Hypoglycemia in a patient with a “big"-IGF-II producing tumor

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 326-337-Hormone-Dependent Tumors
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-335
Gonnie M. Alkemade*1, Martijn Bakker1, Bart Rikhof1, Frank F.A. IJpma1, Philip M. Kluin1, Jaap van Doorn2 and Robin P.F. Dullaart1
1University Medical Center Groningen, Groningen, Netherlands, 2University Medical Center Utrecht, Utrecht, Netherlands
Background:  Non-islet cell tumor-induced hypoglycemia is a rare condition that should be considered in the differential diagnosis of symptomatic hypoglycemia. Aberrant processing of IGF-II within the tumor, resulting in elevated “big” plasma IGF-II levels, has been recently proposed to be causally implicated in hypoglycemia. Here we describe a patient who presented with hypoglycemia due to a “big”-IGF-II producing tumor, with full recovery of the initially suppressed plasma insulin and IGF-I levels and disappearance of symptoms after surgical removal of the tumor.

Clinical Case: A 60 year old, previously healthy man was initially seen by an urologist for lower urinary tract symptoms. While performing rectal examination, the urologist incidentally leaned on the patient’s abdomen, thereby discovering a large abdominal mass. A CT-scan revealed an oval lesion of 12 x 16 x 16 cm, dorsal of the bladder, just reaching the aorta bifurcation. There were no signs of enlarged lymph nodes or metastasis. Shortly thereafter he presented with symptomatic neuroglycopenia with a blood glucose level of 1.9 mmol/L. After glucose i.v. and glucagon i.m. blood glucose levels normalized and the patient recovered. A fasting test showed symptomatic hypoglycemia with a plasma glucose level of 2.3 mmol/L already after 4 hrs of fasting. Both plasma insulin (0.2 mU/L) and C-peptide levels (<10 pmol/L) were suppressed, excluding endogenous hyperinsulinemia. Plasma IGF-I was also fully suppressed (<2.6 nmol/L). The plasma total IGF-II level was normal (460 ng/mL; +0.57 SD-score), but the pro-IGF-IIE (“big”-IGF-II) level was markedly raised (98 ng/ml; +8.97 SD-score). The tumor, which was located in the abdominal cavity and retroperitoneum, was removed completely during surgery. Histopathological examination revealed a large solitary fibrous tumor weighing 1.76 kg, without unfavorable features of necrosis or high mitotic activity. The patient fully recovered, and passed a 72h fasting test without developing hypoglycemia (plasma glucose 4.6 mmol/L). Plasma “big”-IGF-II levels had normalized (11.9 ng/mL; -1.11 SD), coinciding with normalization of plasma insulin (5.1 mU/L), C-peptide (632 pmol/L) and IGF-I (13.0 pmol/L; -0.92 SD-score). He is still asymptomatic one year after surgery. Based on limited literature data 10-years recurrence-free survival is expected to be approximately 50%.

Conclusion: “Big”-IGF-II producing tumors may cause symptomatic hypoglycemia, and should be considered in tumor patients presenting with hypoglycemia. In such cases, the “big”IGF-II is thought to disrupt the ternary complex of IGF-II, IGF-binding protein 3 and acid labile subunit, thereby increasing circulating free IGF-II, which in turn activates the insulin receptor and suppresses the pituitary GH-IGF-1 axis. The present case further demonstrates that the ensuing plasma IGF-I suppression is fully reversible.

Nothing to Disclose: GMA, MB, BR, FFAI, PMK, JV, RPFD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm