SUN-319 Failure Of Pasireotide To Control Hypoglycemia In A Men-1 Patient With Metastatic Insulinoma

Abstract

Background: Pasireotide appears to be a promising therapeutic approach to refractory hyperinsulinemic hypoglycemia, since hyperglycemia is a frequent side effect when used in the treatment of other neuroendocrine diseases. Clinical case: A 39-year-old woman with MEN1 and severe hypoglycemic episodes was diagnosed with a 5x4 cm lesion in the pancreatic tail in 1999 compatible with insulinoma. The tumor was successfully removed and pathology report described an encapsulated lesion with free margins and low mitotic index. After surgery she became asymptomatic and was regularly followed-up. She started to gradually gain weight from 2004 to 2015, achieving a BMI of 41 kg/m² and decided to undergo a bariatric surgery at another center in 2016. She underwent a gastric bypass and her liver was randomly biopsied. Surprisingly, biopsy revealed a grade I NET. Hypoglycemic symptoms recurred, but she didn't report them immediately, attributing it to the bariatric procedure. An abdominal CT was then performed and showed multiple contrast-enhancing lesions in the pancreatic head, body and tail ranging 0.5-0.8 cm in size, as well as randomly distributed hepatic lesions. A selective arterial calcium stimulation test was performed and identified that both the pancreatic and hepatic lesions were functioning. Short-acting octreotide was prescribed, with worsening of hypoglycemic episodes. Diazoxide was poorly effective and had multiple side effects. Other therapies were considered but due to their toxicity profile, we opted to test pasireotide. After informed consent, a flash glucose monitoring sensor (FreeStyle Libre) was implanted 4 days before starting the drug. In this pretreatment period, her mean glucose was 83 mg/dl. Pasireotide 0.6 mg twice daily was started and she wore the sensor for 10 days. While on treatment her mean glucose was 85 mg/dl. The average 14-day glucose level (including both pretreatment and treatment periods) was 84 mg/dl, the percent of time between 70-140 mg/dl (target range) was 41%, above target 11% and below target 48%. The number of hypoglycemic events was 69 with an average duration of 143 minutes. Although mean glucose levels did not differ during treatment, the patient agreed to undergo another course of treatment, and a new sensor was implanted. In this phase, the patient became progressively symptomatic. This full 14-day treatment period presented an average glucose of 66 mg/dl, the percent of time in range was 28%, above target 6% and below target 66%. The number of hypoglycemic events was 75 with an average duration of 182 minutes. She discontinued the drug after noticing more frequent and severe crises. Conclusion: In contrast to scarce published evidence favoring treatment success, this is the first report of failure to control hypoglycemia in metastatic insulinoma with pasireotide, suggesting that different tumor characteristics may be responsible for adequate response.