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Hypothalamic-Pituitary Dysfunction after Radiation for Brain Tumors
Open accessAbstract
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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“Hypothyroidism has been described in up to 65% of cases many years after conventional radiotherapy (Constine et al., 1993;Kyriakakis et al., 2015;Snyder et al., 1986).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Constine et al., 1993
In the citing paper
“oral oestrogen replacement increases all binding proteins by stimulating their hepatic synthesis.”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Constine et al., 1993
In the citing paper
“but also putting a further strain on the production of thyroid hormones in cases of mild or latent hypothyroidism on the other (Constine et al., 1993;Feldt-Rasmussen, 2018;Filipsson and Johannsson, 2009).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Constine et al., 1993
In the citing paper
“The subsequent increased thyroxine binding globulin therefore challenges the interpretation of thyroid hormone measurements on the one hand”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Constine et al., 1993
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Metadata
- 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)
- 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
- 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
- bronze
- doi.org
- 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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