Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

Abstract

Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients with craniopharyngeoma or a pituitary gland tumor were excluded. Results of all endocrine investigations, which were performed at diagnosis and during follow-up, were collected from patient charts. Multivariable logistic regression was used to study associations between demographic and tumor- and treatment-related variables and the prevalence of early endocrine disorders. Results After a median follow-up of 6.6 years, 178 CBTS (24.8%) were diagnosed with an endocrine disorder. A total of 159 CBTS (22.1%) presented with at least one endocrine disorder within the first 5 years after diagnosis. The most common endocrine disorders were growth hormone deficiency (12.5%), precocious puberty (12.2%), thyroid-stimulating hormone deficiency (9.2%), and thyroidal hypothyroidism (5.8%). The risk of hypothalamic-pituitary dysfunction (n = 138) was associated with radiotherapy (odds ratio [OR], 15.74; 95% CI, 8.72 to 28.42), younger age at diagnosis (OR, 1.09; 95% CI, 1.04 to 1.14), advanced follow-up time (OR, 1.10; 95% CI, 1.02 to 1.18), hydrocephalus at diagnosis (OR, 1.77; 95% CI, 1.09 to 2.88), and suprasellar (OR, 34.18; 95% CI, 14.74 to 79.29) and infratentorial (OR, 2.65; 95% CI, 1.48 to 4.74) tumor site. Conclusion The prevalence of early endocrine disorders among CBTS is high. The observation that 22.1% of CBTS developed at least one endocrine disorder within the first 5 years after diagnosis stresses the importance of early and regular assessment of endocrine function in CBTS who are at risk for endocrine damage.

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…HP axis dysfunction is frequently observed in survivors of central nervous system (CNS) tumors and those whose HP region was exposed to radiation (4). Data supporting associations between conventional chemotherapy and irreversible HP axis dysfunction are limited (5, 6, 7).…”

“…With a prevalence of 12.5%, GHD is the most common endocrine disorder in childhood CNS survivors even after the exclusion of patients with HP tumors (4). The prevalence is even higher in patients exposed to highdose CRT; for example, the cumulative incidence of GHD exceeded 90% at 4 years of follow-up after the treatment of medulloblastoma (11).…”

“…Patients experiencing direct HP injury related to local tumor growth or surgical resection generally present with multiple and simultaneously occurring HP disorders at the time of tumor diagnosis or shortly after surgery. In contrast, patients with radiation-induced dysfunction are diagnosed with one or multiple HP disorders often sequentially and over a period of time extending from a few months to several decades (4,11,12). Central diabetes insipidus, a common and challenging complication of tumors or surgical resections involving the HP region, does not occur as a late-effect; it will therefore not be discussed in the present summary (4).…”

“…In contrast, patients with radiation-induced dysfunction are diagnosed with one or multiple HP disorders often sequentially and over a period of time extending from a few months to several decades (4,11,12). Central diabetes insipidus, a common and challenging complication of tumors or surgical resections involving the HP region, does not occur as a late-effect; it will therefore not be discussed in the present summary (4). The risk of radiation-related HP axis dysfunction increases with the dose of radiation and the duration of follow-up (12).…”

“…The highest risk factors include tumor growth or surgery within or near the HP region, and HP radiation doses ≥18 Gy (4,12,16). Patients exposed to 10-18 Gy may also develop GHD if followed for an extended period as the risk increases in a both dose-and time-dependent fashion (17).…”