SUN-LB059 A Rare Case Of Hypoglycemia Secondary To Proinsulin-Intermediate Secreting Tumor

Abstract

IntroductionPancreatic neuroendocrine tumors (PNETs) that solely produce proinsulin (PI) manifesting with hypoglycemia and normal or low serum insulin (IN) levels are rare. Des 64-65 is a PI intermediate. We report a novel case of hypoglycemia secondary to a possible PI intermediate proinsulinoma. Case descriptionA 60-year-old diabetes educator presented with two years of double vision, light-headedness, and paresthesias aggravated by stress and alleviated with meals. She had a history of hypothyroidism treated with levothyroxine. Fingerstick glucose with symptoms was 46 (60-140 mg/dl). Physical examination was unremarkable. A fasting hypoglycemia test confirmed serum glucose of 47 mg/dl after 16 hours. Serum IN was 2.2 (3.0-25.0uIU/ml), C-peptide 1.1 (0.8-3.0ng/ml), and PI 262.4 (≤ 18.8 pmol/L). PI was measured by radioimmunoassay (RIA) using a polyclonal goat antibody (AB) with specificity for the B-C junction which does not distinguish between PI and its intermediate forms. IN autoantibodies were negative. β-hydroxybutyrate was ≤ 0.28 (0.32 mmol/L). IN secretagogue panel was negative. Endoscopic ultrasound revealed a 14 x 8 mm isoechoic mass in the pancreatic tail. Fine needle aspirate was positive for synaptophysin. The Ki-67 index was 3%. Immunohistochemistry (IHC) showed low IN and PI intensity. GS-9A8, a monoclonal AB from the Developmental Studies Hybridoma Bank at the University of Iowa, was used in the IHC. This antibody binds to the B-C junction of human and monkey proinsulin and stains only intact, non-processed PI found in the immature secretory granules of islet beta-cells. It does not cross-react to insulin or C-peptide. Positron emission tomography did not reveal hypermetabolic activity or distant metastases. Robotic distal pancreatectomy confirmed a well-differentiated PNET that was low intensity for IN and PI on IHC. Post-operatively, her glucose was 117 mg/dl, PI 8.8 pmol/L, IN 3 uIU/ml, C-peptide 0.8 ng/ml. She remains asymptomatic at 6 month follow up. DiscussionHypoglycemia in the setting of a pancreatic mass is usually due to IN producing PNETs. PI secreting tumors are a rare entity. PI acts on the IN receptor demonstrating a weak hypoglycemic effect. Our case showed low intensity IHC for IN and PI, with low serum IN and elevated serum PI. The low intensity IN and PI IHC using a monoclonal AB that stains only intact, non-processed PI, associated with an elevated serum PI level using an RIA that employs a polyclonal goat AB with specificity for the B-C junction and which does not distinguish between PI and its intermediate forms, suggests that the tumor was possibly producing a PI intermediate with an intact B-C junction, likely des 64-65 PI. Low intensity IN and PI IHC would suggest unregulated release with decreased intracellular storage of PI. PI or PI intermediate secreting PNET must be considered when evaluating hypoglycemia. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.