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

J Clin Endocrinol Metab. 2019 Dec 1;104(12):6101-6115. doi: 10.1210/jc.2019-00834.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenocorticotropic Hormone / deficiency
  • Adult
  • Aged
  • Cancer Survivors / statistics & numerical data*
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / epidemiology
  • Central Nervous System Neoplasms / radiotherapy
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cranial Irradiation / adverse effects
  • Cranial Irradiation / statistics & numerical data
  • Cross-Sectional Studies
  • Female
  • Follicle Stimulating Hormone / deficiency
  • Growth Disorders / epidemiology
  • Growth Disorders / etiology
  • Human Growth Hormone / deficiency
  • Humans
  • Hypothalamic Diseases* / diagnosis
  • Hypothalamic Diseases* / epidemiology
  • Hypothalamic Diseases* / etiology
  • Hypothyroidism / epidemiology
  • Hypothyroidism / etiology
  • Infant
  • Infant, Newborn
  • Luteinizing Hormone / deficiency
  • Male
  • Middle Aged
  • Pituitary Diseases* / diagnosis
  • Pituitary Diseases* / epidemiology
  • Pituitary Diseases* / etiology
  • Prevalence
  • Prognosis
  • Puberty, Precocious / epidemiology
  • Puberty, Precocious / etiology
  • Retrospective Studies
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Human Growth Hormone
  • Adrenocorticotropic Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone