Background

Thyroid disorders are generally diagnosed based on thyroid stimulating hormone (TSH) outside the reference interval (RI), and subsequent free thyroxine (FT4) concentrations. Most laboratories do not provide age-dependent RIs for TSH and FT4 beyond childhood, although it is known that taking age into account is important, e.g. in the neonatal period. Therefore, we aimed to establish TSH and FT4 age-dependent RIs throughout life using an indirect method for four frequently used immunoassay platforms, and determined whether using age-dependent RIs would lead to reclassification of thyroid diagnoses in adults.

Methods

Indirect RIs for TSH (TMC) and FT4 (RefineR) using four immunoassay platforms (Roche, Abbott, Siemens, Beckman) were established using retrospective data from 13 Dutch laboratories (>7 million TSH and >2 million FT4 requests). RIs were assessed per manufacturer. Age groups were established from 2-18 years by categories of 2 years, and in adults by an age-category “18-20 years”, followed by decade categories between ages 20 and 100 years.

Results

TSH upper reference limit (URL) and FT4 lower reference limit (LRL) were higher in childhood and decreased towards adulthood. The URL of FT4 was stable with a dip during puberty. In adulthood, TSH URL increased from 60 years, and even from 50 years in women, while FT4 URL increased from 70 years onwards. The LRL of TSH and FT4 remained stable during ageing. The use of our adult age-dependent RIs would lead to a decrease in diagnosis of subclinical and overt hypothyroidism in women above 50 (15.7 to 7.3% and 2.7 to 2.3%, respectively), and in men above 60 years of age (13.7 to 8% and 2.0 to 1.6%, respectively).

Conclusion

TSH URL and FT4 LRL were higher in childhood, stressing the importance of using age-dependent RIs in children. TSH and FT4 URL increased with higher age in adulthood. Furthermore, using age-dependent adult RIs for TSH and FT4 is likely to have impact on diagnosing hypothyroidism, and its implementation in clinical practice should thus be subject of debate.