In Review | Thyroid Updates 2025  | Gerontology | Thyroid Function Tests

Rethinking Thyroid Function in Ageing Adults: Why TSH Reference Ranges Matter

This article is a compilation of recent studies published in a number of peer-reviewed publications. It is not intended to represent original research, nor is it intended to replace the original research.  Access the full Disclaimer Information.
 

Diagnosing thyroid disorders in older adults often presents a clinical challenge.

Subclinical hypothyroidism, in particular, is frequently identified based on TSH levels that fall outside of standard adult reference intervals. However, these intervals are often derived from younger populations and may not accurately reflect what constitutes normal thyroid function in older adults.
 
Consequently, there is increasing concern that current diagnostic approaches may lead to overdiagnosis and overtreatment in this elderly cohort, with no appreciable benefit from such treatment.
 
Clinical guidelines from bodies such as the European Thyroid Association (ETA) recommend a more conservative approach to treating subclinical hypothyroidism in older adults, but many practitioners continue to prescribe levothyroxine even when diagnostic thresholds are not met.
 
A recent large-scale analysis, published in Thyroid on 15 November 2025, sought to determine how age-specific reference intervals for TSH could affect the diagnosis of subclinical hypothyroidism.¹
 
Researchers applied these tailored reference ranges to a dataset that included over 280,000 adults —194,856 women and 85,215 men.
 
The study also explored the impact of these changes on prescribing practices and treatment outcomes, particularly in relation to the use of levothyroxine in older adults. It examined whether applying age-appropriate cut-offs could reduce unnecessary diagnoses and treatments, and whether doing so would have any adverse effects on thyroid function indicators such as TSH and free thyroxine (FT4).
 
The results showed that using age-specific TSH reference intervals significantly reduced the diagnosis rates of subclinical hypothyroidism in older adults.
 

Among women aged 50–60 years, the prevalence dropped from 13.1% to 8.6%.  In those aged 90–100 years, it fell from 22.7% to 8.1%.

Similar reductions were seen in men: for those aged 60–70 years, diagnoses declined from 10.9% to 7.7%, and from 27.4% to 9.6% in the 90–100 age group.

Importantly, the impact on the diagnosis of overt hypothyroidism was less pronounced, with only modest decreases observed across different age groups.
 
No significant changes were noted in the diagnosis of subclinical hyperthyroidism, underscoring the specificity of the effect in cases of subclinical hypothyroidism.

 
The study also addressed the implications for treatment. Despite the high prevalence of subclinical hypothyroidism in those over 80 years of age, existing evidence—including large, randomized trials—shows no clear benefit of levothyroxine in this age group. Nevertheless, the hormone is still commonly prescribed.

Applying age-specific TSH ranges suggested that nearly one-third of older patients currently being treated could safely discontinue levothyroxine without negatively affecting thyroid function.
 
Emerging data also indicate that slightly elevated TSH levels may even confer benefits in adults over 80, further questioning the need for pharmacological intervention in this population.
 

Implications in Practice
 

SEMDSA/ACE-SA Guideline for the Management of Hypothyroidism in Adults, released in 2015, indicates that practitioners should maintain a high index of suspicion for hypothyroidism in elderly patients (> 65 years) as they may lack the typical symptoms and signs.

Specifically, the guidelines indicate that there is strong evidence that the serum TSH level is higher in elderly individuals (> 65 years), and a target TSH level on LT4 replacement therapy of 4.0-6.0 mIU/L may be appropriate in those > over 65. ²

While some have suggested that age-specific reference ranges should be used when interpreting TSH levels, these have not been validated in the South African setting.
 
The study under review here, however, reinforces the clinical value of adopting age-older adults. Reducing overdiagnosis has significant implications: it can alleviate patient anxiety, lower the burden on healthcare providers, and reduce unnecessary follow-up appointments and treatments.
 
Researchers highlighted that a modest rise in TSH may be a normal physiological response to ageing rather than a sign of disease. They suggested that this should inform both diagnostic and treatment strategies.

However, the researchers also noted implementation challenges, particularly that TSH reference ranges can vary depending on the assay used, making standardisation difficult across clinical laboratories. There is a call for more flexible guidelines that acknowledge the variability of testing methods and move away from rigid thresholds that may not apply across all age groups or laboratory platforms.
 
The study, presented at the 2024 American Thyroid Association (ATA) meeting in November 2024, was recognised as a pivotal contribution to clinical thyroidology. 
 
Overall, this research supports a more nuanced, evidence-based approach to diagnosing and managing subclinical hypothyroidism. Tailoring reference intervals by age could play a key role in improving patient care while promoting more efficient and appropriate use of healthcare resources.

 

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