ISSN : 2663-2187

“ Decoding Thyroid Metrics: Establishing Reference Intervals with the Indirect Hoffmann Method on the ADVIA Centaur Analyzer.”

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Dr B SHESHU KUMAR, Dr NISMA NAYEEM, Dr G VIDYA
» doi: 10.48047/AFJBS.6.12.2024. 4076-4093

Abstract

Background: The accurate diagnosis and cost effective monitoring of thyroid function parameters such as thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) are crucial for managing thyroid disease. TSH, with its high sensitivity in detecting subclinical thyroid dysfunction, is typically measured using third generation methods with a sensitivity of 0.01 mIU/L. However, challenges remain in standardizing and harmonizing these methods, impacting the interpretation of laboratory results and clinical decisions. Variability in TSH reference intervals (RIs) due to regional iodine intake and analytical methods necessitates establishing RIs tailored to specific populations rather than relying on manufacturer provided values. 1,2,3 According to CLSI recommendations, an RI is defined as the interval within which 95% of values from a reference population are expected to fall. This interval includes two extreme reference limits, which are derived from the distribution of reference values. These lim its represent boundaries associated not only with good health but also with potential physiological or pathological conditions. Establishing accurate RIs based on these guidelines is crucial for ensuring reliable interpretation of laboratory test results a nd for making informed clinical decisions related to patient health and disease management.This methodological choice ensures that RIs accurately reflect the local population's thyroid function parameters, enhancing diagnostic precision and clinical utilit y in medical practice. 6,7,8 AIMS & OBJECTIVES: The study aimed to establish reference intervals (RIs) for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and the FT3/FT4 ratio using indirect statistical methods. Data from thyroid function tests conducted between 2020 and 2024 were analyzed, with RIs determined based on the 2.5th and 97.5th percentiles according to IFCC guidelines (CLSI C28 A3). METHODS: We analyzed 1220 thyroid stimulating hormone (TSH), free thyrox ine (FT4), and free triiodothyronine (FT3) results collected from 2020 to 2024 using a Siemens ADVIA Centaur XP analyzer with chemiluminescent immunoassay (CLIA) technology. Reference intervals (RIs) were established using the 2.5th and 97.5th percentiles, as per IFCC guidelines (CLSI C28 A3). To address skewed distributions, TSH and FT4 data underwent logarithmic transformation and were categorized into eight age groups from infancy to over 80 years. Outliers were identified and excluded using the two side d Tukey test. The Hoffman method, validated through Q Q plots, determined RIs based on ln transformed values. Further refinement involved visual outlier elimination and linear regression models with high correlation coefficients (r > 0.99) to calculate ref erence limits adjusted to a 95% confidence interval. The final RIs, obtained through antilogarithm transformation, were clinically significant and supported by Reference Change Value (RCV) calculations. This rigorous methodological approach ensures the rel iability and applicability of the RIs for accurate interpretation of thyroid function tests across diverse age groups in clinical practice. RESULTS: The established reference intervals (RIs) for TSH, FT4, FT3, and the FT3/FT4 ratio were determined as fol lows: 0.33 4.11 mIU/L for TSH, 11.5 20.8 pmol/L for FT4, 3.8 6.44 pmol/L for FT3, and 0.23 0.49 for the FT3/FT4 ratio. These RIs exhibited significant deviations from the manufacturer recommended values for TSH and FT4. Moreover, FT3 levels showed notable increases in individuals under 30 years compared to those in their fourth (5.28 vs. 5.00, p=0.0048), fifth (5.27 vs. 4.98, p=0.001), sixth (5.27 vs. 4.89, p<0.001), seventh (5.29 vs. 4.82, p<0.001) decades, and those older than 70 years (5.27 vs. 4.58, p<0 .001). Significant variations (p <0.001) in TSH values and the FT3/FT4 ratio were also evident across different age groups. CONCLUSIONS: The reference intervals (RIs) established for the Republic of Srpska showed notable differences from the manufacturer's recommended RIs, especially for thyroid stimulating hormone (TSH) and free thyroxine (FT4). These findings highlight the need for region specific RIs for thyroid parameters, in line with Clinical and Laboratory Standards Institute (CLSI) guidelines. The s tudy recommends that other laboratories adopt similar CLSI methodologies to ensure accurate, context specific RIs, which will improve clinical interpretation and management of thyroid disorders across diverse populations.

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