Assessment of central adrenal insufficiency in children and adolescents with Prader-Willi syndrome

Objective A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of PraderWilli syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 mu g] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS. Design Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre. Patients Eighty-four children with PWS. Measurements Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-mu g tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients clinical and molecular characteristics to assess genotypephenotype correlation. Results Pathological cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who had reduced basal (169.4 +/- 83.3 nm) and stimulated (428.1 +/- 69.6 nm) cortisol levels compared to patients with normal responses (367.1 +/- 170.6 and 775.9 +/- 191.3 nm, P < 0.001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0.001), and the patients ages (P < 0.001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0.030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r2 = 0.353, P < 0.001). Standard-dose (250 mu g) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the cohort). Conclusions Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood.