(10.14) When the Apple Falls Far From The Tree: Sporadic Insulinoma in 30 Year Old Female with Second Degree Relatives with Novel MEN-1 Mutation.

Sporadic insulinomas average 3:2 more often in women than men in the 3^rd-6^th decade of life. Multiple endocrine neoplasia 1 (MEN-1) associated insulinomas tend to happen a decade earlier than sporadic. We discuss a patient with family history of novel MEN-1 gene mutation in 2nd degree relatives presenting with confusion, slurred speech, hypoglycemia and an insulinoma.

Case(s) Description :

30 y.o. female history of PCOS, melanoma, atypical migraines presenting with worsening episodes of blurred vision. Visual symptoms started one year ago with associated “pins and needles” sensation and no headaches. Symptoms were exacerbated by skipping meals, while incompletely improved by eating. Symptoms progressively worsened over 2 months leading up to presentation when she had an episode of blurry vision, sense of impending doom and speech difficulty witnessed by family. Patient was 1st evaluated at an outside facility and noted for low blood glucose of 53 mg/dL. CT of abdomen pelvis revealed a 1.7 x 2.1 cm pancreatic head lesion. Hyperparathyroidism workup was benign, with normal calcium and iPTH levels. MRI of pituitary normal. The patient was transferred to our institution for further evaluation.

Family history notable for novel MEN-1 gene mutations in both paternal aunt and uncle, maternal history was not available. 72 hour fast reached a conclusive diagnosis after 6 hours, with symptomatic hypoglycemia of 48 mg/dL on fingerstick and 50 mg/dL on serum sample, along with a C-peptide 1.89, insulin 8.2, beta hydroxybutyrate less than 0.2. IGF-2 916, IGF-I 228 with a ratio of 4:1. Sulfonylurea screen and insulin antibody negative. Patient was discharged with glucometer and diazoxide. One month later she had successful enucleation of the pancreatic head and became euglycemic without insulin. Subsequent genetic testing and wasn’t positive for MEN-1 gene, but was positive for MutS homolog 6 (MSH-6) and will require further cancer screening.

Discussion :

More than 1300 mutations on the MEN-1 gene have been known to cause Multiple Endocrine Neoplasia type 1, and include substitution, non-sense, frameshift and splice site mutations. These mutations can cause neoplasia of the parathyroid, the anterior pituitary and the neuroendocrine tissue of gastro-entero-pancreatic organs. Patients with history of any of these diseases in 1st degree relatives should be offered screening. Our case reveals paternal family history of parathyroid neoplasia in both aunt and uncle, with novel MEN-1 gene mutation confirmed in 2010. Patient’s father was not a carrier of mutation. The family pedigree cannot be fully evaluated due to early passing of patient’s grandfather. Patient was genetically evaluated and did not carry a mutation for MEN-1 gene, but was positive for MSH-6. Reviewing patient’s personal medical history revealed history of melanoma at young age. There is limited literature currently demonstrating links between MSH-6 gene, melanoma and insulinoma incidence. Though this may be coincidental regardless of the rest of family history, this case of sporadic insulinoma raises thoughts of further research into other loci that may be oncogenic as we further advance gene technology.