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Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study

  • Cammie Tran ORCID logo EMAIL logo , Duncan J. Topliss , Hans G. Schneider ORCID logo , Ego Seeman , Daniel Clayton-Chubb , Johannes T. Neumann , Nadira Kakoly , Zhen Zhou , Sultana Monira Hussain , Amanda J. Rickard , David P.Q. Clark , Raj C. Shah , Robyn L. Woods and John J. McNeil
Published/Copyright: October 3, 2024

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.


Corresponding author: Cammie Tran, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne 3004 VIC, Australia, E-mail:

Award Identifier / Grant number: 1127060

Award Identifier / Grant number: 334047

Award Identifier / Grant number: IG1173690

Award Identifier / Grant number: U01AG029824

Award Identifier / Grant number: U19AG062682

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.

  1. 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.

  2. Informed consent: Written consent was obtained from all participants.

  3. 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.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. 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.

  6. 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.

  7. 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.

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Received: 2024-07-22
Accepted: 2024-08-30
Published Online: 2024-10-03
Published in Print: 2025-02-25

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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