Age-specific reference intervals for TSH and FT4 to optimize diagnosis of thyroid disease

Heleen Jansen; Niek Dirks; Jacquelien Hillebrand; Boekel Edwin Ten; Jacoline Brinkman; Madelon Buijs; Ayse Demir; Ineke Dijkstra; Silvia Endenburg; Paula Engbers; Jeannette Gootjes; Marcel Janssen; Stephan Kamphuis; Jong Wilhelmina Kniest-de; Adrian Kruit; Etienne Michielsen; Albert Wolthuis; Trotsenburg A.S. Paul van; Heijer Martin den; Eveline Bruinstroop; Anita Boelen; Annemieke C Heijboer; Elzen Wendy den

doi:10.1530/endoabs.99.RC6.1

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Endocrine Abstracts (2024) 99 RC6.1 | DOI: 10.1530/endoabs.99.RC6.1

ECE2024 Rapid Communications Rapid Communications 6: Thyroid | Part I (5 abstracts)

Age-specific reference intervals for TSH and FT4 to optimize diagnosis of thyroid disease

Heleen Jansen ^1,2,3 , Niek Dirks ^2,4,5 , Jacquelien Hillebrand ^2,3 , Edwin Ten Boekel ⁵ , Jacoline Brinkman ⁶ , Madelon Buijs ⁴ , Ayse Demir ⁷ , Ineke Dijkstra ⁸ , Silvia Endenburg ⁹ , Paula Engbers ¹⁰ , Jeannette Gootjes ⁴ , Marcel Janssen ¹¹ , Stephan Kamphuis ¹² , Wilhelmina Kniest-de Jong ¹³ , Adrian Kruit ¹⁴ , Etienne Michielsen ¹⁵ , Albert Wolthuis ¹⁶ , A.S. Paul van Trotsenburg ^3,17 , Martin den Heijer ^3,18 , Eveline Bruinstroop ^3,19 , Anita Boelen ^2,3,20 , Annemieke C Heijboer ^1,2,3,20 & Wendy den Elzen ^21,22

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¹Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam, Netherlands; ²Amsterdam UMC location University of Amsterdam, Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam, Netherlands; ³Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, Netherlands; ⁴Atalmedial Diagnostic Centers, Amsterdam, Amsterdam, Netherlands; ⁵Northwest Clinics, Alkmaar, Department of Clinical Chemistry, Hematology & Immunology, Alkmaar, Netherlands; ⁶St. Jansdal Hospital, Harderwijk, Department of Clinical Chemistry, Harderwijk, Netherlands; ⁷Meander Medical Center, Amersfoort, Laboratory for Clinical Chemistry and Hematology, Amersfoort, Netherlands; ⁸St Antonius Hospital, Nieuwegein, Department of Clinical Chemistry, Nieuwegein, Netherlands; ⁹Dicoon, Gelderse Vallei Hospital, Ede, Department of Clinical Chemistry and Hematology, Ede, Netherlands, ¹⁰Treant Zorggroep, Hoogeveen, Department of Clinical Chemistry, Hoogeveen, Netherlands, ¹¹VieCuri Medical Center, Venlo, Laboratory of Clinical Chemistry and Hematology, Venlo, Netherlands, ¹²Eurofins Clinical Diagnostics, Eurofins Gelre, Apeldoorn, Netherlands, ¹³Saltro Diagnostic Center, Unilabs Netherlands, Utrecht, Netherlands, ¹⁴Nij Smellinghe Hospital, Drachten, Medical Laboratory, Drachten, Netherlands, ¹⁵Diagnostiek voor U, Eindhoven, Eindhoven, Netherlands, ¹⁶Stichting Certe Medische Diagnostiek en Advies, Groningen, Groningen, Netherlands, ¹⁷Emma Children’s Hospital, Amsterdam UMC location University of Amsterdam, Department of Paediatric Endocrinology, Amsterdam, Netherlands, ¹⁸Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, Netherlands, ¹⁹Amsterdam UMC location University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, Netherlands, ²⁰Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands, ²¹Amsterdam UMC location University of Amsterdam, Department of Laboratory Medicine, Laboratory Specialized Diagnostics & Research, Amsterdam, Netherlands, ²²Amsterdam Public Health, Amsterdam, Netherlands

Introduction: Thyroid disorders are generally diagnosed based on thyroid stimulating hormone (TSH) outside the reference interval (RI), and subsequent free thyroxine (FT4) concentrations. Most laboratories do not provide age-specific RIs for TSH and FT4 beyond childhood, although it is known that TSH concentrations vary with age which may be important to take into account. Therefore, we aimed to establish age-specific RIs for TSH and FT4 throughout life using an indirect method for four commonly used immunoassay platforms. Also, we determined whether using age-specific RIs would result in reclassification of thyroid disease diagnoses in adults.

Methods: Indirect RIs for TSH (TMC) and FT4 (RefineR) using four different immunoassay platforms (Roche, Abbott, Siemens, Beckman) were established using retrospective data from 13 Dutch laboratories (>7 million TSH and >2 million FT4 unique requests). RIs were evaluated per manufacturer. Age groups were established from 2 to 20 years by 2-year categories, followed by decade categories between 20 and 100 years.

Results: TSH upper reference limits (URLs) and FT4 lower reference limits (LRLs) were higher until the age of 10 to 12 years and decreased towards adulthood. The URLs of FT4 were stable with a dip during puberty. In adulthood, TSH URLs increased from the age of 60 years onwards, and even from 50 years in women, while FT4 URLs increased from 70 years onwards. The LRLs of TSH and FT4 remained stable during ageing. The use of our adult age-specific RIs resulted in a decrease in diagnoses of subclinical and overt hypothyroidism in women above 50 (15.7 to 7.3% and 2.7 to 2.3%, respectively), and in men above 60 years of age (13.7 to 8% and 2.0 to 1.6%, respectively) in our Roche dataset.

Conclusion: This study stressed the known importance of using age-specific RIs in children. In adulthood, age-specific reference intervals are currently not used in clinical practice. However, this study showed an important clinical relevance by reducing the diagnoses of subclinical hypothyroidism, and to a lesser extent, overt hypothyroidism. Therefore, implementation of adult TSH age-specific RIs in clinical practice should be strongly considered. Data is less uniform regarding FT4 age-specific RIs and more research should be performed before implementing these in clinical practice.