Verification of Reference Interval of Thyroid Hormones With Manual and Automated Indirect Approaches: Comparison of Hoffman, KOSMIC and refineR Methods

Abstract

Introduction: The interpretation of quantitative test results requires the availability of appropriate reference intervals (RIs). Every laboratory has been advised by scientific literature and reagent manufacturers to establish RIs for all analytes. Measuring RIs using direct methods is very costly, and it poses ethical and practical challenges. To overcome these challenges, indirect methods, such as Hoffman, and newer automated approaches, such as KOSMIC and refineR, are used to verify RIs for thyroid hormones. Objective: To verify RIs for thyroid hormones in adult patients using Hoffman, KOSMIC and refineR methods and to compare these with reference ranges given in kit literature or standard textbooks. Materials and methods: The observed values (results) of thyroid hormone were collected from the LIS (Laboratory Information System) of the Biochemistry Department at the B. J. Medical College and Civil Hospital in Ahmedabad between 1 January 2021 and 31 May 2022. Hoffman, KOSMIC and refineR methods were used to verify the RIs. The computerised Hoffman approach, which Katayev et al. describe, is a simple method for determining RI from hospital data. Zierk et al. pre-validated and suggested the KOSMIC method based on Python programming, whereas refineR was proposed by Tatjana et al. based on R programming language. Results: Hoffman, KOSMIC and refineR’s indirect RI techniques revealed comparable results with kit literature in free T3 and T4, whereas higher upper reference limits of thyroid-stimulating hormone (TSH) compared to kit literature were observed with KOSMIC and refineR methods. However, the computerised Hoffman method revealed comparable results with TSH also. Conclusion: Indirect approaches, such as Hoffman, KOSMIC and refineR, provide reliable RI verification for free T3 and T4 utilising patient samples obtained from LIS. However, the manual Hoffman method provides reliable RI verification for TSH data derived from the hospital population as compared to automated approaches, such as KOSMIC and refineR.