Endocrine sequelae of cancer therapy in childhood.

New treatments for neoplastic diseases of childhood have significantly increased patients' long-term survival and the importance of recognizing and correcting late complications of medical therapy. In this review, we examine both central nervous system (CNS) and non-CNS-related endocrine morbidities associated with chemotherapy and radiation therapy of childhood cancer. These include effects on growth, puberty, fertility, thyroid and adrenal function which may present many years after the successful treatment of underlying disease.

Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol.

Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/- 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

Leptin binding activity (LBA) in plasma of nondiabetic and diabetic adolescents and obese children: relation to auxologic and hormonal data.

Leptin circulates in serum bound to high molecular weight proteins. Hypothesizing that leptin binding proteins may regulate the functional efficiency of leptin, we characterized auxologic and hormonal factors that influence leptin binding in three disparate groups: normal adolescents, obese children, and teenagers with type I diabetes mellitus (IDDM). Specific leptin binding activity (sLBA) was assessed by column chromatography after incubation of serum with 125I-leptin in the presence and absence of excess unlabeled leptin. Mean sLBA was 17.0 +/- 7% (SD) in the healthy adolescents (n=41), 6.6 +/-4.3% in the obese children (n=26), and 14.9 +/-7.3% in the diabetic teenagers (n=17). At any value of sLBA, obese children had higher serum leptin levels than non-obese adolescents or diabetic teenagers, consistent with "leptin resistance" in the obese group. sLBA was higher in males than in females only in those with diabetes (18.6 +/- 7.3 vs 10.9 +/- 5.1%, p<0.05). sLBA correlated inversely with serum insulin-like growth factor-I values in the normal group (r= -0.45, p<0.01) and with insulin in the obese children (r= -0.53, p<0.01). There was no correlation between sLBA or serum leptin values and HbA1c, in the diabetic group. The serum leptin concentration was the principal determinant explaining the total variability of sLBA in all three cohorts. However, body mass index (BMI = weight/ height2) accounted for more of the total variability of percent specific binding in the healthy adolescents than in the other groups. We conclude that sLBA reflects circulating leptin levels, body composition, and hormonal milieu. Thus, in addition to leptin, qualitative and quantitative characteristics of leptin binding may play a physiological role in the regulation of appetite and in the "leptin resistance" of obesity.

Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature.

OBJECTIVES: Normal short stature (NSS), defined as height below the 5th percentile for age and sex norms that is not due to illness, hormonal deficiency, or part of a dysmorphic syndrome, has been thought to have a deleterious effect on psychosocial functioning based on observations of referred populations. Recent studies of nonreferred children with NSS, however, have demonstrated normal function. This study directly compared the psychosocial functioning of referred children with NSS, nonreferred children with NSS, and children with normal stature. STUDY DESIGN: Participants, 90 children (46 boys, 44 girls) between 6 and 12 years of age (mean, 9. 6 years), were administered intelligence and achievement tests. Parents and teachers assessed adaptive and problem behaviors. Family adaptability and cohesiveness were measured. RESULTS: Intelligence and achievement for referred and nonreferred children with NSS were average. Referred children with NSS were reported to have more externalizing behavior problems and poorer social skills than nonreferred children with NSS and children in the control group. Family adaptability and cohesiveness were comparable across groups. CONCLUSIONS: Children with NSS have normal psychosocial function, and results suggest that externalizing behavior problems, attention problems, and poor social skills in children referred to clinics for NSS are inappropriately attributed to short stature.