He was admitted for a 72 hr starvation test. Thyroid, cortisol, renal and liver parameters were normal. He was started on 72 hr fast at 12 noon with only water allowed, under supervision with hourly RBS, hemodynamics and urine ketone monitoring. Blood glucose levels at start of test were 90mg%, urine sugars and ketones negative. Hourly glucose monitoring on glucometer showed a declining trend and within 5 hrs he developed symptoms of sweating, palpitations and restlessness. Blood glucose levels dropped to 35mg% hemoglucostix, corroborated with a lab reading of 29mg% with urine sugars and ketones negative. Blood samples were collected and test was terminated after administering N glucose. Insulin levels at time of hypoglycemia was 35µU/L, C-peptide 3.5ng/ml cortisol 30mcg/dl and insulin antibodies negative. This proved as a case of endogenous hyperinsulinemic hypoglycemia. He then underwent a Triphasic CT abdomen, which showed a lesion in the neck of the pancreas approx 2.5 x 2 cm, enhancing on contrast, suggestive of insulinoma. Workup for MEN syndromes was negative. Meanwhile, he was maintained on a 2 hourly complex carbohydrate meal plan in the hospital with N steroids to maintain his blood glucose levels.
He then underwent a central pancreatectomy to remove the tumor. Blood glucose levels normalized within minutes of tumor excision and were consistently maintained without N dextrose between 80-140 mg% till discharge. All his symptoms resolved and he was able to sleep through the night. He was discharged a week later with no symptoms or documentation of hypoglycemia. On follow up in OPD after a month he remained euglycemic, comfortable, sleeping well, no repeat episodes and lost 3 kg weight.
This case illustrates a case of a pancreatic neuroendocrine tumor producing insulin, viz insulinoma.
Insulinomas are rare insulin secreting pancreatic neuroendocrine tumors, occurring in 3-10 cases per million people per year. They are mostly sporadic and benign but can rarely be malignant or a part of MEN syndromes. They are commonly located in the head and neck, rarely in the tail.
Insulinomas present with typical repeated episodes of hypoglycemia, commonly occurring in early morning hours, within a few hrs of fasting. A diagnosis of hypoglycemia is made if Whipple’s triad viz: symptoms of hypoglycemia, RBS at time of hypoglycemia of<45mg% and relief of symptoms with glucose. A normal thyroid, cortisol, liver and renal parameter needs to be documented, before proceeding further. Once this is established, the next step is to document endogenous hyperinsulinemia with an extended 72 hr fast with blood samples for S. Insulin, Cpeptide and insulin antibodies collected at time of hypoglycemia. S. Insulin levels >6µU/ml, Cpeptide > 2.5ng/ml with an RBS <45mg% and negative screen for sulfonylurea. establishes endogenous hyperinsulinemic hypoglycemia. The next step is to localize the tumor. A triphasic MDCT scan of abdomen with contrast is the preferred imaging modality and these tumors enhance well on contrast. However, insulinomas are usually small lesions (<lcm) and difficult to detect. Other imaging modalities like endoscopic ultrasound, PET CT or dotatate scan and the invasive arterial stimulation with venous sampling (ASVS) with intraop ultrasonography of the pancreas help to localize when lesions are small or not detected on CT
Surgical excision of the tumor is curative in majority of cases. Traditional operations for pancreatic resection are Whipple’s procedure or partial pancreatectomy which can lead to loss of substantial part of pancreas leading to diabetes and exocrine pancreatic insufficiency. Enucleation is possible in some cases. Symptoms of hypoglycemia usually resolve within a few hours of resection and long term remission rates are> 95%. When the tumor is difficult to localize, medical management with diazoxide, octreotide, steroids orverapamil can be tried.
Our patient was a classical case of hyperinsulinemic hypoglycemia presenting with severe neuroglycopenic symptoms for almost 4 yrs before the tumor could be localized. Given the small size of tumor, he underwent a central pancreatectomy, excising only the part of pancreas where the tumor was located and was cured of hypoglycemia. This pancreas preserving procedure prevented the development of diabetes and exocrine insufficiency.