(12.11) Recurrent Hypoglycemia Secondary to Metastatic-IGF-2-secreting Anaplastic Hemangiopericytoma

Anaplastic hemangiopericytoma (AHP) is a rare malignant mesenchymal tumor that arises from pericytes. Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic process that has been associated with AHP and is driven by increased production of insulin-like growth factor 2 (IGF2). We present the case of a patient with metastatic AHP who presented with recurrent hypoglycemia due to NICTH.

Case(s) Description :

A 51-year-old man with a history of AHP of the brain with metastasis to the lungs, liver and right kidney presented with loss of consciousness at home. He had a fingerstick glucose of 20mg/dL which improved to 160mg/dL with recovery of his mental status after dextrose administration. During his hospitalization, a 72-hour fast was done which terminated after 28 hours with a plasma glucose of 50mg/dL, pro-insulin 1.1pmol/L (3.6-22pmol/L), c-peptide 0.10ng/mL (0.5-2.0 ng/mL), beta-hydroxybutyrate 0.22mmol/L (< 0.28mmol/L), insulin antibodies 0.00nmol/L (0.00-0.02nmol/L), cortisol 10.52ug/dL (10-20ug/dL), IGF-1 40ng/mL (37-245ng/mL), and IGF-2 2539 ng/mL (333-967 ng/mL). He was given 1mg IV glucagon at the end of the fast which revealed a glucose rise above 25mg/dL. Overall, these tests supported a diagnosis of a non-islet cell mediated process. Given the unresectable metastatic burden of disease, he was started on glucocorticoids up to 25mg daily with improvement in glucose levels. He was discharged with close follow up with his outside oncologist.

Discussion :

The lab abnormalities in our patient were consistent with NICTH. Excess IGF-2 can cause hypoglycemia by several mechanisms including stimulation of insulin receptors which increases glucose uptake by peripheral tissue, inhibition of lipolysis, and suppression of gluconeogenesis/glycogenolysis as well as counter-regulatory hormones like glucagon and growth hormone. There is no standard management for recurrent hypoglycemia in patients with AHP when disease is unresectable. Medical interventions that may provide glycemic support include dextrose infusions, glucocorticoids, growth hormone and/or glucagon. Yet, none of these therapies are well-studied and are based on case reports. Targeted treatments that can be used long-term still need to be studied. This case highlights the importance of recognizing NICTH as a paraneoplastic syndrome, the extensive diagnostic testing involved, and the limited knowledge on treatment options.