Monica T Y Wong1, Conny M A van Ravenswaaij-Arts2, Craig F Munns3, Peter Hsu4, Sam Mehr4, Gianni Bocca5. 1. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: t.y.wong@umcg.nl. 2. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Department of Endocrinology, The Children's Hospital at Westmead, Sydney, Australia. 4. Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia. 5. Department of Pediatrics, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: CAI was not common in our cohorts, and routine testing of adrenal function in children with CHARGE syndrome is not indicated.
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: CAI was not common in our cohorts, and routine testing of adrenal function in children with CHARGE syndrome is not indicated.
Authors: Christa M de Geus; Rolien H Free; Berit M Verbist; Deborah A Sival; Kim D Blake; Linda C Meiners; Conny M A van Ravenswaaij-Arts Journal: Am J Med Genet C Semin Med Genet Date: 2017-11-23 Impact factor: 3.908