Growth Hormone Secretion and Response to Growth Hormone Therapy after Treatment for Brain Tumour

Abstract

Lannering, B., Marky, I., Mellander, L. and Albertsson-Wikland, K. (Departments of Paediatrics I, I1 and Physiology, Gothenburg University, Gothenburg, Sweden). Growth hormone secretion and response to growth hormone after treatment for brain tumour. Acta Paediatr Scand [Suppl] 343:146, 1988. Children irradiated for brain tumours constitute an increasing group of patients who will require GH therapy. High-dose cranial irradiation is necessary for cure, but inevitably causes GH deficiency within a few years. In 19 patients investigated between 2 and 9 years after irradiation, the spontaneous 24-hour GH secretion was markedly reduced. The secretory pattern indicated loss of regulating hypothalamic hormones. After exogenous GHRH was administered, the pituitary was able to respond with a prompt GH release, showing that pituitary function was unaffected. Ten prepubertal children growing at 3.8 1 0.3 cm/year were treated with GH, 0.1 IU/kg/day S.C. Their growth rate increased to 8.2 f 0.4 cm in the first year. An increased growth rate was also maintained in the second year. Key words: Cranial irradiation, brain tumour, GH therapy, 24-hour GH profiles.Brain tumours are the most common solid tumours in childhood with an incidence of 3/100,000 children. About 70% of the tumours require irradiation for cure.Postoperative radiotherapy has so far been the single major advance in the treatment of malignant brain tumours (1). It has enabled a 50% 5-year disease-free survival for medulloblastomas ( 2 ) . Radiotherapy is given with a high irradiation dose (55 Gy) to the . t m o u r site and also to the whole brain (3&35 Gy) to prevent meningeal spread -the hypothilamic-pituitary axis thus inevitably receives irradiation. It is hoped that there will be more children surviving malignant brain turnours without severe sequelae in the future (3). Improved imaging methods, better operative techniques and new treatment protocols will contribute to this (4, 5). GH dysfunction, however, will continye to be a problem that has to be dealt with in an optimal way. In this study, data are presented to illustrate what the authors find to be the optimal way to diagnose and treat radiation-induced G H deficiency. PATIENTSThe study included 19 children who were between 1 and 16.9 years old at the time of radiotherapy for a brain tumour (n=16) or a cranial turnour (n=3). High-dose radiotherapy (>40 Gy) was given between 1970 and 1982 to the hypothalamic-pituitary region. The clinical data of the patients are listed in Table 1. The time from radiotherapy to G H investigation was at least 2 years, with a mean of 4 years. By then the patients were between 5 and 23 years old. About half of the patients had received chemotherapy for 1 year postoperatively.Control group A consisted of 20 children with constitutional short stature, growing below -2 SD, aged 6-14 years. Control group B comprised 24 healthy children growing between -2 SD and + 2 SD, aged 8-15 years. METHODS AND RESULTSGrowth deviation. Those children who were prepubertal at diagnosis an...

Pathophysiology of radiation-induced growth hormone deficiency: Efficacy and safety of GH replacement

“…For example, Brauner et al [68] showed that after 2 years of followup, children treated with cranial and spinal irradiation had a mean height SDS of 1.46 ± 0.40 below the normal mean, while children given only cranial irradiation (with a similar dose) had a mean height SDS that was À0.15 ± 0.18 (P < 0.02). Thus, spinal irradiation seems to be the major contributing factor to impaired growth in the first few years after irradiation, while GHD becomes increasingly more important in later years, with height loss that can exceed 2 SDS [70][71][72][73][74][75].…”

Intratumor microbiome derived glycolysis-lactate signatures depicts immune heterogeneity in lung adenocarcinoma by integration of microbiomic, transcriptomic, proteomic and single-cell data

“…Glycolysis is one of the most common metabolic pathways of reprogramming, that converts glucose into pyruvate and lactate, generating ATP and NADH as energy sources under aerobic or anaerobic conditions ( Ganapathy-Kanniappan and Geschwind, 2013 ). Many cancer cells enhance glycolysis, allowing them to adapt to hypoxic and nutrient-poor conditions and evade immune surveillance ( Lannering et al, 1988 ). This aberrant glycolysis in tumors can increase lactate production that alters the pH of the tumor microenvironment, affecting both cancer cells and immune cells ( Vaupel and Multhoff, 2021 ).…”