Endocrine Abstracts

Introduction: Individuals with Prader-Willi syndrome (PWS) have hypothalamic dysfunction, with deficiencies of several hypothalamic-pituitary axes. Prevalence of central hypogonadism, hypothyroidism and growth hormone deficiency are increased in comparison with non-PWS individuals. Central adrenal insufficiency (CAI) has also been reported in PWS. Several studies, using different testing modalities, have reported strikingly differing prevalences of CAI in PWS, ranging from 0% to 60%. It is speculated that CAI may be responsible, in part, for high mortality (3%) in patients with PWS. If CAI is present, timely diagnosis and treatment is needed in order to prevent avoidable mortality. Due to the lack of consensus, there are no guidelines or recommendations on the appropriate evaluation and management of CAI in the adult PWS population. Many adults patients with PWS receive standard hydrocortisone (HC) stress dose during physical and/or psychological stress. Frequent administration of HC increases the risk of obesity, hypertension, osteoporosis and diabetes, already a major problem in adults with PWS. It is therefore of utmost importance to assess the prevalence of CAI in order to prevent overtreatment with HC.

Methods: We screened medical histories of all patients for symptoms of CAI. We performed multiple dose metyrapone (MTP) test in 47 adults with genetically confirmed PWS. At day one, oral MTP 750 mg (Laboratoire HRA Pharma, Paris, France) was administered orally every 4 hours, starting from 0800 h. At 0800 h on day two, blood was drawn for determining 11-deoxycortisol (11-DOC) levels. At both days, blood was drawn after 8 hours fasting. Levels of 11-DOC greater than 7.6 g/dl (230 nmol/l) were classified as adrenal sufficiency.

Results: Median (IQR) age of participants was 28.8 (22.8–35.5). Twenty were using GH treatment since childhood. Male/female ratio was 28/19. Revision of medical histories revealed that a substantial part of patients had undergone operations or had infections without receiving HC stress dose, without any negative consequences. All 47 patients had 11-DOC greater than 7.6 g/dl during MTP test and therefore CAI was excluded in all patients. MTP test was tolerated well by all individuals.

Conclusion: Central adrenal insufficiency was absent in 47 adults with Prader-Willi syndrome assessed by a multiple dose metyrapone test. This indicates that CAI is rare, or even absent, in adults with PWS. Based on these results, we recommend to perform MTP test instead of routinely prescribing HC stress dose in adults with PWS.