cosyntropin and Prader-Willi-Syndrome

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.. The objective of the study was to further explore the HPA axis in PWS by use of routine tests.. 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.. The study was conducted at university hospitals in Denmark and Sweden.. Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study.. A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response.. 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.. In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Child, Preschool; Cosyntropin; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immunoassay; Infant; Insulin; Male; Middle Aged; Pituitary Function Tests; Pituitary-Adrenal System; Prader-Willi Syndrome

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Cosyntropin; Humans; Hydrocortisone; Insulin; Obesity; Pituitary-Adrenal System; Prader-Willi Syndrome; Prevalence; Retrospective Studies; Scotland

It has been postulated that central adrenal insufficiency (CAI), resulting from hypothalamic dysfunction, may contribute to the increased unexplained death rates in Prader Willi syndrome (PWS). A study using the overnight metyrapone test reported a 60% prevalence of CAI in children with PWS. We used a low-dose Synacthen test to screen for CAI in children with PWS.. We studied 41 children with genetic diagnosis of PWS [20 males; mean age, 7.68 (±5.23) yr] in five pediatric endocrinology centers in Australasia. All participants were randomly selected, and none had a history of Addisonian crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving GH, and four were receiving T4. Their mean body mass index z-score was +1.48 (±1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv administration of 1 μg Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal.. The mean baseline ACTH and cortisol were 15 (±14) ng/liter and 223 (±116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (±114) nmol/liter, and the average increase from baseline was 201%.. Our result suggests that CAI is rare in children with PWS.

Topics: Adrenocorticotropic Hormone; Australasia; Body Mass Index; Child; Child, Preschool; Cosyntropin; Female; Gonadal Steroid Hormones; Hormones; Humans; Hydrocortisone; Male; Prader-Willi Syndrome; Reference Values; Thyroxine