Introduction: Individuals with Prader-Willi syndrome (PWS) suffer from hyperphagia, hypotonia and hypothalamic dysfunction, leading to a variety of pituitary hormone deficiencies. Central adrenal insufficiency (CAI) has been reported in PWS, while each of these studies used different testing modalities and cut-off values. Therefore, reported prevalence of CAI ranges from 0% to 60%. It has been speculated that CAI might be responsible, at least in part, for the high mortality (3%) in patients with PWS. If CAI is present, timely diagnosis and treatment is needed in order to prevent avoidable mortality. There are no guidelines on the appropriate evaluation and management of CAI in adults with PWS. In our center, many adult patients with PWS receive standard hydrocortisone (HC) treatment around physical and/or psychological periods of 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 real prevalence of CAI in order to prevent both under- and overtreatment with HC.
Methods: We performed multiple dose metyrapone (MTP) test in 42 patients and insulin tolerance test (ITT) in 9 patients. When levels of 11-DOC during MTP were greater than 230 nmol/L (7.6 g/dL) or levels of cortisol during ITT were greater than 500 nmol/L (18.1 μg/dL), adrenal insufficiency was excluded.
Results: 51 adult subjects (31 males and 20 females), median (range) age 29.2 (18.9 58.3) yrs, with genetically confirmed PWS, participated in the study. 22 subjects (43%) were using GH treatment since childhood. Using the MTP or ITT, CAI was excluded in all subjects. Even patients with a low baseline cortisol level (lowest: 119.0 nmol/L) appeared to have a normal MTP/ITT test result. MTP test/ITT were tolerated well by all individuals. Additional revision of medical files of all PWS adults visiting our ternary referral center (n = 120) revealed that none of the patients who underwent surgery without peri-operative hydrocortisone treatment had suffered complications due to hypocortisolism.
Conclusion: Central adrenal insufficiency appeared to be absent in all 51 adults with Prader-Willi syndrome tested by multiple dose metyrapone test or an insulin tolerance test. This indicates that CAI is rare in adults with PWS. Based on these results, we recommend performing a MTP or ITT test before prescribing hydrocortisone medication during periods of psychological or physical stress in all adults with PWS.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology