(CSEMP042) IGF-2 MEDIATED HYPOGYLCEMIA IN A PATIENT WITH SUSPECTED ADRENOCORTICAL CARCINOMA

Abstract: Background
Insulin growth factor-2 (IGF-2) mediated hypoglycemia is a rare paraneoplastic syndrome caused by tumoral overproduction of IGF-2 or abnormally processed IGF-2 (“big IGF-2”), which binds to the insulin receptor (IR). IGF-2 mediated hypoglycemia secondary to adrenal cortical carcinoma (ACC) is exceedingly rare, with less than 10 reported cases.

Case Presentation
An 83-year-old man presented to the emergency department for confusion and a blood glucose level of 1.3mmol/L (3.3-11.0 mmol/L). History was significant for weight loss, early satiety, and abdominal distension over the past 3 months. No Cushingoid features were observed. Serum potassium was 2.7mmol/L (3.5-5.0mmol/L) and critical sample (drawn with serum glucose of 3.5mmol/L) showed insulin < 6pmol/L ( < 120pmol/L), C-peptide 0.04nmol/L (0.4-1.40nmol/L), and beta hydroxybutyrate (BOH) 0mmol/L. Serum cortisol was 188nmol/L (170-500nmol/L) following a 1mg dexamethasone suppression test, with an adrenocorticotropic hormone (ACTH) of 2.5pmol/L (2.0-11.5pmol/L). Dehydroepiandrosterone sulfate (DHEAS) was 75.5umol/L (0.4-3.3umol/L) and estradiol was 241pmol/L ( < 160pmol/L). Aldosterone-to-renin ratio and 24-hour urine metanephrines and normetanephrines were normal. Insulin growth factor-1 (IGF-1) was 57ug/L (15-245ug/L), and IGF-2 was 615ug/L (333-967ug/L). IGF-2: IGF-1 ratio of 10.8 ( < 3). CT scan of the abdomen demonstrated a 14.4 x 12.1 x 17.7cm mass in the left suprarenal fossa. FDG PET was intensely hypermetabolic, suggestive of ACC without evidence of other primary malignancy or metastatic disease. The patient was not a candidate for surgery due to tumor invasiveness. Hypoglycemia was refractory to diazoxide and prednisone 60mg daily. Uncooked cornstarch and dexamethasone 4mg twice daily were implemented and successful at preventing severe hypoglycemia. He was referred to radiation oncology and medical oncology for consideration of palliative therapies.

Conclusion
We present a very rare case of IGF-2 induced hypoglycemia secondary to ACC. Hypokalemia, suppressed insulin, and undetectable BOH are in keeping with activation of insulin receptors by IGF-2. Interestingly, IGF-2 levels are typically normal, as the structure of big IGF-2 leads to increased bioavailability and binding to IR. IGF-1 is low or low-normal due to negative feedback of IGF-2. Management in this case was focused on preventing hypoglycemia. Glucocorticoids are usually first line of treatment as they stimulate gluconeogenesis and decrease production of big IGF-2 (1). We postulate that dexamethasone was more effective than prednisone due to its longer half-life. Cornstarch is a complex carbohydrate that is digested slowly which helps prevent fasting hypoglycemia. Diazoxide was ineffective because it works by inhibiting pancreatic insulin release and has no effect on IGF-2.