Age-specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction

The use of age-specific reference ranges for TSH is advocated, but the impact of this on laboratory diagnosis of thyroid dysfunction is unclear. Our aims were to determine age-specific TSH reference ranges and to examine interassay differences in performance.

We analysed TSH results from 223,045 consecutive samples assayed over 1 year by a single pathology provider using the Siemens Centaur assay. We excluded patients with evidence of thyroid disease to derive a reference population of 148,938 individuals and analysed results in the 5-year age bands. We reassayed 120 samples using three other methods (Architect, Roche and Immulite) to assess precision and bias.

The 2·5th percentile for TSH was consistent across age groups (approximately 0·5 mU/l), whereas the 97·5th percentile increased from age 40 upwards, with the reference range upper limit being 3·75 mU/l at age 40 and 5·0 mU/l at age 90. In most age bands, the use of age-specific upper limits reclassified only 0·1-1·9% of participants as normal or abnormal compared with a common cut-off of 4·0 mU/l; in participants aged 85 years or more, reclassification rates were higher (2·1-4·7%). The four TSH assays showed good agreement at low-normal TSH concentrations (<2 mU/l), but at concentrations of 4·0 mU/l, there were intermethod differences of approximately 1 mU/l.

The use of age-specific reference ranges for TSH has only minor effects on thyroid status, except in the very old. At high-normal TSH concentrations, between-method differences in performance have a comparable impact to that of age and may affect clinical decision-making.