Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-hodgkins lymphoma: A study of pulsatile growth hormone and gonadotropin secretions

To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 ± 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2,400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 µg/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data. We conclude (a) that GH deficiency is a common finding among children who receive 2,400 rads of cranial irradiation, and that 24-h GH secretory profiles and standard pharmacologic GH stimulation tests are sensitive indicators of the dysfunction; (b) that treatment with GH should be reserved for children with GH deficiency, documented either by pharmacologic stimuli or by 24-h studies, and should not be used in every short child that received relatively modest doses of cranial irradiation; (c) that in our two GH-deficient patients, the dysfunction may not be hypothalamic, and (d) that the prepubertal gonadotrophs are relatively resistant to the biologic effects of modest doses (2,400 rads) of ionizing radiation.