Multidisciplinary approach to redefining thyroid hormone reference intervals with big data analysis

Objectives: This study aimed to employ big data analysis to harmonize reference intervals (RI) for thyroid function tests, with refinement to the TSH upper reference limit, and to optimize the TSH reflex algorithm to improve clinical management and test utilization. Design & methods: TSH, free T4, and free T3 results tested in Alberta, Canada, on Roche Cobas and Siemens Atellica were extracted from the laboratory information system (N = 1,144,155 for TSH, N = 183,354 for free T4 and N = 92,632 for free T3). Results from specialists, inpatients, or repeat testing, as well as from positive thyroid disease, autoimmune disease, and pregnancy biomarkers were excluded. RIs were derived using statistical models (Bhattacharya, refineR, and simple non-parametric) followed by endocrinology and laboratory review. Results: The TSH RIs for 0 to 7 days, 8 days to 1 year, and >= 1 year were 1.23 to 25.0 mIU/L, 1.00 to 6.80 mIU/L and 0.20 to 6.50 mIU/L, respectively. The free T4 RIs for 0 to 14 days, 15 to 29 days, and >= 30 days were 13.5 to 50.0 pmol/L, 8.7 to 32.5 pmol/L, and 10.0 to 25.0 pmol/L, respectively. An updated TSH reflex algorithm was developed based on the optimized TSH and free T4 RIs, with free T4 reflexed only at a TSH of <0.1 mIU/L. Conclusions: The collaboration of a multidisciplinary team and the utilization of big data analysis led to the enhancement of thyroid function RIs, specifically resulting in the widening of the upper TSH reference limit to 6.50. Application of these optimized RIs with the TSH reflex algorithm will serve as a guide for improvement in interpretation of thyroid function tests.