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Age-Specific Reference Intervals for Thyroid-Stimulating Hormones and Free Thyroxine to Optimize Diagnosis of Thyroid
Heleen I Jansen1,2,3, Niek F Dirks3,4,5, Jacquelien J Hillebrand2,3
1Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam, The Netherlands.
Insights
Establishing age-specific reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is crucial. Using adult TSH age-specific intervals can reduce hypothyroidism diagnoses in older adults.
Area of Science:
- Clinical Chemistry
- Endocrinology
- Laboratory Medicine
Background:
- Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) are vital for diagnosing thyroid disease.
- Current laboratory RIs often lack age-specificity beyond childhood, despite known age-related variations in TSH.
- This limitation may lead to misclassification of thyroid function in adults.
Purpose of the Study:
- To establish age-specific RIs for TSH and FT4 throughout the lifespan.
- To evaluate the impact of using these age-specific RIs on adult thyroid disease diagnoses.
Main Methods:
- A multicenter retrospective cross-sectional study utilizing big data from 13 Dutch laboratories (2008-2022).
- Determination of indirect RIs for TSH and FT4 using TMC and refineR-analysis across four immunoassay platforms.
- Establishment of age groups from 2 to 100 years, with specific categories for childhood, adulthood, and older age.
Main Results:
- Significant age-related variations in TSH and FT4 RIs were observed, with higher upper limits in childhood decreasing into adulthood.
- TSH upper RIs increased in adults from age 50 (women) and 60 (men), while FT4 upper RIs increased from age 70.
- Application of adult age-specific TSH RIs led to a reduction in subclinical and overt hypothyroidism diagnoses in older adults (women >50, men >60) on the Roche platform.
Conclusions:
- Age-specific RIs are essential for accurate TSH and FT4 interpretation, particularly in children.
- Implementing age-specific TSH RIs in adults is clinically relevant for reducing overdiagnosis of hypothyroidism in the elderly.
- Further research is needed to establish uniform and clinically applicable age-specific FT4 RIs.
Abstract:
Background: Thyroid-stimulating hormone (TSH) and subsequent free thyroxine (FT4) concentrations outside the reference interval (RI) are used to diagnose thyroid diseases. Most laboratories do not provide age-specific RIs for TSH and FT4 beyond childhood, although TSH concentrations vary with age. Therefore, we aimed to establish TSH and FT4 age-specific RIs throughout life and aimed to determine whether using these RIs would result in reclassification of thyroid disease diagnoses in adults. Methods: This multicenter retrospective cross-sectional study used big data to determine indirect RIs for TSH and FT4. These RIs were determined by TMC and refineR-analysis, respectively, using four different immunoassay platforms (Roche, Abbott, Siemens, and Beckman Coulter). Retrospective data (2008-2022) from 13 Dutch laboratories for general practitioners and local hospitals were used. RIs were evaluated per manufacturer. Age groups were established from 2 to 20 years by 2-year categories and decade categories between 20 and 100 years. Results: We included totally 7.6 million TSH and 2.2 million FT4 requests. TSH upper reference limits (URLs) and FT4 lower reference limits were higher in early childhood and decreased toward adulthood. In adulthood, TSH URLs increased from 60 years in men, and from 50 years in women, while FT4 URLs increased from 70 years onward. Using adult age-specific RIs resulted in a decrease in diagnoses of subclinical and overt hypothyroidism in women above 50 and men above 60 years in our Roche dataset. Conclusion: This study stressed the known importance of using age-specific RIs for TSH and FT4 in children. This study also showed the clinical relevance of using age-specific RIs for TSH in adulthood to reduce diagnoses of subclinical hypothyroidism in older persons. Therefore, implementation of adult TSH age-specific RIs should be strongly considered. Data are less uniform regarding FT4 age-specific RIs and more research should be performed before implementing these in clinical practice.
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