Endocrine Complications and Components of the Metabolic Syndrome in Survivors of Childhood Malignant Non-Brain Solid Tumors

Abstract

Background/Aims: The substantial improvement in survival of children with cancer has been achieved at the cost of late effects.We aimed toevaluate the endocrine outcome in survivors of childhood non-brain malignant solid tumors (NBMST). Methods: We performed aretrospective medical record review for medical history, clinical and laboratory data of survivors (n = 139) followed at the endocrine clinic of a tertiary medical center. Outcome measures were frequency and types of endocrine dysfunction and components of the metabolic syndrome. Results: Median follow-up time was 9.0 years (range 1.2-29.5 years). At least one endocrine abnormality was found in 44 patients (31.7%). Abnormalities included hypogonadism (11.5%), hypothyroidism (9.4%), short stature (9.4%), growth hormone deficiency (8.6%) and components of the metabolic syndrome (15.1%). Height SDS decreased significantly (p = 0.004) during follow-up, whereas body mass index SDS tended to increase. On logistic regression analysis, treatment with cranial irradiation (p = 0.003), local radiation (p = 0.042), or bone marrow transplantation (p = 0.0001), and older age at last visit (p < 0.001) were associated with a significantly higher hazard of an endocrinopathy. Conclusions: The high rate of late endocrine dysfunction among survivors of childhood NBMST highlights the need to optimize the follow-up at the late-effects clinics to identify endocrine problems and allow early and effective intervention.

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

“…A relatively high incidence (24%) of ACTHD was reported in a study of CCS treated with HSCT, but this was likely overestimated by the use of testing modalities that are subject to significant variability (85). ACTHD has also been reported in a small number of CCS treated with radiotherapy for non-brain solid tumors of the head (30,32,76). Hypophysitis subsequent to the use of ipilimumab may also result in ACTHD (10).…”

“…The clinical relevance of the subtle laboratory findings upon which these diagnoses were based is questionable (83). TSHD has also been described in a small number of patients treated with radiotherapy for retinoblastoma and other non-brain solid tumors of the head (29,32,76). Hypophysitis subsequent to the use of ipilimumab may also result in TSHD (10).…”

“…Its cumulative incidence among CCS of embryonal tumors of the CNS treated with cranial and cranio-spinal irradiation was 65 ± 7% by 4 years of follow-up (11). With a prevalence of 10%, primary hypothyroidism is also among the most common endocrine complications reported in survivors of malignant extra-cranial solid tumors (76).…”

“…Male CCS treated with HSCT are generally able to retain normal Leydig cell function if they were conditioned for transplant using standard doses of cyclophosphamide or TBI if the cumulative testicular radiotherapy dose was <20 Gy (7,72,90,94,121). Leydig cell failure has also been reported in survivors of pediatric Hodgkin's lymphoma (122) and of various solid tumors (76,123) due to treatment with high-dose alkylating agents and/or testicular exposure to radiotherapy.…”

“…Diabetes and insulin resistance do not seem to be related to obesity, as measured by BMI, in this population (190,191); their pathophysiology seems to involve abnormal body fat distribution and possibly pancreatic islet cell injury due to TBI (192,193). Survivors of solid tumors requiring treatment with abdominal radiotherapy may also have a higher risk of glucose intolerance and diabetes mellitus (76,194,195,196,197).…”