Case Presentation
Our case involves a 73-year-old woman with a prior medical history of Diabetes Mellitus type 2 and a recent diagnosis of non-hormone-secreting high-grade pancreatic neuroendocrine tumor with metastases to the liver, who presented for admission for bilateral pulmonary embolism. Pancreatic neuroendocrine tumor had been diagnosed from liver biopsy specimens showing positivity for Synaptophysin and Chromogranin. The pathology images are shown in Figure 1A and 1B.
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The patient’s only complaints were generalized weakness, and she denied any respiratory complaints upon presentation. The patient was previously diabetic as well and was on a home regimen of Tresiba insulin 20 units daily and Metformin 1000mg twice daily. She had taken both medications the day before the presentation, and neither was restarted on admission as the patient’s blood glucose was near normal. Physical examination findings were unremarkable, including a normal oxygen saturation on room air. Laboratory findings revealed significant hypoglycemia with a blood glucose of 48. The patient was started on IV Dextrose 5% with normal saline at 125ml/hr and IV heparin infusion at 18 units/kg/hr and was subsequently admitted for further management. Of note, the patient’s pancreatic tumor prior to presentation was 2.7cm in size and was a Grade 3 tumor with a Ki-67 proliferative index of 40%. Figures 2 and 3 demonstrate the initial pancreatic mass with liver metastases on imaging. She was stage IV at this point in time based on the scoring of T2, N1, M1a using the WHO guidelines.
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The patient continued to have persistent hypoglycemia over the next few days and was subsequently started on dextrose 10% with free water at 80 ml/hr. The patient’s appetite was also poor, contributing to her hypoglycemia episodes. On hospital day 4, the patient had a syncopal episode due to a blood glucose level of 30. This improved with the administration of two dextrose 50 ampoules. Endocrinology workup was initiated, and the patient was started on a 72-hour fasting test. Plasma glucose was 130mg/dL at the start of the test (normal is >70mg/dL). The patient made it to only 2 hours of fasting before becoming symptomatic. Blood glucose reached 53 mg/dL at that time, and the decision was made to discontinue the test. Blood work done at that time revealed elevated c-peptide levels of 7.0 ng/ml (normal range is 1.1 to 4.4 ng/ml) and an insulin level of 136 µU/ml (normal range is 2 to 25 µU/ml). The patient was confirmed to have had a conversion of her high-grade neuroendocrine tumor from non-hormone-secreting to an insulinoma. On hospital day 5, the patient was started on an octreotide injection of 100 mg thrice daily by the consulting endocrinologist. She was also started on Dexamethasone 2mg twice daily. Despite these interventions, the patient continued to have frequent episodes of hypoglycemia. Her oral caloric intake had improved during this time and did not significantly contribute to hypoglycemia. At this point, the first line treatment for insulin-related hypoglycemia, Diazoxide, was considered by the treatment team. On hospital day 7, the patient was started on diazoxide 50mg every 8 hours. Her blood sugar continued to fluctuate after this treatment, and she remained on a Dextrose 10% infusion. Her Dexamethasone was switched to oral prednisone 40 mg daily. On this regimen, the patient’s blood glucose levels did improve. She was weaned from Dextrose 10% infusion with further episodes of significant hypoglycemia. She was discharged home on hospital day 10 with a regimen of prednisone 40 mg daily and diazoxide 75 mg at night. The patient was also started on FOLFOX chemotherapy prior to discharge. The entire timeline of our case is shown in Figure 4.
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The patient did establish outpatient follow-up with oncology and endocrinology. The patient was hospitalized multiple times for recurrent hypoglycemia. After these episodes, she was also maintained on Octreotide as an outpatient. Alternative treatment options such as Everolimus and Sunitinib were discussed with the patient and family, including their risks and benefits. The patient and family declined these interventions. On repeat staging imaging, the patient was noted to have a spinal lesion at T12. This was biopsied and positive for synaptophysin and chromogranin, confirming the further spread of the neuroendocrine tumor. Ki-67 proliferative index was greater than 50%, indicating a grade 3 tumor as well.
The patient continued to do poorly overall. She declined palliative chemotherapy and was eventually placed in hospice care. The patient was discharged home and passed away a few weeks later.