Persistent hypoglycemia despite oral therapy
An 82-year-old woman was brought to the ED after a fall. Her medical history was significant for hypertension, recurrent urinary tract infections, atrial fibrillation and recently diagnosed dementia.
Her medication list included Pradaxa (dabigatran, Boehringer Ingelheim), Aricept (donepezil, Pfizer), atenolol, lisinopril, and calcium and vitamin D supplements.
She was found to be combative and disoriented. Her capillary blood glucose level was 31 mg/dL, and after the IV administration of dextrose, her mental status returned to baseline. She was admitted to the hospital for further evaluation.
Laboratory testing, imaging
Her family reported an 8-month history of forgetfulness and a 3-month history of recurrent falls. After hospital admission, she was found to have bradycardia and persistent hypoglycemia despite a continuous infusion of fluids with 5% glucose. Atenolol was discontinued because of the potential to block glucagon secretion. Hypoglycemia was attributed to low oral intake; however, her symptoms persisted in the hospital despite adequate food consumption. Her husband reported that the patient had no personal or family history of diabetes and that no insulin or oral hypoglycemic agents were kept at home.
On initial laboratory testing, a random blood glucose measurement was 46 mg/dL, insulin level 20.3 mIU/L and C-peptide 3.7 ng/mL. Serum sulfonylurea panel was negative. Morning cortisol level was 12 µg/dL, and after a cosyntropin adrenal stimulation test, the patient showed a normal adrenal response with a cortisol of 26 µg/dL at 30 minutes and 30 µg/dL at 60 minutes. Her thyroid-stimulating hormone level was normal at 1.5 mIU/L. The remainder of a routine complete blood count and chemistry panel were unremarkable.
Abdominal CT (Figure) showed an 8-mm arterially enhancing lesion within the body of the pancreas near the junction with the tail, which was concerning for neuroendocrine tumor.
The patient was transferred to our tertiary care hospital for further management. On physical exam, her BMI was 24.6 kg/m2. She was oriented to person, but not to place and time. She did not show wasting or hyperpigmentation.
On admission, random serum glucose was 47 mg/dL. Because her random serum glucose levels had been low, she was not started on a 72-hour fast but kept on regular diet. Her capillary glucose levels were checked every 2 hours. Repeat laboratory tests revealed hypoglycemia with a serum glucose level of 30 mg/dL, insulin 15 mIU/L (normal, 2-15 mIU/L), C-peptide 3.62 ng/mL (normal, 0.8-3.1 ng/mL), proinsulin 244 pmol/L (normal, < 18.8 pmol/L) and beta-hydroxybutyrate 0.08 mmol/L (normal, < 0.28 mmol/L).
The patient did not have neuroglycopenic symptoms. She was started on IV dextrose infusion because blood glucose remained less than 70 mg/dL with intermittent serum glucose levels dropping to the 40s. Laboratory testing suggested an endogenous excess insulin consistent with an insulinoma.
After a hand-assisted laparoscopic distal pancreatectomy and splenectomy, the patient experienced rapid resolution of her hypoglycemia. Pathology revealed a well-differentiated neuroendocrine tumor with positive staining for synaptophysin and chromogranin and negative staining for insulin. On follow-up, the patient’s blood glucose levels have remained within normal limits.
Images: reprinted with permission.
Diagnosing, treating insulinoma
The diagnosis of insulinoma is likely if the patient has neuroglycopenic symptoms, a fall in plasma glucose to less than 45 mg/dL (< 2.5 mmol/L), inappropriately elevated beta-cell polypeptides (insulin, proinsulin and C-peptide levels) and a beta-hydroxybutyrate level of less than 2.7 mmol/L. Insulinomas are the most common functioning pancreatic endocrine tumors, but they are rare tumors that occur in one to four people per million in the general population. Insulinomas cause hypoglycemia, and patients present with related autonomic and neuroglycopenic symptoms. Diagnosis is based on endocrine tests confirming hypoglycemia and excess endogenous insulin secretion and imaging procedures.
Surgical resection is the best treatment with a cure rate of 85% to 95%. Tumor localization is an essential step in surgical planning. Multiple noninvasive imaging techniques are available, including transabdominal ultrasonography, CT and MRI. Because insulinomas tend to be small, the sensitivity of transabdominal ultrasound in the localization of insulinomas is poor. CT and MRI can detect 30% to 66% of these tumors. MRI has a slight superiority in the detection of extrapancreatic extensions. Typically, insulinomas are hypervascular. CT imaging will show a significant enhancement compared with normal pancreatic parenchyma during the arterial and capillary phases of contrast bolus (Figure). On MRI, these tumors demonstrate low-signal intensity on T1-weighted images and high-signal intensity on T2-weighted images.
If these noninvasive tests fail to localize the insulinoma, invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling, should be performed and may have superior abilities to localize the tumor. Selective percutaneous transhepatic venous sampling can localize an insulinoma to the head, body or tail of the pancreas, and selective arteriography is also often helpful in localizing insulin-secreting lesions. Nuclear octreotide scans can localize somatostatin receptors on insulinomas in approximately 50% of cases. Preoperative identification of the tumor location allows an uninterrupted surgery, decreasing the probability of reoperation and limiting perioperative complications.
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- Stephanie L. Lee, MD, PhD, ECNU, is an Endocrine Today Editorial Board member, Associate Professor of Medicine, Director of the Thyroid Health Center, Section of Endocrinology, Diabetes and Nutrition. She is associate professor of medicine and director of thyroid health, in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: firstname.lastname@example.org. Lee reports no relevant financial disclosures.
- Ayse Sahin-Efe, MD, is a fellow in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Sahin-Efe reports no relevant financial disclosures.