Central Adrenal Insufficiency Is Not a Common Feature in CHARGE Syndrome: A Cross-Sectional Study in 2 Cohorts.
To evaluate whether central adrenal insufficiency (CAI) is present in CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear abnormalities, including deafness) syndrome, a complex malformation disorder that includes central endocrine dysfunction.



Two cross-sectional studies were performed in Dutch (September 2013-February 2015) and Australian (January 2012-January 2014) CHARGE syndrome clinics. Twenty-seven Dutch and 19 Australian patients (aged 16 months-18 years) with genetically confirmed CHARGE syndrome were included. The low-dose adrenocorticotropin (ACTH) test was used to assess CAI in the Dutch cohort. A peak cortisol response less than 18.1 μg/dL (500 nmol/L) was suspected for CAI, and a glucagon stimulation test was performed for confirmation. Australian patients were screened by single measurements of ACTH and cortisol levels. If adrenal dysfunction was suspected, a standard-dose ACTH test was performed.



The low-dose ACTH test was performed in 23 patients (median age 8.4 [1.9-16.9] years). Seven patients showed an insufficient maximum cortisol level (10.3-17.6 μg/dL, 285-485 nmol/L), but CAI was confirmed by glucagon stimulation test in only 1 patient (maximum cortisol level 15.0 μg/dL, 415 nmol/L). In the Australian cohort, 15 patients (median age 9.1 [1.3-17.8] years) were screened, and none had CAI.



CAI was not common in our cohorts, and routine testing of adrenal function in children with CHARGE syndrome is not indicated.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: t.y.wong@umcg.nl.
Monica T Y
MT
Wong
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Conny M A
CM
van Ravenswaaij-Arts
Department of Endocrinology, The Children's Hospital at Westmead, Sydney, Australia.
Craig F
CF
Munns
Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia.
Peter
P
Hsu
Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia.
Sam
S
Mehr
Department of Pediatrics, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Gianni
G
Bocca
D000293:Adolescent; D000309:Adrenal Insufficiency / Q000453:epidemiology / Q000209:etiology*; D058747:CHARGE Syndrome / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male
glucagon stimulation test; low-dose adrenocorticotropin test; mortality