8207 Insights From a Case of Insulinoma and Possible Genetic Variants in a Young Woman With Recurrent Hypoglycemia
Authors: Brandao M A , Bharara A , Moncada Castro V I , Tsai T C , Wu Y C , Marquez Flores S , Divari K 
Published: October 2024

Disclosure: M.A. Brandao: None. A. Bharara: None. V.I. Moncada Castro: None. T.C. Tsai: None. Y. Wu: None. S. Marquez Flores: None. K. Divari: None.

Introduction: Insulinomas are neuroendocrine neoplasms causing hyperinsulinemic hypoglycemia. They are rare, with a prevalence of 1-4 people per million of the general population. Key features are symptoms of hypoglycemia, low plasma glucose, and symptom relief by correcting hypoglycemia. Here, we report a patient with recurrent hypoglycemia who was found to have insulinoma. Several variants of uncertain significance (VUS) were detected in this patient. This gives us some insights into a broader perspective. Clinical case: A 28-year-old healthy female was found unresponsive by her partner. Blood glucose (BG) was 40 mg/dL when paramedics arrived. She received dextrose and rapidly recovered. She was briefly hospitalized and received glucose infusion with improvement. Subsequently, the patient developed episodes of blurry vision and weakness. She had been eating more frequently to prevent symptoms. Her weight was stable at 65.77 kg. She had not been on any medications. She continued to experience hypoglycemic episodes with BG dropping to 30 mg/dL, so she sought evaluation from an endocrinologist. Laboratory work-up showed Proinsulin of 530.6 pmol/L, C-peptide 5 ng/ml, TSH 1.01 mciu/ml, Beta-hydroxybutyrate (BHOB) 0.7 mg/dL, hemoglobin A1c 4.7%, calcium 8.9 mg/dL, albumin 4.1. Abdominal computed tomography (CT) scan showed an 11 mm nodule anterior to the pancreatic tail. No discrete calcification was noted. Magnetic resonance imaging (MRI) of the abdomen redemonstrated the 10 x 6mm, slightly exophytic lesion in the pancreatic tail. Therefore, she underwent laparoscopic enucleation with pathology showing a 1.7cm well-differentiated grade 2 neuroendocrine tumor, with positive margins. Given its indolent nature, further surgical resection was not recommended. Germline testing showed several VUS: the AXIN2 gene (c.1822C&gt;G), GPC3 gene (c.565G&gt;T), NF2 gene (c.296A&gt;G), RECQL4 gene (c.2791C&gt;G). However, no pathogenic variants were identified. Surveillance MRI of the abdomen six months after the surgery has shown no evidence of recurrent disease. The patient has remained euglycemic and symptoms have not recurred. Conclusion: Insulinomas are typically sporadic but may occur due to an activating T372R mutation in the Yin Yang. It may also occur in the setting of multiple endocrine neoplasia type 1 (MEN-1) syndrome caused by MEN1 gene mutations. Although no pathogenic variant mutations associated with insulinoma were found, several VUS that have not yet been described as related to insulinoma were detected in this patient. Routine genetic testing in newly diagnosed patients is not always recommended. Therefore, further efforts are required to understand genetic mutations and epigenetic modifiers associated with insulinoma. Validation of identified VUS and additional genetic testing in young patients with insulinoma are crucial.

Presentation: 6/2/2024