BACKGROUND Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. METHODS We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. RESULTS We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein–coupled receptor, was overexpressed in patients’ pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone–producing cells. CONCLUSIONS We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.)

Children's reports of binge eating and dieting were salient predictors of gains in fat mass during middle childhood among children at high risk for adult obesity. Interventions targeting disordered eating behaviors may be useful in preventing excessive fat gain in this high-risk group.

OBJECTIVE-To investigate the relationship between loss of control over eating, adiposity, and psychological distress in a non-treatment sample of overweight children.METHOD-Based on self-reports of eating episodes, 112 overweight children, 6-10 y, were categorized using the Questionnaire of Eating and Weight Patterns -Adolescent Version into those describing episodes of loss of control over eating (LC), and those with no loss of control (NoLC). Groups were compared on measures of adiposity, dieting and eating behavior, and associated psychological distress.RESULTS-LC children (33.1%) were heavier and had greater amounts of body fat than NoLC children. They also had higher anxiety, more depressive symptoms, and more body dissatisfaction. 5.3% met questionnaire criteria for BED. Episodes of loss of control occurred infrequently, were often contextual, and involved usual meal foods. DISCUSSION-As in adults, overweight children reporting loss of control over eating have greater severity of obesity and more psychological distress than those with no such symptoms. It remains unknown whether children who endorse loss of control over eating before adolescence will be those who develop the greatest difficulties with binge eating or obesity in adulthood. KeywordsBinge eating; obesity; child; race; psychopathology Binge eating is a frequent behavior in overweight adults ( Loro & Orleans, 1981;Gormally, Black, Daston & Rardin, 1982;Marcus, Wing & Lamparski, 1985;Spitzer et al, 1992;Fairburn & Wilson, 1993;Grisset & Fitzgibbon, 1996;Robertson & Palmer, 1997), and is Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript defined by the consumption of large amounts of food associated with a feeling of loss of control over eating (Fairburn & Wilson, 1993). A smaller proportion of individuals reporting binge eating meet criteria for binge eating disorder (BED), a research diagnostic category of the DSM IV that is characterized by recurrent binge-eating episodes associated with marked distress, but without inappropriate compensatory behaviors. The prevalence of BED in obese adults seeking weight loss treatment may be as high as 20% to 30% (Spitzer et al., 1992 while rates of BED in community samples have been estimated at somewhat less than 3% (Yanovski, 1999).In adults, binge eating is often associated with obesity (Telch, Agras & Rossiter, 1988;Smith, Marcus, Lewis, Fitzgibbon & Schreiner, 1998) and other disturbed eating behaviors. Besides having less ability to control eating behavior (Grisset & Fitzgibbon, 1996;Wadden, Foster, Letizia & Wilk, 1993;Kuehnel & Wadden, 1994), obese adults reporting binge eating also have greater concerns with body shape and weight (Marcus, Smith, Santilli, Kaye, 1992;Spitzer et al., 1993;Wilson, Nonas & Rosenblum, 1993), report an earlier onset of obesity and dieting, and describe a higher percentage of their lifetimes spent on a diet than non-binge eating obese individuals (Brody, Walsh & Devlin, 1994). Several studies have shown that obese adult binge eaters also report...

Congenital adrenal hyperplasia compromises both the development and the functioning of the adrenomedullary system.

AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. It is frequently associated with atypical CS and increased 17OHS; UFCs and other measures of adrenocortical activity can be misleadingly normal.

According to adolescent and parent reports, overweight is associated with poorer QOL in adolescence, regardless of race; however, compared with overweight white adolescents, blacks report less impairment in QOL. Future research is required to determine whether differences in QOL are predictive of treatment success.

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.

Research Methods and Procedures:We associated selfreport of depression, trait anxiety, and weight-related distress (body size dissatisfaction and weight-related peer teasing after controlling for the effects of weight) in 164 children (black 35%; age 11.9 Ϯ 2.5 years; girls 51%) who were overweight or at-high-risk-for-overweight and were not seeking weight loss. Results: Overall, heavier children reported more psychological and weight-related distress. Black children reported more anxiety and body size dissatisfaction than white children, despite equivalent weights. However, psychological distress was not significantly associated with weight in white children. Girls reported more weight-related distress than boys. Depression was associated with weight-related teasing in all predictive models, except in the model using only black subjects. Trait anxiety was associated with report of peer teasing when using all subjects. Depression was also significantly associated with children's report of body size dissatisfaction in models using all subjects, only girls, or white subjects, but not in analyses using only boys or black subjects. For boys peer teasing was associated with body size dissatisfaction. In models including only black children, depression and trait anxiety were not significantly associated with either report of peer teasing or body size dissatisfaction. Discussion: Regardless of race or sex, increasing weight is associated with emotional and weight-related distress in children. However, associations of psychological status, weight, and weight-related distress differ for girls and boys, and for black and white children.