(CSEMP019) A RARE CASE OF NON-ISLET CELL TUMOUR HYPOGLYCEMIA FROM A SOLITARY FIBROUS LUNG TUMOUR

Abstract:

Background: Non-islet-cell tumour hypoglycemia (NICTH) is a paraneoplastic syndrome caused by high molecular weight (“big”) IGF-II production from both benign and malignant tumours. Although rare, NICTH is important to identify because treatment differs from other causes of hypoglycemia. In this case report, we highlight the clinical presentation, pathophysiology, and treatment of NICTH caused by a solitary fibrous tumour, also known as Doege-Potter syndrome.

Case: An 89-year-old woman, with a history of CHF and diet-controlled T2DM, presents to hospital with increased shortness of breath, weight loss and fatigue. She was recently diagnosed with a 13 cm biopsy-proven fibrous tumour in the right hemithorax, which is now causing hypoxia. Point-of-care glucose checks in hospital reveal daytime and overnight hypoglycemia (2.3-3.3 mmol/L) associated with fatigue, nausea and diaphoresis. Her symptoms improve with correction of hypoglycemia. Further workup yields a serum glucose level of 2.1 (4-10 mmol/L), C-peptide 67 (370-1470 pmol/L), insulin < 7 (18-173 pmol/L), beta-hydroxybutyrate < 0.1 mmol/L, and IGF-I of 35 (17-167 mcg/L). Glucagon administration results in a glucose rise from 2.9 mmol/L to 4.0 mmol/L (>1.4 mmol/L). The IGF-II assay is unavailable at our center (n.b. a ratio of IGF-II:IGF-I greater than 3:1 is suggestive of NICTH). Given her clinical presentation and biochemical findings, we make a presumptive diagnosis of Doege-Potter syndrome.

Results: With dietary changes and initiation of dexamethasone 6mg p.o. daily, both daytime and overnight hypoglycemic episodes resolve and she is successfully discharged from hospital. She is not a candidate for surgical tumour resection, and is awaiting radiation treatment while continuing on high dose steroid therapy and use of intranasal glucagon as needed.

Discussion: Recognition of NICTH is important in the treatment and prevention of hypoglycemic episodes. NICTH from Doege-Potter syndrome is associated with the NAB2-STAT6 fusion gene, which drives big IGF-II production. This IGF-II causes hypoglycemia through activating the IGF-I, IGF-II and insulin receptors to reduce growth hormone release, increase peripheral glucose uptake, as well as suppress gluconeogenesis, glycogenolysis and glucagon secretion. Although the definitive treatment of NICTH is tumour resection, medical therapy may be required to bridge to surgery and for non-surgical candidates. Our case aligns with previous reports demonstrating that treatment with high dose steroids equivalent to prednisone >20mg is effective at resolving hypoglycemia. Other treatments include recombinant human growth hormone and glucagon infusion. Somatostatin analogues and diazoxide are not effective in the treatment of NICTH.