RESUMEN
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.
Asunto(s)
Encéfalo/patología , Cognición , Síndrome de Cushing/patología , Síndrome de Cushing/psicología , Adolescente , Atrofia , Índice de Masa Corporal , Niño , Femenino , Humanos , Inteligencia , Imagen por Resonancia Magnética , MasculinoRESUMEN
Classic congenital hyperplasia (CAH) is characterized by impaired adrenocortical function with a decrease in cortisol and aldosterone secretion and an increase in androgen secretion. Adrenomedullary function is also compromised due to developmental defects in the formation of the adrenal medulla, leading to decreased production of epinephrine. To examine the response to a natural stressful stimulus in patients with classic CAH, we studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with CAH and nine healthy controls matched for gender, age, and percent body fat. The same relative workload was applied, based on individual maximal aerobic capacity, and all patients received their usual glucocorticoid and mineralocorticoid replacement. When compared with their normal counterparts, patients with CAH had significantly lower epinephrine levels both at baseline and at peak exercise (P < 0.01), whereas norepinephrine levels did not differ. Blood glucose concentrations were similar at baseline, but the normal exercise-induced rise observed in the healthy controls was significantly blunted in the CAH patients (P < 0.01). Peak heart rate was also lower in CAH patients than healthy controls (P < 0.05). As expected, the normal exercise-induced increase in cortisol was not observed in patients with CAH. No significant differences were found in serum levels of insulin, glucagon, GH, lactate and free fatty acids, blood pressure, or ability to sustain exercise between the two groups. Patients with CAH replaced with glucocorticoids have decreased adrenomedullary reserve and impaired exercise-induced changes in glucose but normal short-term high-intensity exercise performance. Whether the combination of epinephrine and cortisol deficiency poses a risk for hypoglycemia and/or decreased endurance during long-term physical stress has to be determined.