Recurrent IGF-2 Mediated Hypoglycemia Associated with Solitary Fibrous Tumor

Presentation Number: MON 606
Date of Presentation: April 3rd, 2017

Sarah Fishman*1, Andrew Moses2, Shawanda Patterson1 and Edward Merker1
1Northwell Health, Lenox Hill Hospital, New York, NY, 2Northwell Health, Lenox Hill Hospital, new York, NY

Abstract

Background: Paraneoplastic hypoglycemia is a rare presentation of malignancy, and may be mediated by tumor secretion of insulin, replacement of liver and adrenal tissues, or by non-islet cell tumor secretion of other intestinal hormones involved in glucose metabolism.

Clinical Case: A 61 year old male presented to the hospital with altered mental status and slurred speech. His temperature, heart rate, blood pressure, respiratory rate and oxygen saturation were all within normal limits. Bloodwork revealed normal electrolytes, creatinine, BUN, glucose, liver enzymes, TSH, white and red blood cell counts. Urinalysis was negative for protein, ketones, glucose and infectious markers. Both a CT and MRI of the head were negative for acute pathology. Chest Xray revealed a large left sided thoracic mass, and CT of the chest was notable for a 21 x 16.5 x 16.7 cm heterogeneous mass with areas of necrosis. His mental status improved with administration of IV fluids, but his hospital course was complicated by recurrent pneumonia, episodes of symptomatic hypoglycemia, and failure to thrive. Biopsy of the mass revealed a solitary fibrous tumor and resection of the mass was planned. On pre-operative evaluation for continued hypoglycemic episodes, he was found to have glucose levels ranging from 40-237 mg/dl (70-99), HbA1C 5.1% (4.8-5.6), undetectable insulin levels (3-17mU/ml), C-peptide <0.4ng/ml (0.9-7.1), ACTH 11pg/ml (0-46), morning cortisol 15 ug/dl (3.9-37.5), IGF-1 45 ng/ml (49-188), IGF-2 960ng/ml (333-967), IGF binding protein-3 1.5mg/ml (3.2-6.6), GH <0.1 ng/ml (<5). Based on these findings, we attributed his recurrent hypoglycemia to an IGF-2 producing tumor. Following resection, the diagnosis of solitary fibrous tumor was confirmed, and the patient experienced no further hypoglycemic episodes.

Conclusion: Solitary fibrous tumor is a rare mesenchymal tumor belonging to a group of non-islet cell tumors that lead to hypoinsulinemic hypoglycemia via dysregulated IGF-2 production. Loss of genetic imprinting leads to increased production of IGF-2 and alternate larger isoforms of IGF-2 that are unable to form a ternary complex with acid labile subunit and IGF-binding protein-3. IGF-2 in excess can stimulate insulin and IGF-1 receptors in many tissues leading to hypoglycemia without ketosis. These tumors have been reported in nearly all solid organs and soft tissues, including CNS, deep tissues of the extremities, and bone. Typical symptoms of hypoglycemia are often absent due to the gradual onset and variable frequency of hypoglycemic episodes. Altered mental status and lethargy due to paraneoplastic hypoglycemia may be mistaken for side effects of narcotic and sedatives in patients with large tumor burden. Treatment with corticosteroids and recombinant growth hormone are effective treatments for hypoglycemia, but resection of the tumor is required for definitive treatment.

 

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