An ACTH-Producing Neuroendocrine Tumor: Clinical Course of Multidisciplinary Therapy Including Peptide Receptor Radionuclide Therapy - A Case Report.

INTRODUCTION: Clinical experiences of peptide receptor radionuclide therapy (PRRT) in patients with adrenocorticotropic hormone (ACTH) producing neuroendocrine tumor (NET) were extremely rare. CASE PRESENTATION: A 60-year-old woman with hypertension, lower-extremity edema, hypoalbuminemia, hypokalemia, and multiple hepatic tumors was hospitalized for further examination and treatment. Endocrine testing detected excessive levels of ACTH and cortisol in her blood. Pathohistological examination revealed the hepatic lesions to be ACTH-positive grade 2 NETs (G2). A diagnosis of ectopic ACTH-producing NET was made. The patient was initially treated with the 11-hydroxylase inhibitor, metyrapone, to control hypercortisolemia and the long-acting somatostatin analog, lanreotide. Simultaneously, everolimus was continued for about 1 year. Subsequently, hepatic tumors were surgically resected, leading to successful and rapid normalization of ACTH secretion and resolution of hypercortisolemia. However, the disease relapsed and presented with multiple hepatic masses and increased ACTH 18 months after surgery. As sunitinib and subsequent streptozocin chemotherapy failed to control the disease, PRRT with (177)Lu-DOTATATE was performed. ACTH levels increased after initiation of PRRT, and clinical manifestations, such as pigmentation, hypertension, and hyperglycemia, were remarkable. The patient was treated with antihypertensive and antidiabetic agents, and required an increased dose of metyrapone and addition of the cortisol biosynthesis inhibitor, osilodrostat. After four cycles of PRRT, the hepatic tumors showed a remarkable reduction in size with normalization of ACTH level and withdrawal of cortisol synthesis inhibitors. CONCLUSION: Although PRRT was effective, we should consider the occurrence of hormonal crisis during the therapy. Due to the rarity and complexity of hormone-producing tumors, cooperation between medical oncologists and endocrinologists is important for patient management.