Irradiation-Induced Growth Hormone Neurosecretory Disfunction In ALL Patients

Abstract 4329

With the recent developments in the treatment of ALL life expectancy is prolonged and complications due to therapy are increased. Combined chemotherapy may be applied in combination with distinct doses and schema of cranial radiotherapy according to the risk groups of patients. CRT damages the hypothalamus-hypophysis axis and affects the secretion of growth hormone (GH) at first and the other anterior hypophysis hormones also. At high doses of CRT, GH deficiency might occur in the long term follow-up, at lower doses the secretion pattern of GH may change. In this study, GH axis of the ALL patients treated with prophylactic CRT were evaluated.

Thirty-two children (14 girls and 18 boys), diagnosed as ALL and applied prophylactic cranial therapy were enrolled to the study. Physical findings, weight and height measurements, Tanner stagings and bone age evaluations were performed to all patients. In order to interpret the functions of anterior and posterior hypophysis morning basal IGF-1, IGFBP-3, thyroid hormones, cortisol, prolactin and dansity of urine were measured. Gonodotrophins were not tested because none of our patients had the signs of early or late puberty. In order to evaluate the growth rate, weights and heights of the patients were measured after the first year. Even though the growth rate of some patients were normal, GH stimulation tests with clonidine were done to all cases, due to the fact that GH deficiency and neurosecretory dysfunction might be present pharmacologically. Second GH stimulation test with L-dopa were applied to patients with peak GH levels of <10 ng/ml. If the level was low in the second test, patients were accepted as GH deficient. For patients with low growth rate, low IGF-1/IGFBP-3 according to age and sex, but normal GH levels, night GH secretion pattern were tested. Patients with inadequate response to night secretion test were accepted as neurosecretory dysfunction.

In our study, 25% of the patients were found to have complete and 21,7% incomplete GH deficiency. In 9.3% of cases there was GH-neurosecretory dysfunction (GH_NSD). There was no statistically significant relationship between the time passed after radiotherapy and GH axis dysfunction degree. IGF-BP3 was found to be more reliable than IGF-1 in estimating GH deficiency/GH-NSD.

As a result, it is clear that prophylactic CRT affects the GH axis negatively in ALL patients, so their close follow-up is precious and mandatory.