Hypoglycemia associated with insulin like growth factor 2 (IGF-2) producing tumors typically occurs in the fasting state and is a clinically significant, often unrecognized syndrome, associated with certain neoplasms.
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A 38-year-old Hispanic male with history of alcohol abuse and hepatocellular carcinoma presented with one month of worsening abdominal pain. CT multiphase demonstrated significant hepatomegaly and multiple metastases. During the course of admission, patient had very poor oral intake due to abdominal pain and early satiety caused by gastric compression from his enlarged liver. He became altered, and there was concern for brain metastases, ischemic stroke, or over sedation from narcotics. Serum glucose level was 38 mg/dl (normal range) and a dextrose containing fluid was administered with improvement in cognition. Serum insulin level while hypoglycemic was 1.7 mIU/L (low range), C-peptide was 0.4 ng/mL (normal range), beta-hydroxybutarate was 1.0 mmol/L (normal range). No biochemical evidence of cortisol deficiency or hypothyroidism was observed. In addition, no increase in glucose values occured following glucagon stimulation. Serum IGF-2 was elevated to 531, consistent with the etiology of his hypoglycemia. He continued to have poor oral intake with multiple fasting hypoglycemic episodes initially making it difficult to wean off dextrose containing fluids. Prednisone 40 mg daily was started, hypoglycemic episodes stopped and dextrose fluids were eventually discontinued.
IGF-2 mediated hypoglycemia has been observed in patients with mesenchymal or epithelial origin tumors with hepatocellular carcinoma being the most common, accounting for 20% of overall cases. In the fasting state, IGF-2 activates insulin-related receptors, and inhibits gluconeogenesis, glycogenolysis, ketogenesis as well as growth hormone and glucagon release. The suppression of these compensatory hormones and biochemical processes leads to an increased propensity for fasting hypoglycemia. The mainstay of treatment involves surgical resection of the tumor, which was not possible in this case given the extent of his disease. Glucocorticoids are one of the most effective medical therapies to prevent hypoglycemia in these patients, as seen in this case. Recombinant GH has also been shown to reduce hypoglycemia in these patients. Clinicians should be aware of this syndrome and it should be considered in any cancer patient presenting with altered mental status or change in behavior.
Internal Medicine and Pediatrics Resident Physician
University of Southern California
Los Angeles, California
Erica Patel is a second year Internal Medicine and Pediatrics resident at the University of Southern California. She attended the University of Southern California Keck School of Medicine, graduating in 2017, as well as the University of Southern California for her undergraduates degrees in Narrative Medicine and Biological Sciences. She is interested in international medicine and has done work in Honduras, Mexico, and Kenya thus far. Erica has a particular interest in transitional Endocrinology.
Director Thyroid Clinic, Program Director of Endocrinology Fellowship Program
LAC+USC Medical Center
A native of Los Angeles, Dr. LoPresti received both his medical degree and his Ph.D. in physiology from the University of Southern California.
He first joined the Trojan family in 1974 as a biology undergraduate and finished his residency at the LAC+USC Medical Center ten years later. Dr. LoPresti has contributed to over fifty presentations, recently lecturing on a case of an aggressive Papillary Thyroid Cancer arising in the third trimester of pregnancy. In addition, he has had leadership roles in the American Thyroid Association and has been published in numerous journals, abstracts and book chapters. He serves as the program director of the endocrinology fellowship program and is the director of the thyroid clinic.