Endocrine Abstracts

JOINT2462

Background: Central adrenal insufficiency (CAI) is a severe endocrinological manifestation reported in Prader Willi Syndrome (PWS). To date there is no consensus on the most reliable dynamic test to assess the adrenal function or whether to treat CAI. We aimed to evaluate adrenal function using morning plasma cortisol (MPC) and Low-Dose Tetracosactrin Stimulation Test (LDTST) in a paediatric PWS cohort; we also evaluated the usefulness of Glucagon stimulation test (GST) in those in transitional age who reached adult height.

Methods: We retrospectively analysed MPC and ACTH levels in 94 GH-treated PWS patients (48:M, 46: F), aged 0.5–17.9 years, followed at San Raffaele Hospital over the past 16 years. An MPC level of ≥60 ng/mL was considered normal; a LDTST test was performed if MPC was lower than 60 ng/ml on two MPC measurements. A cortisol peak <180 ng/mL after LDTST was suggestive of CAI. We also assessed hypothalamic–pituitary–adrenal (HPA) function in those patients undergoing GST during transitional age at adult height achievement; in this case adrenal insufficiency was considered as peak of cortisol <167 ng/mL, according to prior studies.

Results: The median MPC and ACTH levels were 75.5 ng/mL [54; 109] and 16 pg/ml [12; 22.38], respectively. No patients showed laboratory abnormalities suggestive of CAI, such as hypoglycaemia, hyponatremia, or hyperkalaemia. Only one patient (1%) presented abnormal weight loss, albeit in absence of anorexia, fatigue or salt cravings. Eight subjects (8.5%) underwent LDTST: median basal and peak cortisol levels were 40 ng/ml [30.5; 55.75] and 185 ng/ml [149.3; 217.3], respectively. Four out of eight patients (50%) showed a pathological test response, although the cortisol peak was not indicative of severe CAI. These patients were advised to take hydrocortisone only during acute illness or stressful events. Total of nine patients (9.5%) underwent GST during transitional age, all showing an adequate cortisol response (median peak 198 ng/ml [172.5; 216]).

Conclusions: This study suggests that CAI, despite rare, is a potentially life-threatening endocrinological manifestation in PWS. Considering its subtle presentation, monitoring adrenal function in PWS patients is crucial. Morning basal cortisol alone has a limited diagnostic value for CAI, but it appears useful as an initial step in CAI screening. To improve diagnostic accuracy, we believe that a dynamic stimulation test should be performed in every PWS patient at least once. Further studies are needed to establish defined criteria for diagnosis and treatment of CAI.