title: Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY. wassim.chemaitilly@stjude.org.
authors.forename: Wassim
authors.initials: W
authors.lastname: Chemaitilly
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Clark
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Nicole
authors.initials: N
authors.lastname: Barnes
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Krasin
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Wassim Chemaitilly, Zhenghong Li, Sujuan Huang, Kirsten K. Ness, Karen L. Clark, Daniel M. Green, Nicole Barnes, Gregory T. Armstrong, Matthew J. Krasin, Deo Kumar Srivastava, Ching-Hon Pui, Thomas E. Merchant, Larry E. Kun, Amar Gajjar, Melissa M. Hudson, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000328:Adult; D015519:Bone Density; D002648:Child; D016371:Cranial Irradiation / Q000009:adverse effects*; D004734:Energy Metabolism; D017079:Exercise Tolerance; D005260:Female; D005640:Follicle Stimulating Hormone / Q000172:deficiency; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D015994:Incidence; D007986:Luteinizing Hormone / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness; D009369:Neoplasms / Q000532:radiotherapy*; D010809:Physical Fitness; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000528:radiation effects*; D015995:Prevalence; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017741:Survivors; D013714:Tennessee / Q000453:epidemiology; D013972:Thyrotropin / Q000172:deficiency; D013997:Time Factors; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin