title: Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.
abstract: The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures.
  
  
  
  We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings.
  
  
  
  The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m(2) or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all).
  
  
  
  Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA. moab@e-mail.chop.edu.
authors.forename: Sogol
authors.initials: S
authors.lastname: Mostoufi-Moab
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Oeffinger
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Lillian R
authors.initials: LR
authors.lastname: Meacham
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Rita
authors.initials: R
authors.lastname: Weathers
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Ginsberg
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Sogol Mostoufi-Moab and Jill P. Ginsberg, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kristy Seidel and Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Gregory T. Armstrong, Daniel M. Green, and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan Kettering Cancer Center, New York, NY; Marilyn Stovall and Rita Weathers, University of Texas MD Anderson Cancer Center, Houston, TX; and Lillian R. Meacham, Emory University, Atlanta, GA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004700:Endocrine System Diseases / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D012189:Retrospective Studies; D017741:Survivors / Q000706:statistics & numerical data*; D014481:United States / Q000453:epidemiology; D055815:Young Adult