Introduction

Individuals with Prader-Willi syndrome (PWS) have deficiencies of several hypothalamic-pituitary axes. Studies have reported differing prevalences of central adrenal insufficiency (CAI) in PWS, ranging from 0% to 60%. If CAI is present, timely diagnosis and treatment is needed 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 with PWS receive standard hydrocortisone (HC) stress dose during physical and/or psychological stress, which increases the risk of obesity, hypertension, osteoporosis and diabetes. 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 45 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 8h00. At 8h00 on day two, 11-deoxycortisol (11-DOC) levels were determined after 8 hours fasting. Levels of 11-DOC greater than 7.6  g/dL (230 nmol/L) were classified as adrenal sufficiency.

Results

Mean age of participants was 31 y. 17 had been using growth hormone since childhood. Male/female ratio was 28/17. 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 45 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 patients.

Conclusion

CAI was absent in 45 adults with PWS as assessed by 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.