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

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.

Fig 1.

CONSORT diagram. ACTHD, adrenocorticotropic hormone deficiency; CRT, cranial radiotherapy; GHD, growth hormone deficiency; LH/FSHD, luteinizing hormone/follicle-stimulating hormone deficiency; SJLIFE, St Jude Lifetime study; TSHD, thyroid-stimulating hormone deficiency.

Fig 2.

Summary of the St Jude Lifetime (SJLIFE) study design relative to retrospective and prospective ascertainment of pituitary dysfunction. (*) Subgroup of patients participating in the After Completion of Therapy (ACT) Program initiated in 1984. IQR, interquartile range; SD, standard deviation.

Fig 3.

Relative proportions and overlap among anterior pituitary deficiencies following cranial radiotherapy. ACTHD, adrenocorticotropic hormone deficiency; GHD, growth hormone deficiency; LH/FSHD, luteinizing hormone/follicle-stimulating hormone deficiency; TSHD, thyroid-stimulating hormone deficiency.

Fig A1.

Cumulative incidence of (A) growth hormone (GH) deficiency, (B) thyroid-stimulating hormone (TSH) deficiency, (C) luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency, and (D) adrenocorticotropic hormone (ACTH) deficiency from cancer diagnosis.