MON-090 - Malignant Insulinoma Complicated by Refractory Hypoglycemia

Context: Insulinomas are rare neuroendocrine tumors that can be challenging due to metastases and severe hypoglycemia. We describe the management of a patient with refractory hypoglycemia due to metastatic insulinoma.

Case Description: A 60-year-old male presented to the hospital with a gastrointestinal bleed. Evaluation revealed a pancreatic head mass causing gastric variceal bleeding and encasing the surrounding vasculature. Biopsy confirmed a WHO Grade 2 Neuroendocrine Tumor (Ki67 8%, Stage cT3N1M0). PET-DOTATATE confirmed the absence of metastases. He underwent neoadjuvant chemotherapy with Temozolomide (following Capecitabine intolerance) and completed 3 rounds of Lu 177 dotatate peptide receptor radionuclide therapy. Despite initial hyperglycemia (HbA1c 7.3%) , the patient’s disease progressed over two years and he developed severe, refractory hypoglycemia. Fasting labs showed glucose 44 mg/dL, insulin 88.2 uUI/mL (2.6-24.9) , C-peptide 11.4 ng/mL (1.1-1.4), HbA1c 4.9% He was started on everolimus, diazoxide 50mg TID, and cornstarch at bedtime; however, he was hospitalized for severe hypoglycemia the following week. Glucose 40 mg/dL, insulin 132 uUI/mL and proinsulin > 700 pM (3.6-22). He was hospitalized for >1 month for refractory hypoglycemia despite continuation of everolimus/diazoxide and addition of octreotide. He underwent transcatheter arterial chemoembolization (TACE) to control insulin secretion. Despite this he remained dependent on continuous dextrose at rates of 15 to 20 gm/hour due to poor appetite. A discussion involving endocrinology, oncology, critical care, and the patient focused on quality-of-life goals. He was started on overnight tube feeds with daytime boluses to facilitate discharge and long-term home management. He continued medical therapy and showed significant glycemic improvements 3 weeks after TACE and was able to discontinue octreotide and lower diazoxide

Conclusions: Refractory hypoglycemia in malignant insulinoma can be challenging to manage.

While diazoxide and somatostatin analogs (SSAs) like Octreotide are first-line medical therapies, the response to SSAs can be unpredictable; some patients experience paradoxical worsening of hypoglycemia if the tumor predominantly expresses SSTR5 over SSTR2, or if glucagon/growth hormone suppression outweighs insulin suppression. Second-generation SSAs like Pasireotide (SSTR5 >>2) have shown promise in refractory cases as has everolimus. For unresectable and medically refractory disease, interventions such as TACE or Yttrium-90 radioembolization are increasingly documented as effective "bridge" therapies to achieve cytoreduction and glycemic stability, and as illustrated in this case, nutritional interventions including continuous dextrose or cyclic enteral feeding become the cornerstone of maintaining glycemia while pursuing more definitive therapies.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*