Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving longterm survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified.The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19 -32 yr at the time of study) treated with CRT (median 24 Gy, 18 -30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRHarginine test, and patients with a peak GH 3.9 g/liter or greater were further investigated with an additional insulin tolerance test.Significantly higher plasma levels of insulin (P ‫؍‬ 0.002), blood glucose (P ‫؍‬ 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P < 0.05) were recorded among the ALL patients, compared with controls. Furthermore, the serum levels of high-density lipoprotein cholesterol (P ‫؍‬ 0.03) and Apo A1 (P ‫؍‬ 0.005) were significantly lower among the patients. Compared with controls, the patients had higher body mass index and waist to hip ratio, and body composition measured with dual-energy x-ray absorptiometry showed significantly higher fat mass and lower lean mass (P < 0.001). Forty of 44 ALL patients (91%) were considered GH deficient according to the insulin tolerance test and/or the GHRHarginine test, and the rest were considered GH insufficient.In patients, peak GH during GHRH-arginine was significantly negatively correlated to total body fat mass measured with dual-energy x-ray absorptiometry (r ‫؍‬ ؊0.48, P ‫؍‬ 0.001), waist to hip ratio (r ‫؍‬ ؊0.32, P ‫؍‬ 0.03), plasma insulin (r ‫؍‬ ؊0.49, P ‫؍‬ 0.001), and leptin (r ‫؍‬ ؊0.46, P ‫؍‬ 0.002). Moreover, a significantly positive correlation was recorded with highdensity lipoprotein cholesterol (r ‫؍‬ 0.38, P ‫؍‬ 0.012). Using Doppler echocardiography, a marked reduction in cardiac dimensions and performance (ejection fraction P < 0.001 and fractional shortening P ‫؍‬ 0.01), compared with controls, was recorded.In conclusion, at a median 17 yr after treatment with CRT and chemotherapy in former childhood ALL patients, a significant increase in cardiovascul...

These guidelines can be applied in clinical work and indicate future research needs.

47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from "near-normal" to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under-diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age-specific recommendations for medical management. © 2013 Wiley Periodicals, Inc.

Because the study was initiated before 1 July 2005, the protocol was not registered in a registry.

Summary OBJECTIVE  Adult survivors of childhood acute lymphoblastic leukaemia (ALL) often exhibit GH deficiency (GHD), due to prophylactic cranial radiotherapy (CRT). It is not known whether the observed risk for adiposity in these patients is associated with impaired insulin sensitivity and whether the insulin sensitivity is affected by GH replacement therapy. SUBJECTS AND DESIGN  Eleven patients with GHD (median age 29 years), previously given prophylactic CRT for ALL, and 11 sex‐, age‐ and body mass index (BMI)‐matched controls were investigated with bioimpedance analysis (BIA) and analysis of serum leptin, serum free fatty acids (FFA) and serum insulin. Insulin sensitivity was measured by a euglycaemic–hyperinsulinaemic clamp technique (IS‐clamp). Moreover, the effects of 12 months of individually titrated GH treatment (median dose 0·5 mg/day) on these parameters were investigated. RESULTS  At baseline, the patients had lower fat free mass (FFM) (P = 0·003), higher percentage fat mass (FM) (P = 0·05), serum insulin (P = 0·02) and serum leptin/kg FM (P = 0·01) than controls. The patients had a tendency towards impaired IS‐clamp (P = 0·06), which disappeared after correction for body composition (IS‐clamp/kg FFM; P > 0·5). In the patients, time since CRT was positively correlated with percentage FM (r = 0·70, P = 0·02), and there was an independent negative association between serum FFA and IS‐clamp (P = 0·05). Twelve months of GH treatment increased serum IGF‐I (P = 0·003) and FFM (P = 0·02) and decreased percentage FM (P = 0·03), but no significant changes were seen in serum leptin/kg FM, serum FFA, FFA‐clamp, serum insulin or IS‐clamp (all, P ≥ 0·2). CONCLUSIONS  Young adult survivors of childhood ALL with GHD had increased fat mass, hyperleptinaemia and impaired insulin sensitivity, which could be a consequence of radiation‐induced impairment of GH secretion or mediated by other hypothalamic dysfunctions, such as leptin resistance or other unknown factors, affected by CRT. Twelve months of individualized GH replacement therapy led to positive effects on body composition, but the hyperleptinaemia, hyperinsulinaemia and the impaired insulin sensitivity remained unchanged.