SUN-572 - When Insulin Isn'T the Culprit: A Case of IGF-2-Mediated Non-Islet Cell Tumor Hypoglycemia

Background:
Non-islet cell tumor hypoglycemia (NICTH) is a rare, potentially life-threatening paraneoplastic syndrome typically mediated by excess of incompletely processed or high-molecular-weight insulin-like growth factor 2 (IGF 2), leading to recurrent hypoglycemia in patients without hyperinsulinemia. Diagnosis is often delayed, particularly in patients with advanced or occult malignancy. While surgical resection of the underlying malignancy is optimal, it is often not feasible, necessitating medical management. Ideal medical management is unclear.

Case Description:
A 43-year-old man with no prior medical history presented with abdominal pain and significant unintentional weight loss. Imaging demonstrated peritoneal carcinomatosis and multiple hepatic metastases without an identifiable primary tumor. Omental biopsy revealed poorly differentiated adenocarcinoma with high-grade features. Alpha fetoprotein and CA 19-9 were markedly elevated. During hospitalization, he developed recurrent, severe fasting hypoglycemia multiple times daily, despite adequate oral intake and continuous dextrose infusion. Critical sampling during a spontaneous episode of hypoglycemia with blood sugar 35mg/dL showed suppressed insulin, C peptide, proinsulin, and beta hydroxybutyrate, with markedly reduced IGF 1 (19ng/mL) and a normal IGF 2 level (303 ng/mL), resulting in an elevated IGF 2/IGF 1 ratio of 15.9. These findings were diagnostic of NICTH. Hypoglycemia was initially refractory to dextrose infusion alone and initiation of glucocorticoid therapy with prednisone up to 10mg three times daily. Adjunctive agents such as glucagon or recombinant human growth hormone were considered, but glycemic control was successfully achieved with dose escalation of prednisone to 20mg three times daily in the setting of frequent carbohydrate-rich meals.

Discussion:
This case highlights IGF-2-mediated NICTH in the setting of metastatic adenocarcinoma of unknown primary origin and underscores the diagnostic importance of the IGF-2/IGF-1 ratio, even when absolute IGF-2 levels are normal. Early recognition and glucocorticoid therapy are critical for effective management when tumor resection is not feasible. High doses of glucocorticoids may be necessary to achieve control in refractory cases.

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