ABSTRACT
CONTEXT: Prader-Willi syndrome (PWS) is characterized by hypothalamic dysfunction. In children with PWS, stress-induced central adrenal insufficiency (CAI) has been described, however, daily life cortisol production may be normal. Hair cortisol concentration (HCC) is a marker of long-term systemic cortisol production. Cortisol awakening response (CAR) is the increase in cortisol level after awakening. A negative CAR might suggest hypothalamic-pituitary-adrenal (HPA)-axis reactivity problems. Little is known about HCC and CAR in children with PWS. OBJECTIVE: To investigate long-term cortisol levels in hair and CAR in children with PWS. DESIGN: Cross-sectional study. PATIENTS: 41 children with PWS. SETTING: Dutch PWS Reference Center. MAIN OUTCOME MEASURES: HCC and salivary cortisol measured by LCMS. RESULTS: Median (IQR) HCC was 1.90 (1.02-3.30) pg/mg at a median (IQR) age of 14.5 (8.20-19.0) years, with median HCC in age-matched references being 2.63 pg/mg. Five patients (13.2%) had HCC < 2.5th percentile for age and these patients had a repeatedly negative CAR. Median HCC was significantly lower in patients with negative CAR than in patients with normal CAR (1.00 (0.22-1.59) vs. 2.25 (1.47-3.26) pg/mg, p = 0.007). One patient had both HCC < 2.5th percentile and repeatedly low morning salivary cortisol levels and negative CAR, and was diagnosed with adrenal insufficiency by overnight metyrapone test. CONCLUSIONS: HCC were normal in the majority of children with PWS. Our data suggest that children with HCC < 2.5th percentile and (repeatedly) negative CAR might possibly have adrenal insufficiency or delayed HPA-axis responsiveness.
