{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:11:50Z","timestamp":1791893510010,"version":"4.3.4"},"reference-count":41,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:p>Context: Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors.<\/jats:p>\n               <jats:p>Objective: The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors.<\/jats:p>\n               <jats:p>Method: We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12\u2013150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients.<\/jats:p>\n               <jats:p>Results: Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient.<\/jats:p>\n               <jats:p>Conclusion: Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.<\/jats:p>","DOI":"10.1210\/jc.2005-1525","type":"journal-article","created":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T23:38:01Z","timestamp":1133825881000},"page":"6355-6360","source":"Crossref","is-referenced-by-count":163,"title":["Hypothalamic-Pituitary Dysfunction after Irradiation of Nonpituitary Brain Tumors in Adults"],"prefix":"10.1210","volume":"90","author":[{"given":"Amar","family":"Agha","sequence":"first","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sherlock","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead","family":"Brennan","sequence":"additional","affiliation":[{"name":"Beaumont Hospital and Division of Radiation Oncology (S.B., C.F.), St. Luke\u2019s Hospital, Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eoin","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bairbre","family":"Rogers","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Faul","sequence":"additional","affiliation":[{"name":"Beaumont Hospital and Division of Radiation Oncology (S.B., C.F.), St. Luke\u2019s Hospital, Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rawluk","sequence":"additional","affiliation":[{"name":"Neurosurgery (D.R.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tormey","sequence":"additional","affiliation":[{"name":"Clinical Chemistry (W.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Divisions of Endocrinology (A.A., M.S., S.A.O., E.O., B.R., C.J.T.), Dublin 9, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071615594768700_R1","first-page":"145","article-title":"Hypopituitarism following external radiotherapy for pituitary tumours in adults.","volume":"70","author":"Littley","year":"1989","journal-title":"Q J Med"},{"key":"2020071615594768700_R2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0140-6736(75)90006-9","article-title":"Pituitary function after treatment of intracranial tumours in children.","volume":"2","author":"Shalet","year":"1975","journal-title":"Lancet"},{"key":"2020071615594768700_R3","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/0360-3016(77)90166-3","article-title":"Hypopituitarism after irradiation in children.","volume":"2","author":"Wara","year":"1977","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2020071615594768700_R4","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1002\/1097-0142(19820415)49:8<1580::AID-CNCR2820490810>3.0.CO;2-7","article-title":"Assessment of the long-term effects of primary radiation therapy for brain tumors in children.","volume":"49","author":"Danoff","year":"1982","journal-title":"Cancer"},{"key":"2020071615594768700_R5","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1210\/jcem-68-2-346","article-title":"A prospective study of the development of growth hormone deficiency in children given cranial irradiation, and its relation to statural growth.","volume":"68","author":"Brauner","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R6","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S0022-3476(05)80487-1","article-title":"Dose dependency of time of onset of radiation-induced growth hormone deficiency.","volume":"118","author":"Clayton","year":"1991","journal-title":"J Pediatr"},{"issue":"Suppl A","key":"2020071615594768700_R7","doi-asserted-by":"crossref","first-page":"S118","DOI":"10.1016\/j.ghir.2004.03.038","article-title":"Endocrine consequences of brain irradiation","volume":"14","author":"Toogood","year":"2004","journal-title":"Growth Horm IGF Res"},{"key":"2020071615594768700_R8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/mpo.10267","article-title":"Hypothalamo-pituitary-adrenal axis integrity after cranial irradiation for childhood posterior fossa tumours.","volume":"40","author":"Spoudeas","year":"2003","journal-title":"Med Pediatr Oncol"},{"key":"2020071615594768700_R9","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/0360-3016(82)90442-4","article-title":"Hypothalamic pituitary dysfunction after radiotherapy to the head and neck.","volume":"8","author":"Samaan","year":"1982","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2020071615594768700_R10","first-page":"165","article-title":"Effects of cranial irradiation on hypothalamic\u2013pituitary function\u2014a 5-year longitudinal study in patients with nasopharyngeal carcinoma.","volume":"78","author":"Lam","year":"1991","journal-title":"Q J Med"},{"key":"2020071615594768700_R11","first-page":"265","article-title":"Endocrine and reproductive dysfunction following fractionated total body irradiation in adults.","volume":"78","author":"Littley","year":"1991","journal-title":"Q J Med"},{"key":"2020071615594768700_R12","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1136\/adc.67.9.1107","article-title":"Endocrine deficit after fractionated total body irradiation.","volume":"67","author":"Ogilvy-Stuart","year":"1992","journal-title":"Arch Dis Child"},{"key":"2020071615594768700_R13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1046\/j.1365-2265.2000.01079.x","article-title":"Cranial radiotherapy of childhood brain tumours: growth hormone deficiency and its relation to the biological effective dose of irradiation in a large population based study.","volume":"53","author":"Schmiegelow","year":"2000","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/bjs.1800560315","article-title":"The adrenocortical response to surgery and insulin-induced hypoglycaemia in corticosteroid-treated and normal subjects.","volume":"56","author":"Plumpton","year":"1969","journal-title":"Br J Surg"},{"key":"2020071615594768700_R15","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0026-0495(86)90245-3","article-title":"Endocrine and neurophysiological responses of the pituitary to insulin-induced hypoglycemia: a review.","volume":"35","author":"Fish","year":"1986","journal-title":"Metabolism"},{"key":"2020071615594768700_R16","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0140-6736(94)90181-3","article-title":"Diagnosis of growth hormone deficiency in adults.","volume":"343","author":"Hoffman","year":"1994","journal-title":"Lancet"},{"key":"2020071615594768700_R17","first-page":"379","article-title":"Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency.","volume":"83","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R18","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/0026-0495(87)90150-8","article-title":"Intramuscular glucagon as a provocative stimulus for the assessment of pituitary function: growth hormone and cortisol responses.","volume":"36","author":"Rao","year":"1987","journal-title":"Metabolism"},{"key":"2020071615594768700_R19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1046\/j.1365-2265.1996.d01-1562.x","article-title":"Comparison of tests of stress-released cortisol secretion in pituitary disease.","volume":"45","author":"Orme","year":"1996","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R20","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1046\/j.1365-2265.2001.01169.x","article-title":"An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease.","volume":"54","author":"Leong","year":"2001","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1046\/j.1365-2265.2002.01472.x","article-title":"Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults.","volume":"56","author":"Gomez","year":"2002","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R22","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/j.1365-2265.2004.02023.x","article-title":"Neuroendocrine dysfunction in the acute phase of traumatic brain injury.","volume":"60","author":"Agha","year":"2004","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1210\/edrv.19.2.0329","article-title":"The diagnosis of growth hormone deficiency in children and adults.","volume":"19","author":"Shalet","year":"1998","journal-title":"Endocr Rev"},{"key":"2020071615594768700_R24","first-page":"663","article-title":"The impact of irradiation on growth hormone responsiveness to provocative agents is stimulus dependent: results in 161 individuals with radiation damage to the somatotropic axis.","volume":"86","author":"Lissett","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R25","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/S0140-6736(88)92020-X","article-title":"A rational approach for assessing the hypothalamo-pituitary-adrenal axis.","volume":"1","author":"Stewart","year":"1988","journal-title":"Lancet"},{"key":"2020071615594768700_R26","first-page":"263","article-title":"Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: the short synacthen versus the insulin tolerance test.","volume":"88","author":"Kane","year":"1995","journal-title":"Q J Med"},{"key":"2020071615594768700_R27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1365-2265.1996.666478.x","article-title":"Short synacthen test versus insulin stress test for assessment of the hypothalamo pituitary\u2013adrenal axis: controversy revisited.","volume":"44","author":"Clayton","year":"1996","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1365-2265.1992.tb00947.x","article-title":"A retrospective audit of the combined pituitary function test, using the insulin stress test, TRH and GnRH in a district laboratory.","volume":"36","author":"Pavord","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1365-2265.1992.tb00946.x","article-title":"The pituitary megatest: outdated?","volume":"36","author":"Burke","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R30","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1210\/jc.2004-0511","article-title":"Anterior pituitary dysfunction in survivors of traumatic brain injury.","volume":"89","author":"Agha","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R31","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/bjc.1990.138","article-title":"Endocrine disorders following treatment of childhood brain tumours.","volume":"61","author":"Livesey","year":"1990","journal-title":"Br J Cancer"},{"key":"2020071615594768700_R32","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1210\/jc.2002-021994","article-title":"Assessment of the hypothalamo-pituitary-adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumor.","volume":"88","author":"Schmiegelow","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1056\/NEJM199301143280211","article-title":"Radiation and pituitary dysfunction.","volume":"328","author":"Shalet","year":"1993","journal-title":"N Engl J Med"},{"key":"2020071615594768700_R34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1365-2265.1976.tb01960.x","article-title":"Hypothalamic-pituitary function following successful treatment of intracranial tumours.","volume":"5","author":"Harrop","year":"1976","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1365-2265.1989.tb01260.x","article-title":"Radiation induced hypopituitarism is dose dependent.","volume":"31","author":"Littley","year":"1989","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071615594768700_R36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1056\/NEJM199301143280203","article-title":"Hypothalamic-pituitary dysfunction after radiation for brain tumors.","volume":"328","author":"Constine","year":"1993","journal-title":"N Engl J Med"},{"issue":"Suppl 1","key":"2020071615594768700_R37","first-page":"1","article-title":"Radiation-induced growth hormone deficiency","volume":"59","author":"Darzy","year":"2003","journal-title":"Horm Res"},{"key":"2020071615594768700_R38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0950-351X(05)80321-0","article-title":"Radiation and hypothalamic-pituitary function.","volume":"4","author":"Littley","year":"1990","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"2020071615594768700_R39","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1210\/jcem.87.1.8146","article-title":"GH-deficient survivors of childhood cancer: GH replacement during adult life.","volume":"87","author":"Murray","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R40","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1210\/jcem.87.7.8606","article-title":"Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study.","volume":"87","author":"Sklar","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071615594768700_R41","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1470-2045(05)70095-4","article-title":"Lessons learned from randomised clinical trials in adult low grade glioma.","volume":"6","author":"Papagikos","year":"2005","journal-title":"Lancet Oncol"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/12\/6355\/10777400\/jcem6355.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/12\/6355\/10777400\/jcem6355.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T03:04:31Z","timestamp":1594955071000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/90\/12\/6355\/2837141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,1]]},"references-count":41,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2005,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2005-1525","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,12,1]]}}}