Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report.
BACKGROUND
Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it.


METHODS
A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm x 25 cm x 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT.


CONCLUSIONS
Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11-20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established.
Escobar
Guillermo A
GA
Department of Surgery, Division of GI, Tumor and Endocrine Surgery, University of Colorado Health Sciences Center, 4200 E, 9th Ave, Denver, CO 80262, USA. guillermo.escobar@uchsc.edu
Robinson
William A
WA
Nydam
Trevor L
TL
Heiple
Drew C
DC
Weiss
Glen J
GJ
Buckley
Linda
L
Gonzalez
Rene
R
McCarter
Martin D
MD
D000328:Adult; D005091:Exons / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis / Q000628:therapy; D007421:Intestine, Small / Q000473:pathology / Q000601:surgery; D007813:Laparotomy / Q000379:methods; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D010257:Paraneoplastic Syndromes / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D019009:Proto-Oncogene Proteins c-kit; D005947:Glucose