Abstract
Non islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome generally seen in tumors of mesenchymal and hepatic origin. This syndrome is characterized by life threatening hypoglycemia caused by over expression of high molecular weight insulin-like growth factor 2 (IGF 2). The main stay of treatment is surgical resection of the tumor with no clear medical management being reported as standard of care.
We present the case of a 72 year old Cambodian man with no history of diabetes mellitus who presented to our institution with severe hypoglycemia complicated by a seizure and was found to have hepatocellular carcinoma (HCC). Hypoglycemia occurred during times of fasting. Laboratory evaluation revealed a serum glucose of 30mg/dl with insulin level of 2.2 mcIU/mL [2.6 - 24.9 mcIU/ml], C-Peptide of 0.17 ng/mL [0.80 - 3.85 ng/ml], BHB <0.1 mmol/L [0.0 - 0.3 mmol/L] and Proinsulin of <0.4 pmol/L [< or = 18.8 pmol/L]. Hypoglycemic agents screening was negative. Insulin Antibody was negative <0.4 U/mL [<0.4 U/mL] and adrenal insufficiency and hypothyroidism was ruled out. Patient was found to have an elevated IGF 2: IGF 1 ratio of 78 confirming the diagnosis of NICTH. IGF 2 level was 780 ng/ml [333 - 967 ng/ml] while IGF-1 was < 10 ng/ml [32-200 ng/ml] He was not a candidate for surgery due to portal vein involvement and tumor radioembolization was unsuccessful. Despite Prednisone dose of 10 mg twice daily and frequent complex carbohydrate meals, he still continued to have hypoglycemia ultimately requiring hospitalization. During hospitalization, he was treated with 50% dextrose infusion, 37.5 grams of dextrose gel every three hours and frequent small meals. Hypoglycemia remained refractory and a trial of diazoxide was ineffective. He was then started on octreotide with titration to 100mg every 8 hours with significant reduction in hypoglycemic episodes. He continues to remain on octreotide, Prednisolone 20mg twice a day, dextrose gel and dextrose infusion. Goal is to wean dextrose infusion and transition him to Pasireotide 40mg monthly.
Hepatocellular carcinoma has been associated with NICTH in the literature. NICTH is characterized by an IGF2:IGF1 ratio >10 as there is no commercially available assay for big IGF II. Definitive treatment involves surgical resection or tumor debulking. Octreotide has antiangiogenic and antineoplastic properties and unfortunately, few studies have shown improved survival and quality of life in patients with advanced HCC. In the case of our patient, tumor was unresectable and NICTH improved with octreotide and prednisolone.
Non-islet-cell tumor hypoglycemia as first manifestation of an advanced hepatocellular carcinoma
