Quinty Leusink1, Paul Span2, Fred Sweep3, Hedi Claahsen-van der Grinten4, Teun van Herwaarden3
(1) Department of Laboratory Medicine, Department of Pediatric Endocrinology, Radboudumc, Nijmegen, Nederland.
(2) Department of Radiation Oncology, Radboudumc, Nijmegen, Nederland.
(3) Department of Laboratory Medicine, Radboudumc, Nijmegen, Nederland.
(4) Department of Pediatric Endocrinology, Radboudumc, Nijmegen, Nederland.
Congenital adrenal hyperplasia (CAH) comprises a group of rare autosomal recessive disorders caused by enzymatic defects in adrenal steroidogenesis, primarily due to a 21-hydroxylase deficiency (21OHD), affecting 1 in 15,000 individuals. This deficiency impairs cortisol synthesis, leading to elevated precursor steroids and adrenal androgens (AA). Especially AA excess is responsible for many complications, i.e., precocious puberty, impaired final height, and infertility. Glucocorticoid treatment aims for cortisol supplementation and normalization of AA concentrations. Current monitoring relies on androstenedione (A4) and 17-hydroxyprogesterone. While A4 is the most commonly used biomarker for hyperandrogenism and treatment titration, it is unable to differentiate between adrenal and gonadal origin in pubertal age, limiting optimal correlation with clinical parameters. 11-oxygenated androgens (11OA) are adrenal-specific and the most abundant androgens in 21OHD, representing promising biomarkers for 21OHD monitoring. However, 11OA are not yet implemented in routine care as reference values are lacking. This study explores the potential clinical value of 11OA for treatment monitoring in pediatric 21OHD patients. Patients routinely collect saliva, facilitating non-invasive, home-based monitoring. Samples are taken in the morning, afternoon and evening, to capture the diurnal rhythm of AA secretion. Multiplexed steroid profiles, including classic biomarkers and 11OA, are quantified using a newly-developed liquid-chromatography tandem mass-spectrometry (LC-MS/MS) assay. This project establishes age-specific salivary reference intervals for 11OA from 200 healthy controls, stratified by sex, age and timepoint of sampling. A two-year longitudinal trial in 60-80 patients (0-17 years) evaluates the clinical relevance of 11OA to optimize treatment control and long-term outcomes in pediatric 21OHD patients.