Remission of tumor induced hypoglycemia and malignant hypertension with the IgF-2 inhibitor pasireotide in metastatic adrenocortical carcinoma (ACC): Remission of ACC with pasireotide

Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with a 5-year survival rate of 15%. Non-islet cell tumor-associated hypoglycemia (NICTH) due to overexpression of IgF-2 has been documented. A 40-year-old man was found apneic with hypoglycemia. Recurrent hypoglycemia was noted after injection of 50% dextrose. At the hospital, his serum glucose was <40mg/dl. His blood pressure (BP) was 199/103 mmHg. Hypoglycemia failed to respond to intravenous (IV) dextrose, glucagon, or dexamethasone, but responded to IV octreotide. His hypertension did not respond to octreotide and required six different BP drugs. CT showed a right adrenal mass directly invading the right liver lobe. He underwent complete resection. His preoperative IgF-2/Igf-1 ratio was greater 50 and normalized postoperatively. After an eight-month remission, multiple spinal and pulmonary metastases developed. Reevaluation of the pathological specimen was consistent with adrenocortical carcinoma. Metastatic disease was only partially responsive to lutetium 177 dotatate, surgery, irradiation, and six chemotherapeutic regimens. Hypoglycemia recurred, and he required six drugs to control his BP. IgF-2/IgF-1 ratio was 46. Pasireotide 0.6mg twice daily was added to pembrolizumab and mitotane. The patient had cessation of hypoglycemia and normotension off drugs. CT revealed tumor necrosis of his largest pulmonary metastasis. Remission has persisted for eight months. Therefore, utilization of SQ pasireotide for ACC may result in tumor remission including relief from paraneoplastic effects.