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      Hypothalamic-Pituitary Disorders in Childhood Cancer Survivors: Prevalence, Risk Factors and Long-Term Health Outcomes

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          Abstract

          Context

          Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited.

          Objective

          To describe prevalence, risk factors, and associated adverse health outcomes of deficiencies in GH deficiency (GHD), TSH deficiency (TSHD), LH/FSH deficiency (LH/FSHD), and ACTH deficiency (ACTHD), and central precocious puberty (CPP).

          Design

          Retrospective with cross-sectional health outcomes analysis.

          Setting

          Established cohort; tertiary care center.

          Patients

          Participants (N = 3141; median age, 31.7 years) were followed for a median 24.1 years.

          Main Outcome Measure

          Multivariable logistic regression was used to calculate ORs and 95% CIs for associations among HP disorders, tumor- and treatment-related risk factors, and health outcomes.

          Results

          The estimated prevalence was 40.2% for GHD, 11.1% for TSHD, 10.6% for LH/FSHD, 3.2% for ACTHD, and 0.9% for CPP among participants treated with HP radiotherapy (n = 1089), and 6.2% for GHD, and <1% for other HP disorders without HP radiotherapy. Clinical factors independently associated with HP disorders included HP radiotherapy (at any dose for GHD, TSHD, LH/FSHD, >30 Gy for ACTHD), alkylating agents (GHD, LH/FSHD), intrathecal chemotherapy (GHD), hydrocephalus with shunt placement (GHD, LH/FSHD), seizures (TSHD, ACTHD), and stroke (GHD, TSHD, LH/FSHD, ACTHD). Adverse health outcomes independently associated with HP disorders included short stature (GHD, TSHD), severe bone mineral density deficit (GHD, LH/FSHD), obesity (LH/FSHD), frailty (GHD), impaired physical health-related quality of life (TSHD), sexual dysfunction (LH/FSHD), impaired memory, and processing speed (GHD, TSHD).

          Conclusion

          HP radiotherapy, central nervous system injury, and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes.

          Abstract

          In a large cohort of systematically assessed childhood cancer survivors, associations between HP disorders, tumor and treatment variables, and adverse health outcomes were elicited.

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          Author and article information

          Journal
          J Clin Endocrinol Metab
          J. Clin. Endocrinol. Metab
          jcem
          The Journal of Clinical Endocrinology and Metabolism
          Endocrine Society (Washington, DC )
          0021-972X
          1945-7197
          December 2019
          02 August 2019
          02 August 2020
          : 104
          : 12
          : 6101-6115
          Affiliations
          [1 ] Division of Endocrinology, St. Jude Children’s Research Hospital , Memphis, Tennessee
          [2 ] Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital , Utrecht, Netherlands
          [3 ] Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital , Memphis, Tennessee
          [4 ] Department of Biostatistics, St. Jude Children's Research Hospital , Memphis, Tennessee
          [5 ] Department of Psychology, St. Jude Children’s Research Hospital , Memphis, Tennessee
          [6 ] Department of Oncology, St. Jude Children’s Research Hospital , Memphis, Tennessee
          [7 ] Department of Radiation Oncology, St. Jude Children's Research Hospital , Memphis, Tennessee
          [8 ] Department of Radiation Physics, University of Texas , MD Anderson Cancer Center, Houston, Texas
          [9 ] Department of Pediatrics, Memorial Sloan Kettering Cancer Center , New York, New York
          Author notes
          Correspondence and Reprint Requests:  Wassim Chemaitilly, MD, Department of Pediatric Medicine – Division of Endocrinology, St. Jude Children’s Research Hospital, MS 737, 262 Danny Thomas Place, Memphis, Tennessee 38105. E-mail: wassim.chemaitilly@ 123456stjude.org .
          Author information
          http://orcid.org/0000-0002-7626-2336
          Article
          PMC7296130 PMC7296130 7296130 201900834
          10.1210/jc.2019-00834
          7296130
          31373627
          c0475eeb-7ef6-4306-a760-7a0b15c90439
          Copyright © 2019 Endocrine Society
          History
          : 07 April 2019
          : 29 July 2019
          Page count
          Pages: 15
          Funding
          Funded by: American Lebanese Syrian Associated Charities, DOI 10.13039/100012524;
          Funded by: National Cancer Institute, DOI 10.13039/100000054;
          Award ID: U01 CA195547
          Award ID: P30 CA021765
          Funded by: Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences;
          Award ID: TMB17316
          Funded by: Stichting Kinderen Kankervrij, DOI 10.13039/501100006244;
          Award ID: 282
          Funded by: National Institutes of Health, DOI 10.13039/100000002;
          Categories
          Clinical Research Articles
          Pituitary and Neuroendocrinology

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