Tricuspid Valve Endocarditis in Four Patients with Unrepaired Restrictive Perimembranous Ventricular Septal Defects.

Congenital heart disease (CHD) is the most common predisposing factor for pediatric infective endocarditis (IE). Although patients with unrepaired ventricular septal defects (VSDs) are at greater risk of IE than those without CHD, the American Heart Association (AHA) considers VSDs to be relatively low risk and therefore does not recommend antibiotic prophylaxis against IE. Even among patients with VSDs who develop IE, current AHA and European Society for Cardiology (ESC) guidelines do not recommend surgical VSD closure, despite the potential for a second IE event. We present a case series of four children with small, restrictive, perimembranous VSDs who developed tricuspid valve (TV) IE. All four experienced delayed diagnosis and secondary complications, including three with septic pulmonary emboli. All four patients ultimately underwent surgical VSD closure. These cases highlight the importance of recognizing IE as a possible cause of prolonged fever in children, even among those with even 'low-risk' CHD. The cases also draw attention to the potential benefits of VSD closure in patients who develop IE.

Amygdala function in adolescents with congenital adrenal hyperplasia: a model for the study of early steroid abnormalities.

Early disruption of steroids affects the development of mammalian neural circuits underlying affective processes. In humans, patients with classic congenital adrenal hyperplasia (CAH) can serve as a natural model to study early hormonal alterations on functional brain development. CAH is characterized by congenital glucocorticoid insufficiency, leading to altered hypothalamic-pituitary-adrenal (HPA) function, and hyperandrogenism. Using fMRI, we compared fourteen adolescents with CAH to 14 healthy controls on amygdala response to a face viewing task. In response to negative facial emotions, CAH females activated the amygdala significantly more than healthy females, whereas CAH males did not differ from control males. Furthermore, females with CAH showed a similar pattern of amygdala activation to control males, suggesting virilized amygdala function in females with CAH. These findings suggest a prominent effect of early hyperandrogenism on the development and function of the amygdala in females with CAH, whereas no effects were detected in males with CAH. This study provides data that can be further tested in a model of the neurobiological mechanisms underlying early androgen organizational effects on amygdala function.

Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome.

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.

Stress dose of hydrocortisone is not beneficial in patients with classic congenital adrenal hyperplasia undergoing short-term, high-intensity exercise.

Classic congenital adrenal hyperplasia (CAH) is associated with impaired function of the adrenal cortex and medulla leading to decreased production of cortisol and epinephrine. As a result, the normal exercise-induced rise in blood glucose is markedly blunted in such individuals. We examined whether an extra dose of hydrocortisone, similar to that given during other forms of physical stress such as intercurrent illness, would normalize blood glucose levels during exercise in patients with CAH. We studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with classic CAH. Patients were assigned to receive either an additional morning dose of hydrocortisone or placebo, in addition to their usual glucocorticoid and mineralocorticoid replacement in a randomized, double-blind, crossover design 1 h before exercising. Although plasma cortisol levels approximately doubled after administration of the additional hydrocortisone dose compared with the usual single dose, fasting and exercise-induced blood glucose levels did not differ. In addition, no differences were observed in the serum concentrations of the glucose-modulating hormones epinephrine, insulin, glucagon, and GH and of the metabolic parameters lactate and free fatty acids. Although maximal heart rate was slightly higher after stress dosing (193 +/- 3 vs. 191 +/- 3 beats/min, mean +/- sem, P < 0.05), this did not affect exercise performance or perceived exertion. We conclude that patients with classic CAH do not benefit from additional hydrocortisone during short-term, high-intensity exercise. Although this has not been tested with long-term exercise, a high degree of caution should be used when considering the frequent use of additional hydrocortisone administration with exercise, given the adverse side effects of glucocorticoid excess.