Prader-Willi syndrome: A primer for clinicians

The advent of sensitive genetic testing modalities for the diagnosis of Prader-Willi syndrome has helped to define not only the phenotypic features of the syndrome associated with the various genotypes but also to anticipate clinical and psychological problems that occur at each stage during the life span. With advances in hormone replacement therapy, particularly growth hormone children born in circumstances where therapy is available are expected to have an improved quality of life as compared to those born prior to growth hormone

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

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.</jats:p