ESPE Abstracts (2018) 89 RFC1.6

A Laboratory Harmonization Strategy for Steroid Hormone Profiling by MoM-Transformed, Normalized Reference Ranges Independent of Age, Sex and Units

Alexandra E Kullea, Dominika Zalasb, Thomas Reinehrc, Marek Niedzielab, Christoph Borzikowskyd, Francisca Pintoa, Juliane Baumanna, Maciej Fladerb, Gunter Simic-Schleichere, Halit Ilker Akkurtf, Sabine Hegerg, Nadine Horniga & Paul-Martin Holterhusa


aUniversity Medical Center SH, Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Kiel, Germany; bPoznan University of Medical Sciences, Department of Pediatric Endocrinology and Rheumatology, Poznan, Poland; cUniversity of Witten/Herdecke, Vestische Hospital for Children and Adolescents, Datteln, Germany; dUniversity Medical Center SH, Institute of Medical Informatics and Statistics, Kiel, Germany; eChildren’s Hospital of Bremen-Nord, Bremen, Germany; fChildren’s Hospital Altona, Pediatric Endocrinology, Hamburg, Germany; gChildren’s Hospital “Auf der Bult”, Hannover, Germany


Background/aims: The high complexity of Pediatric reference ranges across age, sex and units impairs clinical application and comparability of steroid hormone data, e.g., in CAHs. We developed a Multiples-of-Median (MoM) normalization tool to overcome this major drawback in Pediatric Endocrinology.

Methods: LC–MS/MS data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to >16 years) from two previous datasets were MoM-transformed across age and sex. 24 genetically proven CAH patients were included (21OHD, N=19; 11OHD, N=5). MoM cut-offs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, N=8; adrenal cortical carcinoma, N=6; obesity, N=40).

Results: 21OHD and 11OHD showed disease-typical, easily recognizable MoM-patterns independent of age, sex and concentrations units. Two single-steroid cut-offs indicated 21OHD: 3.87 MoM for 17Hydroxyprogesterone (100% sensitivity, 98.83% specificity) and 12.28 MoM for 21Deoxycortisol (94.74% sensitivity, 100% specificity). A 13.18 MoM for 11Deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity).

Conclusions: Age- and sex-independent MoMs are straightforward for clinically relevant display of multisteroid patterns. In addition, defined single steroid MoMs can serve alone as predictors for 21OHD and 11OHD. Finally, MoM-transformation offers substantial enhancement of routine - and scientific steroid hormone data exchange due to improved comparability.