Endocrinology Fellow Ochsner Clinic Foundation Pensacola, Florida, United States
Introduction : Non-islet cell tumor hypoglycemia (NICTH) is an infrequent yet severe paraneoplastic syndrome, marked by the secretion of high molecular weight insulin-like growth factor-2 (IGF-2) from tumors, resulting in hypoglycemia through an insulin-independent mechanism. While complete tumor resection is curative, practical challenges often delay or render surgery unfeasible.Medical management, particularly with glucocorticoids, becomes essential for patients who are unsuitable for surgery due to comorbidities or failure to localize a tumor.
Case(s) Description : A 66-year-old male with recurrent hypoglycemic episodes, was evaluated by the inpatient endocrine service at Ochsner Medical Center. Despite no history of gastric bypass, adrenal insufficiency, or diabetes and no use of insulin or oral hypoglycemic agents, he was having frequent episodes of fasting hypoglycemia. The timing of hypoglycemia was concerning for excess endogenous insulin production along with the concern for delayed insulin clearance in the setting of his end-stage renal disease (ESRD). Inpatient observed fast revealed abnormal labs in the early morning consistent with an "insulin-like" process with undetectable insulin levels, low normal C-peptide, low beta-hydroxybutyrate and confirmed serum hypoglycemia. Additional labs showed IGF-2 to IGF-1 ratio of 10:1 consistent with a diagnosis of NICTH. Medical management was started with prednisone and nightly cornstarch, resulting in stable fasting blood glucose levels within 24 hours. Imaging failed to localize a tumor so pancreastatin and 5-HIAA labs were checked with both being elevated pointing towards a neuroendocrine tumor as the source. Medical management continued with plans for outpatient Cu-Dotatate PET/CT and oncology/neuroendocrine specialty referral, but the patient died from unrelated complications during a subsequent admission prior to being seen.
Discussion : Hypoglycemia is uncommon outside of the diabetic population. When NICTH is suspected further evaluation is needed with appropriate labs and imaging. While the ideal management of NICTH involves surgical intervention, medical management alone can be efficacious when tumor localization is challenging or in patients where surgery is not feasible. Beyond glucocorticoids and corn starch, second-line therapies, such as chemotherapy and recombinant growth hormone, may be considered. Importantly, it is highlighted that therapies used in the treatment of insulinoma, like diazoxide and octreotide have no role in NICTH due to its insulin-independent mechanism. Understanding the diverse aspects of NICTH is crucial for effective clinical management and patient outcomes.
