The increased cerebrovascular mortality may be due to GH deficiency, or to long-term lack or inadequacy of substitution for other pituitary hormones. The observations that an early onset of pituitary insufficiency and female sex are predictors for a high risk for cerebrovascular mortality merit particular attention when treating this group of patients.

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...

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.