, Fink, HA, Aubert, CE, et al.. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med 2018;283:56–72. https://doi.org/10.1111/joim.12688.Search in Google Scholar PubMed PubMed Central
28. Sohn, SY, Lee, E, Lee, MK, Lee, JH. The association of overt and subclinical hyperthyroidism with the risk of cardiovascular events and cardiovascular mortality: meta-analysis and systematic review of cohort studies. Endocrinol Metabol 2020;35:786–800. https://doi.org/10.3803/enm.2020.728.Search in Google Scholar PubMed PubMed Central
29. Sun, J, Yao, L, Fang, Y, Yang, R, Chen, Y, Yang, K, et al.. Relationship between subclinical thyroid dysfunction and the risk of cardiovascular outcomes: a systematic review and meta-analysis of prospective cohort studies. Int J Endocrinol 2017;2017:8130796. https://doi.org/10.1155/2017/8130796.Search in Google Scholar PubMed PubMed Central
30. Svensson, J, Ohlsson, C, Karlsson, MK, Lorentzon, M, Lewerin, C, Mellström, D. Subclinical hyperthyroidism is associated with increased risk of vertebral fractures in older men. Osteoporos Int 2021;32:2257–65. https://doi.org/10.1007/s00198-021-05964-w.Search in Google Scholar PubMed PubMed Central
31. Chaker, L, Wolters, FJ, Bos, D, Korevaar, TI, Hofman, A, van der Lugt, A, et al.. Thyroid function and the risk of dementia: the Rotterdam Study. Neurology 2016;87:1688–95. https://doi.org/10.1212/wnl.0000000000003227.Search in Google Scholar PubMed
32. Ogliari, G, Smit, RAJ, Van Der Spoel, E, Mari, D, Torresani, E, Felicetta, I, et al.. Thyroid status and mortality risk in older adults with normal thyrotropin: sex differences in the Milan Geriatrics 75+ cohort study. J Gerontol A Biol Sci Med Sci 2016:glw113. https://doi.org/10.1093/gerona/glw113.Search in Google Scholar PubMed
33. Panday, P, Arcia Franchini, AP, Iskander, B, Anwer, F, Oliveri, F, Kakargias, F, et al.. Subclinical hypothyroidism in Geriatric population and its association with heart failure. Cureus 2021;13:e14296. https://doi.org/10.7759/cureus.14296.Search in Google Scholar PubMed PubMed Central
34. Tsai, TY, Tu, YK, Munir, KM, Lin, SM, Chang, RH, Kao, SL, et al.. Association of hypothyroidism and mortality in the elderly population: a systematic review and meta-analysis. J Clin Endocrinol Metab 2020;105. https://doi.org/10.1210/clinem/dgz186.Search in Google Scholar PubMed
35. Rosario, PW, Calsolari, MR. TSH reference range in older adults: a Brazilian study. Arq Bras Endocrinol Metabol 2014;58:389–93. https://doi.org/10.1590/0004-2730000003065.Search in Google Scholar PubMed
36. Fu, J, Wang, Y, Liu, Y, Song, Q, Cao, J, Peichang, W. Reference intervals for thyroid hormones for the elderly population and their influence on the diagnosis of subclinical hypothyroidism. J Med Biochem 2023;42:258–64. https://doi.org/10.5937/jomb0-39570.Search in Google Scholar PubMed PubMed Central
© 2024 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorials
- Multi-cancer early detection: searching for evidence
- High sensitivity cardiac troponin assays, rapid myocardial infarction rule-out algorithms, and assay performance
- Reviews
- Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine
- Copeptin as a diagnostic and prognostic biomarker in pediatric diseases
- Opinion Papers
- The Unholy Grail of cancer screening: or is it just about the Benjamins?
- Critical appraisal of the CLSI guideline EP09c “measurement procedure comparison and bias estimation using patient samples”
- Tumor markers determination in malignant pleural effusion: pearls and pitfalls
- Contribution of laboratory medicine and emerging technologies to cardiovascular risk reduction via exposome analysis: an opinion of the IFCC Division on Emerging Technologies
- Guidelines and Recommendations
- Recommendations for European laboratories based on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
- Genetics and Molecular Diagnostics
- Expanded carrier screening for 224 monogenic disease genes in 1,499 Chinese couples: a single-center study
- General Clinical Chemistry and Laboratory Medicine
- How do experts determine where to intervene on test ordering? An interview study
- New concept for control material in glucose point-of-care-testing for external quality assessment schemes
- Vitamin B12 deficiency in newborns: impact on individual’s health status and healthcare costs
- Analytical evaluation of eight qualitative FIT for haemoglobin products, for professional use in the UK
- Colorimetric correcting for sample concentration in stool samples
- Reference Values and Biological Variations
- Assessment of canonical diurnal variations in plasma glucose using quantile regression modelling and Chronomaps
- Inconsistency in ferritin reference intervals across laboratories: a major concern for clinical decision making
- Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study
- Hematology and Coagulation
- The EuroFlow PIDOT external quality assurance scheme: enhancing laboratory performance evaluation in immunophenotyping of rare lymphoid immunodeficiencies
- Clinical value of smear review of flagged samples analyzed with the Sysmex XN hematology analyzer
- Cardiovascular Diseases
- Evidence for stability of cardiac troponin T concentrations measured with a high sensitivity TnT test in serum and lithium heparin plasma after six-year storage at −80 °C and multiple freeze-thaw cycles
- Letters to the Editor
- Impact of high-sensitivity cardiac troponin I assay imprecision on the safety of a single-sample rule-out approach for myocardial infarction
- Why is single sample rule out of non-ST elevation myocardial infarction using high-sensitivity cardiac troponin T safe when analytical imprecision is so high? A joint statistical and clinical demonstration
- Iron deficiency and iron deficiency anemia in transgender populations: what’s different?
