Long term endocrine sequelae of childhood cancer survivors

Abstract

Background: Newer multimodality therapeutic interventions have resulted in dramatic survival rates in childhood cancers. However diverse treatment related morbidities affect the long term survivors. An Endocrine complication comprises 20-40% of these morbidities and affects the hypothalamic pituitary axis, growth, pubertal progression, fertility, bone health and glucose homeostasis.

Objectives: The aim of our study was to enumerate and evaluate the frequency of endocrine complications arising as a late effect of treatment in childhood cancer survivors. Risk factors likely to be associated with these complications were also evaluated.

Methodology: Retrospective analysis of medical records from the Long Term Endocrine Follow up clinic in the Department of Paediatrics and Adolescent Medicine of Queen Mary Hospital was done. Patients with a primary diagnosis of Cancer and Langerhans cell histiocytosis with endocrine sequelae arising from various treatment modalities who have survived 5 years after diagnosis were included in the study. Those who had endocrine complications arising from various treatment modalities for Thalassemia’s, Immunodeficiency’s were excluded from the study

Results: 135 cases were included in the study and 27 were excluded. Leukemia and Brain tumor survivors were the majority accounting for 40% and 26.67% respectively. ALL formed majority of leukemia survivors, Medulloblastoma survivors accounted for 50% of brain tumor survivors. Most common endocrine problem was Hypogonadism in 51.1% of cases, followed by growth disturbances in 40%, Thyroid dysfunction in 23% and Hyperlipidemias in 18.5%. Pubertal problems, Central Diabetes Insipidus, Adrenal insufficiency, Obesity, Altered glucose homeostasis were rest of the problems in small frequencies. PHGN (Primary Hypogonadism) was present in 91.3% and mostly in prepubertal males. PHGN was statistically associated with Leukemia survivors with OR-2.06 (1.02- 4.15), p value 0.04. The risk factors associated were exposure to alkylating agents, radiotherapy, TBI prior to transplant. SHGN (Secondary HGN) was statistically associated with Brain tumor survivor OR - 15.8 (1.7-140.5), p value 0.013. Cranial irradiation was the major risk for SHGN. PGV (Poor growth velocity) was the major growth problem.GHD (Growth Hormone Deficiency) had a highly significant association with Brain tumors (p value ˂ 0.0001), and significantly associated when all 3 modalities of treatment given together (p value 0.01). Risk factors for GHD were cranial radiotherapy, exposure to cyclophosphamide and TBI. PH (Primary Hypothyroidism) had highly significant association with craniospinal radiotherapy (p value ˂ 0.0001), and significantly associated with brain tumors. Similar results were observed in patients of CH (Central Hypothyroidism).

Hyperlipidemias were present in 18% with no statistical correlation with the type of cancer. Brain tumor survivors had a significant association of GHD, PH, CH, SHGN and CDI. Leukemia survivors had significant association with GHD and PHGN.

Conclusions: Endocrine problems are frequent manifestations of late effects of cancer related treatments. Early detection and intervention of these potentially treatable problems could be done through structured long term surveillance. Increasing awareness among health care professionals to anticipate problems in suspected patients and education of patients would optimize health care and quality of life.