Pituitary dysfunction following cranial radiotherapy for adult-onset nonpituitary brain tumours
Abstract
OBJECTIVE: There are limited data concerning the evolution of radiation-induced hypopituitarism in adult-onset brain tumour (AO-BT) survivors, in part the consequence of the limited survival of many of these individuals. We aim to characterize the pituitary-related outcomes following cranial radiotherapy (cXRT) for adult-onset primary nonpituitary brain tumours. DESIGN: We retrospectively analysed longitudinal data of patients with AO-BT who received cXRT within a tertiary cancer referral centre. PATIENTS: A total of 107 adults (age 40·0 ± 13·1 years) followed for a median duration of 8 years following cXRT. MEASUREMENTS: Prevalence of radiotherapy-induced hypopituitarism. RESULTS: 94·4% received fractionated photon radiotherapy (median dose 54 Gy), while the remaining patients received proton beam or stereotactic radiotherapy. 88·8% of patients developed hypopituitarism during follow-up. The frequency of GH, gonadotrophin, ACTH and TSH deficiencies was 86·9% (severe GHD 64·5%, partial GHD 22·4%), 34·6%, 23·4% and 11·2%, respectively. ACTH deficiency was clinically significant, necessitating glucocorticoid replacement, in only 10·3% of cases. Hyperprolactinaemia developed in 15% of patients, which was persistent in only 50% of cases. Multiple pituitary hormone deficiencies were present in 47·7% of patients, encountered more frequently in patients with tumours in proximity to the sella. Longitudinal data analysis revealed accumulation of hormone deficits throughout the follow-up period, with incidence of all pituitary hormone deficiencies almost doubling between years 2 and 7 of follow-up. CONCLUSIONS: Pituitary dysfunction in AO-BT survivors following cXRT is a common, evolving, time-dependent phenomenon. It is important that deficits are identified early and replacement therapies introduced to optimize quality of life in these individuals, where prognosis is often guarded.
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Hypothyroidism has been described in up to 65% of cases many years after conventional radiotherapy.
“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 Kyriakakis et al., 2015
Cites
Hypopituitarism Following External Radiotherapy for Pituitary Tumours in Adults
LITTLEY, M. D., SHALET, S. M., BEARDWELL, C. G., AHMED, S. R., APPLEGATE, G., & SUTTON, M. L. (1989) · QJM: An International Journal of Medicine · doi:10.1093/oxfordjournals.qjmed.a068308 · Cited by 444 · see citing works
Markoe, A. M. (1988) · American Journal of Clinical Oncology · doi:10.1097/00000421-198804000-00021 · Cited by 335 · see citing works
RADIATION‐INDUCED HYPOPITUITARISM IS DOSE‐DEPENDENT
Littley, M. D., Shalet, S. M., Beardwell, C. G., ROBINSON, E. L., & Sutton, M. (1989) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1989.tb01260.x · Cited by 271 · see citing works
Endocrine deficit after fractionated total body irradiation.
Ogilvy‐Stuart, A., Clark, D., Wallace, W. H., Gibson, B. E. S., Stevens, R., Shalet, S. M., & Donaldson, M. (1992) · Archives of Disease in Childhood · doi:10.1136/adc.67.9.1107 · Cited by 198 · see citing works
Pai, H. H., Thornton, A. F., Katznelson, L. J., Finkelstein, D. M., Adams, J., Fullerton, B. C., Loeffler, J. S., Leibsch, N. J., Klibanski, A., & Munzenrider, J. E. (2001) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(00)01387-0 · Cited by 195 · see citing works
Dose dependency of time of onset of radiation-induced growth hormone deficiency
Clayton, P., & Shalet, S. M. (1991) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80487-1 · Cited by 192 · see citing works
Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults.
