ESPE Abstracts

Background: CHARGE syndrome (acronym for coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital hypoplasia, and ear abnormalities) is caused by a mutation in the CHD7 gene. CHARGE syndrome shares features with Prader-Willi syndrome, especially regarding hypothalamic-pituitary abnormalities. In Prader-Willi syndrome, central adrenal insufficiency (CAI) during stressful conditions has been described in a large number of patients. The presence of CAI in CHARGE syndrome has never been thoroughly studied, although unexpected mortality has been observed.

Objective and hypotheses: The aim of our study was to assess the presence of CAI in patients with CHARGE syndrome.

Method: Patients (ages between 20 months and 18 years) with genetically confirmed CHARGE syndrome were recruited from our national multidisciplinary outpatient clinic. To detect CAI, a low-dose ACTH test (LDAT) (0.5 μg/1.73 m² body surface area Synacthen®) was performed. Blood samples for determination of cortisol were taken at −15, 0, 30, and 60 minutes. A maximum cortisol concentration > 500 nmol/l excluded CAI. In case of suspected CAI, a glucagon test (0.05 – 0.1 mg glucagon per kg body weight, maximum 1 mg) was performed on a separate occasion. Blood samples for determination of cortisol were taken at baseline and then every 30 minutes during 3 consecutive hours. Cut-off levels to detect CAI were similar as in the LDAT.

Results: From 83 eligible patients, 27 were included in the study. In three patients, the LDAT could not be performed due to technical reasons, and 1 patient withdrew from the study. In total, 23 patients were tested (14 male, mean (SD) age 9.3 (5.0) years). Seven patients showed an insufficient maximum cortisol concentration in the LDAT (mean (SD) 425 (71) nmol/l), and underwent a glucagon test (1 patient underwent a standard dose ACTH test). Out of these seven patients, one patient was diagnosed with CAI (maximum cortisol concentration 415 nmol/l).

Conclusion: CAI is not a common feature in CHARGE syndrome. Further studies in a larger number of patients are required to confirm our findings.

Funding information: This work was supported by Fonds NutsOhra (grant number 1202-023).