Long-term cortisol levels in hair of children and adolescents with Prader-Willi Syndrome.

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.