SUN-340 Doege-Potter Syndrome: The Case of a Non-Islet Cell Tumor Hypoglycemia

Abstract K.N. Sheikh: None. A. Mody: None. A. Haynes: None. P.V. Kumar: None. Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome which occurs as a result of tumoral overproduction of an incompletely processed precursor of insulin-like growth factor II (IGF-II), also known as big-IGF-II or high molecular weight IGF-II. The hypoglycemia is non-insulin mediated. Here we present the case of a 66-year-old male with no relevant past medical history who presented to the emergency department due to two weeks of increasing confusion and lethargy. Serum glucose was noted to be 34 mg/dL. Upon administration of dextrose, the patient’s symptoms immediately improved. The patient was discharged on glucocorticoids by the hospitalist team. Outpatient evaluation revealed a serum glucose of 48 mg/dL, a low insulin level <0.4 uIU/mL (3-25uIU/mL), a low C-peptide level 0.3 ng/mL (0.8-3.5 ng/mL), and a low proinsulin level 3.5 pmol/L (<8.0 pmol/L). Sulfonylurea panel was negative. Outpatient evaluation revealed an elevated IGF-II level of 1199 ng/mL (267-616 ng/mL) and a low IGF-1 level of 31 ng/mL (55-165 ng/mL). CT abdomen and pelvis demonstrated an approximately 21 cm heterogeneous, complex mass in the lower abdomen and pelvis. Biopsy of the mass demonstrated a solitary fibrous tumor (SFT) with expression of STAT-6 and beta-catenin. The patient underwent surgical resection of the mass, and his blood glucose levels normalized in the immediate postoperative period. NICTH is characterized by an IGF-II:IGF-1 ratio greater than 10:1. In our patient, the IGF-II:IGF-1 ratio was 39:1. Doege-Potter syndrome occurs when the production of big IGF-II is specifically from SFTs. SFTs are associated with a NAB2-STAT6 fusion gene that leads to the dysregulation of big-IGF-II. Excess big-IGF-II can bind to both the insulin receptor and the IGF-II receptor. This drives the internalization of glucose into the tissue and inhibits gluconeogenesis, resulting in refractory hypoglycemia. Glucocorticoid therapy has been demonstrated to be one of the most effective therapies for management of hypoglycemia. Complete surgical resection is the only definitive treatment of NICTH. This highlights the importance of detecting these tumors as early as possible before the occurrence of metastases. Sunday, June 2, 2024