Hypothalamic-Pituitary Dysfunction after Radiation for Brain Tumors

Academic Article


  • Background: Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. Methods: We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. Results: Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. Conclusions: Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present., Children and adults with brain tumors who are treated with cranial radiation may subsequently have deficits in neuroendocrine function1–13. Although deficiency of growth hormone is common, hypothyroidism and gonadal disturbances are seldom reported and are presumed to occur only after particularly high doses of radiation14–18. This underestimation of the threshold doses of radiation capable of damaging the hypothalamic-pituitary axis results from the lack of dose-related studies of patients evaluated at intervals sufficiently long for the sequelae of radiation to become evident. With respect to the secretion of growth hormone, 65 percent of children with acute lymphoblastic… © 1993, Massachusetts Medical Society. All rights reserved.
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    Author List

  • Constine LS; Woolf PD; Cann D; Mick G; McCormick K; Raubertas RF; Rubin P
  • Start Page

  • 87
  • End Page

  • 94
  • Volume

  • 328
  • Issue

  • 2