ESPE2021 Free Communications Adrenal (6 abstracts)
Salivary profiles of 11 oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia
Hanna F. Nowotny 1 , Matthias K. Auer 1 , Christian Lottspeich 1 , Heinrich Schmidt 2 , Ilja Dubinski 2 , Martin Bidlingmaier 1 , Jo Adaway 3 , James Hawley 3 , Brian Keevil 3 & Nicole Reisch 1
1Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munich, Germany.;2Department of Pediatric Endocrinology, Dr. von Haunersches Children’s Hospital, Klinikum der Universität München, LMU München, Munich, Germany.;3Department of Clinical Biochemistry, Manchester University Foundation NHS Trust, Manchester Academic Health Sciences Centre, Southmoor Rd, Manchester, United Kingdom
Background: Routine biochemical assessment in patients with congenital adrenal hyperplasia (CAH) includes measurement of serum 17 hydroxyprogesterone (17OHP), androstenedione (A4) and testosterone (T) and their metabolites in urine. Several studies have also described 11 oxygenated 19 carbon (11oxC19) steroids as a clinically relevant androgenetic source and highlighted their potential as markers for evaluation of adrenal androgen excess in patients with 21-hydroxylase deficiency (21OHD).
Methods: Cross sectional single center study including 34 patients with classic 21OHD (men = 14; women = 20) and 32 BMI- and age matched controls (men = 15; women = 17). Saliva was collected at five different timepoints throughout the day adjusted to intake of glucocorticoid medication. Salivary concentrations of the following steroids were analyzed by LC MS/MS: 17OHP, A4, T, 11β hydroxyandrostenedione (11OHA4) and 11 ketotestosterone (11KT).
Results: Similar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11 OHA4: male patients Δmean= 79 %; male controls Δmean= 81%; female patients Δmean= 33 %; female controls Δmean= 91 %; 11KT: male patients Δmean= 64 %; male controls Δmean= 60 %; female patients Δmean= 49 %; female controls Δmean= 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male = 0.741**; r(p)female = 0.842****), and 11OHA4 (r(p)male = 0.385n.s.; r(p)female = 0.527*) were observed in patients but not in controls. P-value ≤ 0.05 (*), ≤ 0.01 (**), ≤ 0.001 (***), ≤ 0.0001 (****).
Conclusions: This study is the first to describe the diurnal rhythm of 11oxC19 steroids in salivary profiles in both healthy controls as well as patients with CAH due to 21OHD. Adrenal 11oxC19 androgens are clearly secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.
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