Endocrine Abstracts

Non-islet cell tumor hypoglycemia (NICTH) is a rare phenomenon that is likely mediated by insulin growth factor 2 (IGF-2). IGF-2 excess results from tumor overproduction of either mature IGF-2 or incompletely processed IGF-2 (“big IGF-2”), which binds to the insulin receptor causing hypoglycemia. We present a case of IGF-2 mediated hypoglycemia secondary to adrenocortical carcinoma, as well as a series of 8 previously published cases. An 83-year-old male with a history of prostate cancer and arrythmia presented to the emergency department for confusion, weight loss, and abdominal distension. Blood glucose was 1.3 mmol/l (3.3-11.0 mmol/l), and treatment with dextrose lead to improved mentation. Imaging showed a 17cm L adrenal mass, and adrenal workup showed non-suppressed cortisol after 1 mg dexamethasone suppression test (DST), elevated DHEAS and elevated estradiol. IGF-1 was low-normal, and IGF-2 was normal. Ratio of IGF-2: IGF-1 was 10.8, which is diagnostic of IGF-2 mediated hypoglycemia. A combination of dexamethasone and uncooked corn starch was effective in managing hypoglycemia, allowing for discontinuation of IV dextrose. We identified 8 additional cases of IGF-2 mediated hypoglycemia secondary to ACC. The median age at diagnosis was 41. Most (n = 5) cases had stage IV disease at presentation. The median glucose for the critical sample was 1.8 mmol/l. All insulin and C-peptide levels were either normal or suppressed. Serum IGF-1 was suppressed in 89%, and IGF-2 was elevated in 42%. Every case had an IGF-2: IGF-1 ratio of >10, with a median ratio of 27.8 (range 10.8-84). Death was reported in most (n = 6) cases; median time between diagnosis and death was 17.5 (range 3 - 48) months. Medical management for hypoglycemia involved glucose administration, corticosteroids, octreotide, diazoxide, recombinant growth hormone, and everolimus with varying efficacy. IGF-2 mediated hypoglycemia in the setting of ACC is generally associated with advanced disease and poor prognosis.