Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study

J Clin Oncol. 2015 Feb 10;33(5):492-500. doi: 10.1200/JCO.2014.56.7933. Epub 2015 Jan 5.

Abstract

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.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenocorticotropic Hormone / deficiency
  • Adult
  • Bone Density
  • Child
  • Cranial Irradiation / adverse effects*
  • Energy Metabolism
  • Exercise Tolerance
  • Female
  • Follicle Stimulating Hormone / deficiency
  • Follow-Up Studies
  • Human Growth Hormone / deficiency
  • Humans
  • Hypopituitarism / etiology*
  • Hypopituitarism / metabolism*
  • Hypopituitarism / physiopathology
  • Hypopituitarism / therapy
  • Incidence
  • Luteinizing Hormone / deficiency
  • Male
  • Middle Aged
  • Muscle Weakness
  • Neoplasms / radiotherapy*
  • Physical Fitness
  • Pituitary Gland, Anterior / metabolism*
  • Pituitary Gland, Anterior / radiation effects*
  • Prevalence
  • Radiotherapy Dosage
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Survivors
  • Tennessee / epidemiology
  • Thyrotropin / deficiency
  • Time Factors
  • Young Adult

Substances

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