Agha, A., Sherlock, M., Brennan, S., O'Connor, S., O'Sullivan, E. P., Rogers, B., Faul, C., Rawluk, D., Tormey, W., & Thompson, C. (2005) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2005-1525 · Cited by 182 · see citing works
LAM, K., TSE, V., Wang, C., Yeung, R. T., & Ho, J. (1991) · QJM · doi:10.1093/oxfordjournals.qjmed.a068535 · Cited by 180 · see citing works
Rahim, A., Toogood, A. A., & Shalet, S. M. (1996) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1996.00855.x · Cited by 159 · see citing works
Radiation-induced hypopituitarism after cancer therapy: who, how and when to test
Darzy, K. H. (2009) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet1051 · Cited by 150 · see citing works
Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck
Samaan, N. A., Vieto, R., Schultz, P. N., Maor, M. H., Meoz, R. T., Sampiere, V. A., Cangır, A., Ried, H. L., & Jesse, R. H. (1982) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(82)90442-4 · Cited by 147 · see citing works
Radiological and clinical assessment of long-term brain tumour survivors after radiotherapy
Johannesen, T. B., Lien, H. H., Hole, K. H., & Lote, K. (2003) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(03)00192-0 · Cited by 141 · see citing works
Hypopituitarism following Radiotherapy Revisited
Darzy, K. H., & Shalet, S. M. (2009) · Endocrine development · doi:10.1159/000207607 · Cited by 138 · see citing works
Endocrine and Reproductive Dysfunction Following Fractionated Total Body Irradiation in Adults
Littley, M. D., Shalet, S. M., Morgenstern, G. R., & Deakin, D. P. (1991) · QJM · doi:10.1093/oxfordjournals.qjmed.a068546 · Cited by 125 · see citing works
Schmiegelow, Lassen, Poulsen, Feldt‐Rasmussen, Schmiegelow, Hertz, & Müller (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01079.x · Cited by 115 · see citing works
Brauner, R., Rappaport, R., Prévôt, C., Czernichow, P., Zucker, J., Bataïni, P., Lemerle, J., Sarrazin, D., & Guyda, H. J. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-2-346 · Cited by 95 · see citing works
Radiation and Pituitary Dysfunction
Shalet, S. M. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301143280211 · Cited by 94 · see citing works
9 Radiation and hypothalamic—pituitary function
Littley, M. D., Shalet, S. M., & Beardwell, C. G. (1990) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80321-0 · Cited by 59 · see citing works
Endocrine dysfunction in patients operated on for non-pituitary intracranial tumors
Schneider, H., Rovere, S., Corneli, G., Croce, C. G., Gasco, V., Rudà, R., Grottoli, S., Stalla, G. K., Soffietti, R., Ghigo, E., et al. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02272 · Cited by 51 · see citing works
Madaschi, S., Fiorino, C., Losa, M., Lanzi, R., Elena, M., Motta, M., Lucia, P. A. D., Brioschi, E., Scavini, M., & Reni, M. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.02.015 · Cited by 44 · see citing works
Chen, M.-S., Lin, F., Mj, H., Wang, P.-W., Tang, S. F. T., Leung, W.-M., & Leung, W. (1989) · Japanese Journal of Clinical Oncology · doi:10.1093/oxfordjournals.jjco.a039312 · Cited by 35 · see citing works
Lessons learned from randomised clinical trials in adult low grade glioma
Papagikos, M. A., Shaw, E. G., & Stieber, V. W. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70095-4 · Cited by 29 · see citing works
Murray, R. D., Bidlingmaier, M., Strasburger, C. J., & Shalet, S. M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2055 · Cited by 27 · see citing works
Self-citationHypopituitarism after radiotherapy for extracranial head and neck cancers
Bhandare, N., Kennedy, L., Malyapa, R. S., Morris, C. G., & Mendenhall, W. M. (2008) · Head & Neck · doi:10.1002/hed.20847 · Cited by 27 · see citing works
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Feldt-Rasmussen, U., Effraimidis, G., & Klose, M. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111173 · Cited by 170 · see citing works
Central hypothyroidism — a neglected thyroid disorder
Beck-Peccoz, P., Rodari, G., Giavoli, C., & Lania, A. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.47 · Cited by 140 · see citing works
Garrahy, A., Sherlock, M., & Thompson, C. J. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0962 · Cited by 53 · see citing works
- Authors
- Kyriakakis, N., Lynch, J., Orme, S. M., Gerrard, G., Hatfield, P., Loughrey, C., Short, S. C., & Murray, R. D.
- Affiliations
- Leeds Teaching Hospitals NHS Trust (GB)
- Corresponding author
- Murray, Robert D.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2015-11-24
- Volume
- 84
- Issue
- 3
- Pages
- 372-379
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1848109215
- Cited by
- 77
- References
- 24
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 11 · 2018: 8 · 2017: 10 · 2016: 3
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (ACF-2016-02-005)
- 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 › Genetics › Glioma Diagnosis and Treatment
- Keywords
- radiation-induced hypopituitarism, cranial irradiation, growth hormone deficiency, ACTH deficiency, gonadotropin deficiency, TSH deficiency, hyperprolactinemia, multiple pituitary hormone deficiency, hormone replacement therapy, proton beam radiotherapy, stereotactic radiotherapy
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Brain Neoplasms, Dwarfism, Pituitary, Female, Follow-Up Studies, Humans, Hypopituitarism, Longitudinal Studies, Male, Middle Aged, Pituitary Gland, Retrospective Studies, Cranial Irradiation, Outcome Assessment, Health Care, Tertiary Care Centers
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