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

Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1932, USA.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 05/2005; 90(5):2531-6. DOI: 10.1210/jc.2004-2488
Source: PubMed


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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    • "Notably, studies on hippocampal cell cultures showed that supraphysiological doses of glucocorticoids lead to a reversible phase of atrophy of the apical dendrites of pyramidal neurons [24]. In addition, glucocorticoids have been shown to increase the synaptic accumulation of glutamate and to stimulate the N-methyl-D-aspartate (NDMA) receptors with a subsequent increase in intracellular cytosolic Ca + in postsynaptic neurons, which activate several processes leading to neuron cell death [19] [22]. Of note, the partial reversibility of brain atrophy after a return to eucortisolism would indicate that the abovediscussed MRI abnormalities are not exclusively related to neuronal death. "
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    • "The hippocampus is the most studied brain structure showing neuronal degeneration associated to stress and high glucocorticoid levels [4], followed by the prefrontal cortex as observed in Cushing's disease, major depression and PTSD [1;17;18]. Smaller amygdaloid nucleus [19] and an overall brain atrophy were also reported by magnetic resonance imaging in Cushing's patients [5;17]. Another clinical study showed that the reduced volume of the cingulate gyrus correlated to an increase in plasma adrenocorticotropic hormone levels in humans [20]. "
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