Reference Ranges for Thyroid-Stimulating Hormone and Free Thyroxine in Older Men: Results From the Health In Men Study

Background: In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men. Methods: We conducted the study on community-dwelling men aged 70-89 years. Baseline TSH and FT4 levels were assayed (Elecsys 2010, Roche Diagnostics). Conventional reference intervals for TSH and FT4 were 0.4-4.0 mIU/L and 10-23 pmol/L, respectively. Incident deaths were ascertained using data linkage. Results: Of the 3,885 men included in the analysis, the 2.5th and 97.5th centiles for TSH and FT4 were 0.64-5.9 mIU/L and 12.1-20.6 pmol/L (0.94-1.60 ng/dL), respectively. Of the 411 very healthy men defined by excellent or very good self-rated health and absence of major medical comorbidities, 2.5th to 97.5th centiles for TSH and FT4 were 0.67-4.98 mIU/L and 12.1-20.5 pmol/L (0.94-1.59 ng/dL), respectively. TSH was not associated with mortality, whereas higher FT4 was associated with increased mortality. Applying intervals based on very healthy older men to the cohort as a whole led to the reclassification of 310 men (8.0%). More men were classified as being hyperthyroid or hypothyroid, or having subclinical hyperthyroidism, and fewer as having subclinical hypothyroidism. Conclusions: In older men, the reference interval for TSH in older men is shifted upward, whereas the reference interval for FT4 is compressed compared with the conventional reference ranges. Applying reference intervals based on healthy older men identifies a substantial number of older men as having overt thyroid disease or subclinical hyperthyroidism and reduces the number classified as having subclinical hypothyroidism.