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Cited by 619Pituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth FactorsEffects of Radiation Exposure

Hypothalamic-pituitary dysfunction after radiation for brain tumors

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Constine, Louis S., Woolf, Paul D., Cann, Donald, Mick, Gail, McCormick, Kenneth, Raubertas, Richard F., Rubin, Philip·1993·New England Journal of Medicine
DOI 10.1056/nejm199301143280203
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Abstract

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.

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  1. [1]1. Duffner PK, Cohen ME, Voorhess ML, et al. Long-term effects of cranial irradiation on endocrine function in children with brain tumors: a prospective study. Cancer 1985;56:2189-93.
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  4. [15]15. Kelly KH, Feldsted ET, Brown RF, et al. Irradiation of the normal human h y0 s s : s s s0 tissue dose to the pituitary gland. J Natl Cancer Inst 1951;11:967-83.
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Authors
Constine, L. S., Woolf, P. D., Cann, D., Mick, G., McCormick, K., Raubertas, R. F., & Rubin, P.
Affiliations
  • University of Rochester Medicine (US)
  • State University of New York (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1993-01-14
Volume
328
Issue
2
Pages
87-94
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199301143280203
OpenAlex
W2329522359
Cited by
619
References
38
Citations by year
2026: 6 · 2025: 2 · 2024: 9 · 2023: 12 · 2022: 22 · 2021: 15 · 2020: 16 · 2019: 32 · 2018: 28 · 2017: 17 · 2016: 21 · 2015: 21 · 2014: 23 · 2013: 16 · 2012: 24
FWCI
11.13
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (RR-00044, M01RR000044)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
hypothalamic-pituitary dysfunction, cranial irradiation, brain tumors, hypothyroidism, hypogonadism, hyperprolactinemia, adrenal insufficiency, growth hormone deficiency, metyrapone test, pituitary stimulation test, long-term radiation effects, children and adolescents
MeSH terms
Adolescent, Adrenal Glands, Adult, Aged, Brain Neoplasms, Child, Female, Gonads, Humans, Hyperprolactinemia, Hypogonadism, Hypothalamus, Hypothyroidism, Male, Middle Aged, Pituitary Gland, Radiation Dosage, Radiotherapy, Thyroid Gland, Thyroid Hormones

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