Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by tumor overproduction of incompletely processed insulin-like growth factor-2 (IGF-2), which exerts insulin-like effects and suppresses counter-regulatory responses. Gastrointestinal stromal tumors (GISTs) are an uncommon cause. This report describes a patient with metastatic GIST presenting with severe recurrent hypoglycemia, emphasizing diagnostic reasoning in the absence of IGF-2 testing.

A 64-year-old Chinese-Filipino man with metastatic GIST and peritoneal carcinomatosis, status post bowel resection (2011), had been treated with imatinib (2011–2024), sunitinib (June 2024–April 2025), and regorafenib (April–June 2025). One hour prior to admission, he was noted to be unresponsive. Capillary blood glucose (CBG) on arrival was less than 20 mg/dL. He had no diabetes or hypoglycemic medication use. A hypoglycemia work-up was performed at a CBG of 52 mg/dL.

Serum glucose was 41 mg/dL with markedly suppressed insulin (0.20 µU/mL) and C-peptide (0.10 ng/mL). IGF-1 was low at 26.06 ng/mL, while cortisol obtained at 2:00 PM was 10.9 µg/dL, appropriate for the sampling time, excluding adrenal insufficiency. Whipple’s triad was satisfied. Although IGF-2 assay was unavailable locally, the biochemical pattern and clinical setting strongly suggested IGF-2–mediated NICTH. FDG-PET/CT demonstrated progressive peritoneal carcinomatosis with multiple FDG-avid nodular masses (largest 9.0 × 5.8 × 5.5 cm, SUVmax 19.3). Hypoglycemia was successfully managed with intravenous dextrose, frequent carbohydrate-rich meals, and dexamethasone 4 mg every 12 hours. Surgical debulking was deferred due to diffuse metastases.

NICTH should be considered in any non-diabetic patient with recurrent fasting hypoglycemia and suppressed insulin and C-peptide levels in the context of a solid tumor. In resource-limited settings, characteristic biochemical and clinical features can establish the diagnosis even without IGF-2 measurement. Glucocorticoid therapy provides effective palliation by reducing IGF-2 activity and improving glucose homeostasis. This case underscores the critical role of clinical judgment in recognizing paraneoplastic endocrine disorders when diagnostic assays are unavailable.