SAT-483 - Non-Islet Cell Tumor Hypoglycemia Secondary to an IGF-2-Secreting Adrenocortical Carcinoma

Background
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that may be functionally active, secreting cortisol or androgens even in the absence of overt clinical signs. There have also been reports of cases of ACC secreting IGF-2 leading to non-Islet cell tumor hypoglycemia (NICTH). This paraneoplastic phenomenon is characterized by hypoglycemia with suppressed insulin and IGF-1 levels, and an elevated IGF-2: IGF-1ratio.
Case Presentation
A 60-year-old woman with hypertension presented after a syncopal episode associated with a serum glucose of 37 mg/dL. She reported a one-year history of abdominal distension, 20-pound weight loss, and night sweats. Examination revealed a palpable abdominal mass. CT scan showed a 19-cm heterogeneous left upper abdominal mass with an unclear origin. She had no clinical signs of Cushing’s syndrome or hyperandrogenism.
During a hypoglycemic episode (glucose 29 mg/dL), insulin, C-peptide, and acetone were suppressed. IGF-2 was 262 ng/mL (267-616 ng/mL) with undetectable IGF-1, yielding a markedly elevated IGF-2:IGF-1 ratio. Biopsy of the abdominal mass revealed a poorly differentiated sarcomatous carcinoma with neuroendocrine features.
Her hypoglycemia was treated with 10% dextrose infusion and total parenteral nutrition, and she eventually underwent extensive surgical resection, including tumor excision, radical left nephrectomy, partial pancreatectomy, and cholecystectomy. The tumor weighed 3,509 g and measured 23 cm. Tissue pathology showed a poorly differentiated carcinosarcoma with a high Ki-67 index (10-15%); the pancreas, kidney, and spleen were uninvolved. The slides were sent to NIH for additional review, which showed atypical epithelioid neoplasm consistent with high grade ACC. Postoperatively, hypoglycemia resolved, and the IGF-2:IGF-1 ratio declined to 8.
She returned 6 weeks later with widespread metastases, was felt to be not a candidate for chemotherapy, and succumbed to her disease.
Conclusion
This case highlights IGF-2–mediated NICTH as a rare endocrine manifestation of ACC. To our knowledge, this is the 10th case to have been reported since the development of IGF-2 assay in 1987. Suppressed insulin levels and an elevated IGF-2:IGF-1 ratio were keys to the biochemical diagnosis. Prior cases have shown IGF-2 levels to be high, normal or low; however, the consistent finding was an elevated IGF-2:IGF-1 ratio>10. While tumor resection can rapidly correct hypoglycemia, early endocrine recognition is critical for metabolic stabilization and multidisciplinary management.

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