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

L Damen,S.H Donze,L.N Grootjen,A.C.S Hokken-Koelega

doi:10.1016/j.psyneuen.2021.105335

Abstract

ContextPrader-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. ObjectiveTo investigate long-term cortisol levels in hair and CAR in children with PWS. DesignCross-sectional study. Patients41 children with PWS. SettingDutch PWS Reference Center. Main outcome measuresHCC and salivary cortisol measured by LCMS. ResultsMedian (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. ConclusionsHCC 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.

Highlights

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the lack of expression of paternally inherited imprinted genes on chromo some 15q11-q13, due to a paternal deletion, maternal uniparental dis omy, imprinting center defect (ICD) or translocation (Goldstone et al, 2008; Cassidy and Driscoll, 2009)
We subsequently investigated the relation between Hair cortisol concentration (HCC) and Cortisol awakening response (CAR)
This study in 41 children and adolescents with PWS shows that HCC is normal in the majority (86.8%) of children and adolescents with PWS, which implies a normal cortisol production during daily life

Summary

Introduction

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the lack of expression of paternally inherited imprinted genes on chromo some 15q11-q13, due to a paternal deletion, maternal uniparental dis omy (mUPD), imprinting center defect (ICD) or translocation (Goldstone et al, 2008; Cassidy and Driscoll, 2009). PWS is characterized by muscular hypotonia, abnormal body composition, developmental delay, behavioral problems, hyperphagia and endocrinopathies like growth hormone deficiency, hypothyroidism and hypogonadism (Holm et al, 1993; Cassidy, 1997; Eiholzer et al, 2000; Goldstone et al, 2008). Cortisol is produced by the adrenal cortex under the influence of (pituitary) adrenocorticotropic hormone (ACTH). Cortisol can be measured in serum, saliva, urine and hair. A disadvantage of serum and saliva measurements is that they only provide a measurement of the cortisol concentration at a single point in time and are subject to major physiological circadian fluctua tions, with a peak plasma cortisol level in the early morning (in healthy individuals) and a gradual decrease thereafter

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