SUN-290 - Tumor-Induced Hypoglycemia from A Pelvic Solitary Fibrous Tumor with Discordant IGF Testing

Background: Non-islet cell tumor hypoglycemia (NICTH) is a rare cause of hypoinsulinemic hypoglycemia, classically due to tumor-derived IGF-2. Typical findings include low insulin and C-peptide, suppressed ketones, and low IGF-1 from GH-axis suppression. We report an atypical case in which the clinical and tumor context fit NICTH, but the expected IGF-2 signature does not.

Case: A 49-year-old man presented with altered mental status. During this episode, glucose was 33 mg/dL (ref 70–99) with insulin < 1.0 µIU/mL (fasting ref < 25), C-peptide < 0.2 ng/mL (ref 0.8–3.1), and beta-hydroxybutyrate 0.5 mmol/L (ref < 0.6). HbA1c was 5.2%, AM cortisol 25.6 µg/dL (ref 6.0–18.4), IGF-1 25.6 ng/mL (Z = -4.65), and IGF-2 63 ng/mL (ref 180–580). CT of the chest/abdomen/pelvis showed a 14.2×10.6×11.1 cm enhancing right pelvic mass arising from the seminal vesicle without clear visceral organ involvement. Core biopsy showed monomorphic epithelioid cells with dense stromal collagen (5 mitoses/10 HPF); STAT6 was positive and RNA fusion testing identified NAB2::STAT6, confirming solitary fibrous tumor. PET showed a hypermetabolic pelvic mass with no metastatic disease.
Results/Outcome: Prednisone 25 mg daily, continuous glucose monitoring, and frequent meals/snacks were initiated as temporizing measures to prevent recurrent fasting hypoglycemic events while awaiting definitive tumor-directed therapy. Prednisone was tapered to 20 mg then 15 mg daily. After particle embolization, the patient had stable glucose and was able to quickly taper prednisone off within 4 weeks. He has since been off prednisone with continued symptom resolution. Surgical resection is planned.

Discussion: Low IGF-1 with hypoinsulinemic hypoglycemia and relative hypoketonemia supports IGF-mediated NICTH physiology despite low total IGF-2. The IGF-2:IGF-1 ratio was approximately 2.5; because ratios >10 strongly support NICTH, this low ratio created diagnostic discordance. Potential explanations include routine assay under-detection of tumor-derived IGF-2, reduced IGF binding proteins (IGFBP-3/ALS) increasing IGF activity without elevating total IGF-2, and biologic variability with illness/nutrition. Alternative causes of hypoinsulinemic hypoglycemia include unrecognized hypoglycemic drug exposure, illness/sepsis, hepatic or renal failure, or other endocrine deficiency; however, symptom improvement and ability to taper steroid after tumor embolization favor a tumor-mediated process.

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