Normal Cortisol Response to High-Dose Synacthen and Insulin Tolerance Test in Children and Adults with Prader-Willi Syndrome

摘要

Context: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested.Objective: The objective of the study was to further explore the HPA axis in PWS by use of routine tests.Design: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness.Setting: The study was conducted at university hospitals in Denmark and Sweden.Patients: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study.Main Outcome Measures: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response.Results: Fifty-seven PWS patients (median age 22 yr, total range 0.5–48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474–1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16–36) yr] examined with the ITT had a median peak s-cortisol of 668 (502–822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter.Conclusion: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.