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.
<Insert Figures 1A and 1B>
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.
<Insert Figures 2 and 3>
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.
<Insert Figure 4>
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.