- The information about the metrological traceability pedigree of the in vitro diagnostic calibrators should be improved: the case of plasma ethanol
- Time to refresh and integrate the JCTLM database entries for total bilirubin: the way forward
- Navigation between EQA and sustainability
- C-terminal alpha-1-antitrypsin peptides as novel predictor of hospital mortality in critically ill COVID-19 patients
- Neutralizing antibodies against KP.2 and KP.3: why the current vaccine needs an update
- A simple gatekeeping intervention improves the appropriateness of blood urea nitrogen testing
- Congress Abstracts
- 16ª Reunião Científica da Sociedade Portuguesa de Medicina Laboratorial - SPML
Articles in the same Issue
- Frontmatter
- Editorials
- Multi-cancer early detection: searching for evidence
- High sensitivity cardiac troponin assays, rapid myocardial infarction rule-out algorithms, and assay performance
- Reviews
- Consensus statement on extracellular vesicles in liquid biopsy for advancing laboratory medicine
- Copeptin as a diagnostic and prognostic biomarker in pediatric diseases
- Opinion Papers
- The Unholy Grail of cancer screening: or is it just about the Benjamins?
- Critical appraisal of the CLSI guideline EP09c “measurement procedure comparison and bias estimation using patient samples”
- Tumor markers determination in malignant pleural effusion: pearls and pitfalls
- Contribution of laboratory medicine and emerging technologies to cardiovascular risk reduction via exposome analysis: an opinion of the IFCC Division on Emerging Technologies
- Guidelines and Recommendations
- Recommendations for European laboratories based on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
- Genetics and Molecular Diagnostics
- Expanded carrier screening for 224 monogenic disease genes in 1,499 Chinese couples: a single-center study
- General Clinical Chemistry and Laboratory Medicine
- How do experts determine where to intervene on test ordering? An interview study
- New concept for control material in glucose point-of-care-testing for external quality assessment schemes
- Vitamin B12 deficiency in newborns: impact on individual’s health status and healthcare costs
- Analytical evaluation of eight qualitative FIT for haemoglobin products, for professional use in the UK
- Colorimetric correcting for sample concentration in stool samples
- Reference Values and Biological Variations
- Assessment of canonical diurnal variations in plasma glucose using quantile regression modelling and Chronomaps
- Inconsistency in ferritin reference intervals across laboratories: a major concern for clinical decision making
- Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study
- Hematology and Coagulation
- The EuroFlow PIDOT external quality assurance scheme: enhancing laboratory performance evaluation in immunophenotyping of rare lymphoid immunodeficiencies
- Clinical value of smear review of flagged samples analyzed with the Sysmex XN hematology analyzer
- Cardiovascular Diseases
- Evidence for stability of cardiac troponin T concentrations measured with a high sensitivity TnT test in serum and lithium heparin plasma after six-year storage at −80 °C and multiple freeze-thaw cycles
- Letters to the Editor
- Impact of high-sensitivity cardiac troponin I assay imprecision on the safety of a single-sample rule-out approach for myocardial infarction
- Why is single sample rule out of non-ST elevation myocardial infarction using high-sensitivity cardiac troponin T safe when analytical imprecision is so high? A joint statistical and clinical demonstration
- Iron deficiency and iron deficiency anemia in transgender populations: what’s different?
- The information about the metrological traceability pedigree of the in vitro diagnostic calibrators should be improved: the case of plasma ethanol
- Time to refresh and integrate the JCTLM database entries for total bilirubin: the way forward
- Navigation between EQA and sustainability
- C-terminal alpha-1-antitrypsin peptides as novel predictor of hospital mortality in critically ill COVID-19 patients
- Neutralizing antibodies against KP.2 and KP.3: why the current vaccine needs an update
- A simple gatekeeping intervention improves the appropriateness of blood urea nitrogen testing
- Congress Abstracts
- 16ª Reunião Científica da Sociedade Portuguesa de Medicina Laboratorial - SPML