MON-512 management of an adrenal cortical carcinoma induced non-islet cell tumor hypoglycemia: a case report

Abstract Disclosure: Y. Tang: None. E. Jeong: None. A. Herrera Chancay: None. S. Byun: None. S. Waghwala: None. L. Jia: None. J. Abramowitz: None. O. Hamidi: None. S. Ali: None. Background: Non-islet cell tumor hypoglycemia (NITCH) is a rare but critical condition that significantly worsens the prognosis of underlying malignancies. Furthermore, NITCH caused by adrenal cortical carcinoma (ACC) is even rarer. To date, no curative treatment of non-operable NITCH has been reported. We describe a case of ACC-induced NITCH who was refractory to multiple new hypoglycemia and antineoplastic managements. Case: A 62-year-old woman presented with severe hypoglycemia 2 years after the diagnosis of ACC. Her ACC initially manifested as new-onset diabetes, unintentional weight loss, and excessive weakness, followed by imaging with CT scan detecting a heterogenous 13x10x11.4 cm right adrenal mass. Hormonal workup showed elevated cortisol, testosterone and DHEA-S levels. Tumor resection was pursued immediately, and pathology reported ACC at stage pT3N1 with extensive tumor necrosis, mitotic rate of 24/50 HP, and Ki67 of 20-30%. She was started on adjuvant mitotane, and chemotherapy (cisplatin, etoposide, and doxorubicin) which induced cardiomyopathy. At 6-month postoperative monitoring, she developed local recurrent ACC and lung metastases. Systemic regimen was switched to pembrolizumab. Local ACC recurrence was treated with radiation therapy. Due to disease progression, she was switched to olaparib/ivosidenib. Osilodrostat was initiated for Cushing syndrome. As interval imaging showed tumor progression, she was also noted to have new onset symptomatic hypoglycemia, with fasting serum glucose 38mg/dl. Concomitant insulin, proinsulin and c-peptide levels were low. Further hypoglycemia workup revealed elevated IGF-II (> 1,315 ng/ml, ref <967ng/ml), low-normal IGF-1 (34ng/ml, Z-score -1.96), and significantly elevated IGF-II: IGF1 ratio (>38), confirming IGF-2 mediated hypoglycemia and diagnosis of NITCH. Patient had recurrent severe hypoglycemic episodes, which were refractory to increasing carbohydrate intake, high-dose prednisone, and octreotide. She was admitted to the ICU for hypoglycemia management with IV dextrose 50 and IV glucagon drip. She also received pasireotide 60mg and diazoxide 5mg/kg every 8 hours. Her hospital course was complicated by volume overload despite aggressive diuresis, which limited IV drip rates. Cabozantinib was added to treat ACC but quickly discontinued due to pancytopenia. Upon applying for alpelisib approval, her clinical status rapidly declined, and she died after 3 months of NITCH diagnosis. Discussion: IGF-II production in the recurrent/metastatic ACC is extremely rare. IGF2-mediated hypoglycemia was refractory to numerous therapeutic interventions, including paseriotide, pembrolizumab, olaparib, ivosidenib, and cabozantinib. This case emphasizes rare manifestations of metastatic ACC and limitations of existing medical therapies for NITCH. Presentation: Monday, July 14, 2025