ESPE Yearbook of Paediatric Endocrinology

rakeshkgyl@gmail.com J Pediatr Hematol Oncol. 2022; 44: e469-e473. PMID: 34054040.

Brief Summary: This monocentric, retrospective study investigated adrenal insufficiency (AI) prevalence in a large group of children with brain tumors (BT, 398 patients) and children treated with hematopoietic cell transplantation (HCT, 268 patients). AI was diagnosed in 14 BT patients (27.4% of the 51 tested) and 14 HCT recipients (21.2% of the 66 tested).

Children with BT and children undergoing HCT may develop central AI due to exogenous glucocorticoids, and/or direct damage of the hypothalamic-pituitary (HP) area induced by the tumor location itself, surgery, and/or radiotherapy. In this study, low-dose ACTH test (1 mcg cosyntropin intravenously) was used in cases of suspected central AI. High-dose ACTH test (15 mcg/kg cosyntropin intravenously, maximum 250 mcg) was performed to diagnose primary AI. In this study, the institutional medical records were searched between 2006 and 2017. ACTH stimulation testing was performed in 51/398 (12.8%) children with BT and in 66/268 (24.6%) HCT recipients, and AI was defined as peak serum cortisol <18 mcg/dL

AI was diagnosed in 14/51 (27.4%) of BT patients tested. There was a higher rate of AI in patients with direct involvement of the hypothalamic-pituitary-adrenal (HPA) axis by tumor (36% vs 21%), in those undergoing surgery involving the hypothalamic-pituitary (HP) region (50% vs 23%) and in those who received ≥30Gy dose of cranial radiotherapy (32% vs 11%). Maintenance and stress-dose glucocorticoids were recommended in 81% of patients with inadequate response at ACTH test, stress-dosing alone was recommended in 19%.

AI was diagnosed in 14/66 (21.2%) of HCT recipients tested. In this group, 9/66 patients had received TBI. The most common indication for testing (56% patients) was exogenous glucocorticoid exposure. The rate of AI was higher in patients with graft-versus-host disease (36% vs 12.5%), who frequently receive exogenous steroids. Maintenance and stress-dose glucocorticoids were recommended in 80% of patients with inadequate response at ACTH test, while stress-dosing alone was indicated in 20%.

The prevalence of iatrogenic AI in children with cancer is probably underestimated and can be life-threatening. Among children with BT, AI is more often diagnosed in patients with primary lesion involving the HP region, in those who received cranial radiotherapy, and those with other pituitary deficiencies. These observations emphasize the importance of testing for AI all patients carrying these risk factors, in particular before any surgical procedure or general anesthesia, due to the risk of acute adrenal failure. For this purpose, a close collaboration between pediatric hematology-oncology and endocrinology specialists is advocated. Strengths of the study are the large sample of BT and HCT patients. In this study, only a minority of patients underwent ACTH testing so possibly many other cases were missed. Other limitations are its retrospective nature and the lack of repeated tests to distinguish patients who had temporary AI due HPA axis suppression related to prolonged steroid treatment.

The most common etiology of AI was adrenal suppression from exogenous glucocorticoids. One patient had primary AI related to MIRAGE syndrome, and another patient developed primary AI following bilateral adrenalectomy for neuroblastoma.