ESPE Abstracts

Background: Neuroblastoma (NBL) is the most common extra cranial solid tumor in children. Endocrine adverse effects after treatment for NBL have been reported of which mainly caused by treatment with 131meta-iodobenzylguanidine ([131I]MIBG) or with alkylating agents and may consist of thyroid disorders, gonadal insufficiency or short stature. Due to recent developments patients are increasingly treated with [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor that is overexpressed on neuroblastoma. However, the somatostatin receptor is also found on the cells of the anterior pituitary gland, where it regulates release of growth hormone (GH) and thyroid-stimulating hormone (TSH). Thus far no hormonal deficiencies have been reported after PRRT for NBL. We report a first case of GH and TSH deficiency after PRRT for refractory NBL.

Case: A 7 year old girl presented at the endocrine clinic with short stature. She had been treated for metastasized neuroblastoma at age 3 according to the DCOG-NBL2009 high risk protocol, including [131I]MIBG therapy, surgery and high dose chemotherapy with autologous stem cell transplantation (ASCT). Because of persistent metastatic disease she was treated with one cycle of 7400 MBq [177Lu]Lu-DOTATATE PRRT at age 4. Following PRRT the girl underwent a second ASCT for persistent bone marrow suppression, and finished treatment with anti-GD2 immunotherapy. In the course of therapy, she had received numerous (over 20) blood transfusions. As a complication of treatment she developed stage 2 chronic kidney. Additional endocrine testing revealed GH deficiency (IGF-1 < -2 SD with maximal peak in stimulation test to 14 mIU/L). GH treatment was started. Three months after GH therapy, TSH deficiency developed and thyroid hormone suppletion was started.

Discussion: Short stature after NBL treatment in this girl may be multifactorial including the high dose chemotherapy, [131I]MIBG therapy, and kidney failure. However, all these factors contributing to short stature do not result in GH deficiency. GH insufficiency has been suggested to occur in adults following treatment with PRRT. Although pituitary dysfunction caused by hyperferritinemia cannot be excluded, we hypothesize that the GH and TSH deficiency in this case are caused as a consequence of pituitary damage through binding of [177Lu]Lu-DOTATATE to the somatostatin receptors. Future studies are needed to confirm our findings.