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Anterior Hypopituitarism in Adult Survivors of Childhood Cancers Treated With Cranial Radiotherapy: A Report From the St Jude Lifetime Cohort Study
Open accessAbstract
Purpose: To estimate the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulatin hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after cranial radiotherapy (CRT) in childhood cancer survivors (CCS) and assess the impact of untreated deficiencies. Patients and Methods: Retrospective study in an established cohort of CCS with 748 participants treated with CRT (394 men; mean age, 34.2 years [range, 19.4 to 59.6 years] observed for a mean of 27.3 years [range, 10.8 to 47.7 years]). Multivariable logistic regression was used to study associations between demographic and treatment-related risk factors and pituitary deficiencies, as well as associations between untreated deficiencies and cardiovascular health, bone mineral density (BMD), and physical fitness. Results: The estimated point prevalence was 46.5% for GHD, 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD, and the cumulative incidence increased with follow-up. GHD and LH/FSHD were not treated in 99.7% and 78.5% of affected individuals, respectively. Male sex and obesity were significantly associated with LH/FSHD; white race was significant associated with LH/FSHD and TSHD. Compared with CRT doses less than 22 Gy, doses of 22 to 29.9 Gy were significantly associated with GHD; doses ≥ 22 Gy were associated with LH/FSHD; and doses ≥ 30 Gy were associated with TSHD and ACTHD. Untreated GHD was significantly associated with decreased muscle mass and exercise tolerance; untreated LH/FSHD was associated with hypertension, dyslipidemia, low BMD, and slow walking; and both deficits, independently, were associated with with abdominal obesity, low energy expenditure, and muscle weakness. Conclusion: Anterior pituitary deficits are common after CRT. Continued development over time is noted for GHD and LH/FSHD with possible associations between nontreatment of these conditions and poor health outcomes.
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“Additional risk factors include HP tumor involvement, young age at diagnosis, and use of tyrosine kinase inhibitors or anti-CTLA4 monoclonal antibodies (5,25).”
From Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers (2018) · cites this paper as [25]
In the citing paper
“GHD is also radiation dose-dependent, with the highest risk after HP radiation with $30 Gy; however, risks also occur after 18 to 30 Gy, after TBI with $10 Gy in one fraction, and after TBI with $12 Gy in multiple fractions.”
From Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers (2018) · cites this paper as [25]
In the citing paper
“The risk of GHD increases in a time-dependent fashion in relation to radiotherapy, and its prevalence thus increases with longer follow-up durations.”
From Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers (2018) · cites this paper as [25]
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Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis
Kazlauskaite, R., Evans, A. T., Villabona, C. V., Abdu, T. A. M., Ambrosi, B., Atkinson, A. B., Choi, C. H., Clayton, R. N., Courtney, C. H., Gonc, E. N., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0710 · Cited by 385 · cited 4×
“testing was not available and given the limitations in using baseline IGF-1 and 8:00 am cortisol levels to define GHD and ACTHD respectively, we have referred to our prevalence findings for these outcomes as estimates.(12,13) Previously unknown pituitary deficiencies diagnosed through participation in SJLIFE were desc…”
InfluentialCohen, A., Dempster, D. W., Recker, R. R., Lappe, J. M., Zhou, H., Zwahlen, A., Müller, R., Zhao, B., Guo, X., Lang, T., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1047 · Cited by 206
Cited by
Sklar, C. A., Antal, Z., Chemaitilly, W., Cohen, L. E., Follin, C., Meacham, L. R., & Murad, M. H. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01175 · Cited by 224
Self-citationBoguszewski, M. C. S., Boguszewski, C. L., Chemaitilly, W., Cohen, L. E., Gebauer, J., Higham, C., Hoffman, A. R., Polak, M., Yuen, K. C. J., Alos, N., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-21-1186 · Cited by 117
Self-citationReproductive Complications in Childhood Cancer Survivors
van Santen, H. M., van de Wetering, M. D., Bos, A. M. E., vd Heuvel-Eibrink, M. M., van der Pal, H. J., & Wallace, W. H. (2020) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2020.08.003 · Cited by 42
Diagnosis of GH Deficiency as a Late Effect of Radiotherapy in Survivors of Childhood Cancers
Sfeir, J. G., Kittah, N. E. N., Tamhane, S. U., Jasim, S., Chemaitilly, W., Cohen, L. E., & Murad, M. H. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01204 · Cited by 35
Self-citationPartin, R. E., Wogksch, M. D., Dhaduk, R., Ashford, J. M., Indelicato, D. J., Conklin, H. M., Merchant, T. E., & Ness, K. K. (2022) · Journal of Neuro-Oncology · doi:10.1007/s11060-022-04116-2 · Cited by 8
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Metadata
- Authors
- Chemaitilly, W., Li, Z., Huang, S., Ness, K. K., Clark, K. L., Green, D. M., Barnes, N., Armstrong, G. T., Krasin, M. J., Srivastava, D. K., Pui, C.-H., Merchant, T. E., Kun, L. E., Gajjar, A., Hudson, M. M., Robison, L. L., & Sklar, C. A.
- Venue
- Journal of Clinical Oncology
- Published
- 2015-02-10
- Volume
- 33
- Issue
- 5
- Pages
- 492-500
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2048576559
- Cited by
- 281
- References
- 10
- FWCI
- 19.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Chemaitilly, W., Li, Z., Huang, S., Ness, K. K., Clark, K. L., Green, D. M., Barnes, N., Armstrong, G. T., Krasin, M. J., Srivastava, D. K., Pui, C.-H., Merchant, T. E., Kun, L. E., Gajjar, A., Hudson, M. M., Robison, L. L., & Sklar, C. A. (2015). Anterior Hypopituitarism in Adult Survivors of Childhood Cancers Treated With Cranial Radiotherapy: A Report From the St Jude Lifetime Cohort Study. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2014.56.7933
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