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Children Experience Cognitive Decline Despite Reversal of Brain Atrophy One Year After Resolution of Cushing Syndrome

Pediatric and Reproductive Endocrinology Branch (D.P.M., M.F.K., S.L.M., E.A.W., S.H., E.R., G.P.C.) and Section on Endocrinology of Genetics (C.A.S.), Developmental Endocrinology Branch, National Institute of Child Health and Human Development; the Warren Grant Magnuson Clinical Center (D.P.M.); and the Child Psychiatry Branch (A.C.V., J.N.G.), National Institute of Mental Health, Bethesda, Maryland 20892-1932

Address all correspondence and requests for reprints to: Deborah P. Merke, M.D., National Institutes of Health, Building 10, Room 13S260, 10 Center Drive, MSC 1932, Bethesda, Maryland 20892-1932. E-mail: dmerke{at}nih.gov.

Adults with Cushing syndrome frequently develop brain atrophy, memory impairment, and depression, with partial to complete resolution after cure. The effect of excess glucocorticoid exposure on the brain of children has not been systematically studied. Eleven children (six girls, five boys; ages, 8–16 yr) with endogenous Cushing syndrome seen at the National Institutes of Health Clinical Center from 1999–2000 and 10 healthy age- and sex-matched control subjects were studied. Cognitive and psychological evaluations and magnetic resonance imaging of the brain were done before and 1 yr after cure for patients with Cushing syndrome and once for controls. The estimated duration of Cushing syndrome was 4.4 ± 1.2 yr. When compared with control subjects, children with Cushing syndrome had significantly smaller cerebral volumes (P < 0.001), larger ventricles (P = 0.02), and smaller amygdala (P = 0.004). At baseline, there were no significant differences in IQ between the two groups, and no psychopathology was identified. Despite reversal of cerebral atrophy 1 yr after surgical cure (total cerebral volume, 947 ± 94 vs.1050 ± 74 ml, P < 0.001; ventricular volume, 21.4 ± 12.5 vs. 14.5 ± 11.6 ml, P < 0.001), children with Cushing syndrome experienced a significant (P < 0.05) decline in Wechsler IQ scores (Full Scale, 112 ± 19 vs. 98 ± 14) and a decline in school performance, without any associated psychopathology. The effect of glucocorticoid excess on the brain of children appears to be different from adults. Despite rapid reversibility of cerebral atrophy, children experience a significant decline in cognitive function 1 yr after correction of hypercortisolism.

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