A novel variant of growth hormone (GH) insufficiencyfollowing low dose cranial irradiation

Crowne, Elizabeth; Moore, Clare; Wallace, W. Hamish B.; Ogilvy-Stuart, Amanda; Addison, G. M.; Morris‐Jones, P. H.; Shalet, Stephen M

doi:10.1111/j.1365-2265.1992.tb02903.x

Cited by 72 publications

(40 citation statements)

References 23 publications

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“…We did not measure growth hormone secretion in our patients. However, since growth hormone insufficiency (neurosecretory dysfunction) after cranial irradiation in the context of an ALL therapy has already been demonstrated by several investigators [23], this can also be assumed in our irradiated patients. Insufficient growth hormone secretion would explain two observations made in our irradiated patients: it alters the patients’ body composition, which in turn may influence their physical activity; and it can lead to a decrease in RMR as recently reported in patients with growth hormone insufficiency after discontinuation of growth hormone therapy [24].…”

Section: Discussionmentioning

confidence: 99%

Energy Expenditure, Energy Intake and Prevalence of Obesity after Therapy for Acute Lymphoblastic Leukemia during Childhood

et al. 2000

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Objectives: To investigate the prevalence and potential risk factors of obesity after therapy for childhood acute lymphoblastic leukemia (ALL). Study Design: 39 ALL patients (age 10.7–20.5 years) who were in first remission for 3.4–14.6 years after standardized treatment with chemotherapy plus cranial irradiation (n = 25) or with chemotherapy alone (n = 14) were examined. After fasting overnight, the following parameters were investigated: body mass index (BMI) of patients and their parents; patients’ BMI before ALL therapy; serum free thyroxin, growth hormone-dependent factors, estradiol, testosterone, cortisol, leptin and c-peptide; fat-free mass (bioelectrical impedance); resting metabolic rate (RMR, indirect calorimetry); caloric intake (24-hour recall); and physical activity (questionnaire). RMR data were applied to the fat-free mass and compared with 83 controls. Results: The prevalence of obesity (criterion: BMI > 2 SDS) was significantly (p < 0.05) higher after ALL therapy (38%; irradiated patients 48%, non-irradiated patients 21%) than before therapy (3%). Compared to non-irradiated patients, irradiated patients had significantly lower RMRs (–1.07 ± 0.24 vs. –0.32 ± 0.21 SDS; p < 0.05), reduced physical activity levels (1.41 ± 0.03 vs. 1.52 ± 0.03; p < 0.05), and lower concentrations of insulin-like growth factor-binding protein-3 (–0.65 ± 0.17 vs. 0.25 ± 0.33 SDS; p < 0.05) and of free thyroxin (1.17 ± 0.06 vs. 1.38 ± 0.08 ng/dl; p < 0.05). Caloric intake was adequate. Conclusions: After ALL during childhood, patients face a higher risk of obesity. In the cranially irradiated patients, the likely causes are low physical activity, RMRs and hormonal insufficiency.

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Section: Discussionmentioning

confidence: 99%

Energy Expenditure, Energy Intake and Prevalence of Obesity after Therapy for Acute Lymphoblastic Leukemia during Childhood

et al. 2000

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“…There is, however, general agreement that cranial XRT with 24–25 Gy is a potent cause of GH insufficiency. The 18-Gy data are more contentious in that Crowne et al [19] showed a quantitative reduction in GH secretion which was confined to the pubertal phase of childhood, associated with a disturbance in the periodicity of GH secretion. Lannering et al [20] confirmed the reduction in GH secretion during puberty, but observed that, in addition, it was present during prepubertal life, whilst, at the same time, they observed no qualitative abnormality in the pattern of GH secretion at any time.…”

Section: Cranial Irradiation and Chemotherapymentioning

confidence: 99%

Growth and Growth Hormone Status following Treatment for Childhood Leukaemia

Shalet¹,

Brennan²

1998

Horm Res Paediatr

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The exact contribution of growth hormone (GH) deficiency to the adverse growth outcome, in those receiving cranial irradiation (18–24 Gy) or total-body irradiation for haematological malignancies in childhood, remains difficult to disentangle as nearly always the cause of the growth disturbance is multifactorial: chemotherapy, graft-versus-host disease, hypothyroidism, and skeletal dysplasia may all impact on growth. There are few published data from which one can assess the efficacy of GH replacement on final height in those children who received cranial irradiation (18–24 Gy) and/or total-body irradiation; there is no evidence, however, of an increased risk of leukaemic relapse. Endocrine reassessment in the teenagers, who received cranial irradiation (18–24 Gy) for acute lymphoblastic leukaemia many years earlier, revealed a significant incidence of GH deficiency with the additional suggestion that many had been GH deficient for several years. This raises a number of important questions: What is the best way to organize long-term endocrine follow-up? How often should GH status be reassessed? What are the specific benefits of GH replacement in adult life for such individuals? These and other questions require further study.

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“…7,8,10 The prevalence of obesity at ®nal height in the survivors of ALL is approximately 4 ± 5 times that expected, 10 ± 12 and this may underestimate the magnitude of the problem since standard weight for height indices underestimate prevalence of excess adiposity. 4,13 Corticosteroids 9 and growth hormone insuf®-ciency following low-dose cranial irradiation (where it is still used 14 ) might contribute to excess weight gain in ALL, but the major cause of obesity on modern treatment protocols has recently been identi®ed as reduced habitual physical activity. 15,16 The appropriate clinical response to excess weight gain in ALL is unclear: while prevention of obesity is more effective than treatment, and is possible in childhood, 3 it is uncertain whether the focus of prevention should be on patients with ALL deemed to be at particularly`high risk' of developing obesity, or on all patients treated for ALL.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for excess weight gain in children treated for acute lymphoblastic leukaemia

Reilly

Ventham

Newell³

et al. 2000

Int J Obes

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OBJECTIVE: To test whether excess weight gain in patients treated for childhood acute lymphoblastic leukaemia (ALL) was predictable using patient characteristics at diagnosis. DESIGN AND SUBJECTS: Longitudinal study of changes in body mass index (BMI) in all 98 patients treated in Scotland on treatment protocol MRC UKALL-XI who had reached at least 3 y post-diagnosis in ®rst remission. MEASUREMENTS: The in¯uence of the following variables on changes in BMI, expressed as a standard deviation score (SDS), was tested using variable selection techniques and classi®cation and regression trees: BMI SDS at diagnosis; age at diagnosis; gender; socioeconomic status; treatment. RESULTS: Prevalence of obesity (BMI SDSb2.0) was`2% at diagnosis, but increased to 16% at 3 y. Gain in BMI SDS was signi®cantly inversely in¯uenced by BMI SDS at diagnosis (P`0.01) and age at diagnosis (P`0.01). CONCLUSION: Obesity is common in ALL by the end of therapy, and is more likely in children who are younger and thinner at diagnosis. Excess weight gain was not readily predictable from routinely collected information available at diagnosis and so all children treated for ALL should be considered`at risk' of excess weight gain and the target of obesity prevention.

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A novel variant of growth hormone (GH) insufficiencyfollowing low dose cranial irradiation

Abstract: A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.

Cited by 72 publications

References 23 publications

Energy Expenditure, Energy Intake and Prevalence of Obesity after Therapy for Acute Lymphoblastic Leukemia during Childhood

Energy Expenditure, Energy Intake and Prevalence of Obesity after Therapy for Acute Lymphoblastic Leukemia during Childhood

Growth and Growth Hormone Status following Treatment for Childhood Leukaemia

Risk factors for excess weight gain in children treated for acute lymphoblastic leukaemia

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