Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment.
ABSTRACT 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.
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.
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 > or = 0.2).
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.
Article: Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia.[show abstract] [hide abstract]
ABSTRACT: The purpose of the study was to determine the prevalence of metabolic syndrome, growth hormone deficiency, and cardiovascular risk factors among adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without cranial irradiation. Follow-up was undertaken of 75 randomly selected long-term childhood ALL survivors. Testing included fasting insulin, glucose, lipids, and growth hormone (GH) releasing hormone plus arginine stimulation test. The prevalence of metabolic syndrome was compared with population norms from 1999-2002 National Health and Nutrition Examination Study (NHANES) data, and internally between those with and without past cranial irradiation and those with normal (>16.5 microg/L) versus insufficient (9-16.5 microg/L) versus deficient (<9 microg/L) peak GH secretion. The mean subject age was 30 years and the mean time since ALL diagnosis was 25 years. The prevalence of metabolic syndrome did not differ statistically (P = .87) between study subjects (16.6%) and same-age, same-sex population norms (17.5%). However, 60% of subjects treated with cranial irradiation, compared with 20% of those who were not, had 2 or more of the 5 components of metabolic syndrome. Untreated abnormally low GH was present in 64% of subjects overall and 85% of those who received past cranial irradiation. Cranial irradiation was strongly related to GH deficiency, and in turn lower insulin-like growth factor 1 (IGF-1), higher fasting insulin, abdominal obesity, and dyslipidemia, particularly in women. Hematologists who treat childhood ALL patients, and particularly those who provide primary care to adult survivors, should be aware of the potential for long-term GH deficiency and adverse cardiovascular and diabetes risk profiles as a consequence of leukemia treatment.Cancer 09/2006; 107(6):1303-12. · 4.77 Impact Factor
Article: Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH-deficient adult survivors of childhood-onset acute lymphoblastic leukemia.[show abstract] [hide abstract]
ABSTRACT: Survivors of childhood-onset (CO) acute lymphoblastic leukemia (ALL) treated with prophylactic cranial radiotherapy often exhibit GH deficiency (GHD), which is associated with increased prevalence of cardiovascular risk factors and cardiac dysfunction. The objective of the study was to evaluate the effect of GH replacement on cardiovascular risk factors and cardiac function in former CO ALL patients. Eighteen former CO ALL patients (aged 19-32 yr) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and with confirmed GHD were studied at baseline and after 12 (n = 18) and 24 months (n = 13) of GH treatment (median 0.5 mg/d). A group of 18 age- and sex-matched subjects served as controls. After 12 months of GH treatment, a significant decrease in serum leptin (P = 0.002), leptin per kilogram fat mass (FM) (P = 0.01), plasma glucose (P = 0.004), FM (P = 0.002), and hip (P = 0.04) and waist (P = 0.02) circumference and increased muscle mass (P = 0.004) were recorded in the patients. Before GH treatment six patients had a metabolic syndrome, but after 12 months only one had it and after 24 months none. After 24 months of GH treatment, an increase in left ventricular mass index (P = 0.06) and significant improvements in cardiac systolic function, measured as fractional shortening (P = 0.03) and ejection fraction (P = 0.03), were recorded. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome were recorded after 2 yr of GH replacement in former CO ALL patients with GHD. Long-term follow-up is highly warranted.Journal of Clinical Endocrinology & Metabolism 06/2006; 91(5):1872-5. · 6.50 Impact Factor