Central Adrenal Insufficiency Is Rare in Adults With Prader–Willi Syndrome

Abstract

Context Prader–Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension—already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity—or even mortality. Objective To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). Design Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). Setting Outpatient clinic. Patients or Other Participants Eighty-two adults with genetically confirmed PWS. Main Outcome Measure For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. Results Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. Conclusions Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS.

Missed Diagnoses and Health Problems in Adults With Prader-Willi Syndrome: Recommendations for Screening and Treatment

“…a Recommendation based on expert opinion and literature review ( 65–67 ). b Based on previously published data ( 68 ).…”

“…This is rare in adults with PWS ( 68 ). However, in cases of clinical signs of hypocortisolism, we recommend assessing the hypothalamic-pituitary-adrenal axis using the metyrapone test or, in the absence of contraindications, the insulin tolerance test (see Fig.…”

Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients

“…The most common pituitary hormone deficits are growth hormone (GH) deficiency (80% of patients), hypogonadism of mixed origin (90% of patients), and central hypothyroidism (20-40% of patients) [8][9][10]. A few cases of adrenal insufficiency have also been described, but the prevalence appears to be low [11,12]. Since obtaining marketing authorization (MA) in 2000, GH supplementation has been systematic in children with PWS, with treatment starting in the first year of life.…”

Hyponatremia in Children and Adults with Prader–Willi Syndrome: A Survey Involving Seven Countries

“…Among the hormonal deficits, hypogonadism is the most frequent in PWS, with expression in both sexes and at all ages [9] and sex hormone substitution could present a greater risk for hyponatremia in women [10]. In addition, central adrenal insufficiency is rare, about 1% in adults with PWS [11], but is known to induce hyponatremia.…”