Recurrent episodes of confusion

Issue: June 2008

ByAngela M. Leung, MD

ByStephanie L. Lee, MD, PhD, ECNU

A 54-year-old woman presented to the emergency department with dizziness, slurred speech and weakness six hours following a noontime meal. She appeared mildly confused and lethargic. A capillary blood glucose level was 12 mg/dL. Her symptoms resolved after the intravenous administration of one ampule of D50. The remainder of a routine complete blood count and chemistry panel were all unremarkable, and she was admitted to the hospital for further evaluation.

She reported a two year history of similar episodes, characterized by weakness and confusion, which were unrelated to meals or physical activity. She reported three hospital admissions within the last year for recurrent hypoglycemia. She was told to eat small, frequent meals, test her capillary blood sugar three times a day, and wear a medical alert bracelet for low blood sugars. Because of her frequent meals, she reported an approximate 60 lb weight gain over the preceding two years.

She denied any personal or family history of diabetes or use of oral hypoglycemic medications or insulin. Review of systems was negative for prominent headaches, palpitations, perspiration, cutaneous flushing or psychiatric disorders. She denied any tobacco, alcohol or illicit drug use.

On physical exam, the patient’s blood pressure was 122/77 mmHg, pulse was 102/min and regular, and BMI was 32. Her thyroid was not enlarged and there were no palpable nodules. She had a steady gait and was oriented to person, place and name. The findings on the remainder of her physical exam were normal. Laboratory measurements revealed serum TSH of 0.85 mIU/L, a negative urine sulfonylurea level and morning serum cortisol of 14.3 mcg/dL.

Angela J. Leung

Stephanie L. Lee

A supervised 72-hour fast was performed and stopped because of neuroglycopenic symptoms after 12 hours with a capillary blood glucose of 10 mg/dL. Immediate laboratory testing revealed a blood glucose 51 mg/dL, insulin 72 µIU/mL (reference, 0-16 µIU/mL), insulin autoantibody <1 U/mL (<1 U/mL), C-peptide 4.2 ng/mL (0.8 to 3.1 ng/mL), proinsulin 39 pmol/L ( <18.8 pmol/L), and â-hydroxybutyrate 0.08 mmol/L ( <0.28 mmol/L). The fast was terminated with the collection of these laboratory measurements.

Our patient fulfilled Whipple’s triad (documented hypoglycemia, symptoms of hypoglycemia, resolution of symptoms with the administration of glucose) upon presentation, and combined with the results of the 72-hour fast, our suspicion was high for an insulin-mediated hypoglycemia. We performed pancreatic imaging for pre-surgical localization of an insulinoma. A transabdominal ultrasound, contrast-enhanced abdominal CT and octreotide scans were all unremarkable. An endoscopic ultrasound delineated a 0.37 cm x 0.34 cm hypoechoic mass located at the junction of the body and tail of the pancreas (Figure 1A). This was thought to be an insulinoma and the patient underwent surgical exploration. The surgeon palpated a mass in the tail of the pancreas that was much larger than preoperative imaging, and an intraoperative ultrasound demonstrated a 1.3 cm x 0.8 cm x 0.8 cm hypoechoic, heterogeneous mass with a peripheral hypoechoic rim and increased vascularity by Doppler located in the tail of the pancreas (Figures 2A and 2B). In addition, an anechoic, avascular 0.4 cm cyst was found in the body of the pancreas (Figure 1B). The 1.3 cm mass was enucleated with the decision not to remove the small cyst. The pathology specimen demonstrated a well-circumscribed 2 cm x 1.5 cm x 1.8 cm mass that positive by immunohistochemistry for chromogranin, synaptophysin and insulin consistent with an insulinoma. The glucagon immunostain was negative.

Figure 1. Ultrasound of pancreatic cyst. (A) Endoscopic ultrasound showing a 0.4 cm hypoechoic nodule in the tail of the pancreas. (B) Intraoperative ultrasound showing a 0.4-cm hypoechoic, avascular cyst in the tail of the pancreas. None of the preoperative imaging revealed the location of the pancreatic insulinoma. The pancreatic mass identified by preoperative endoscopic ultrasound, in retrospect, was a false positive test.

Figure 2. Intraoperative ultrasound of the pancreatic insulinoma. (A) Transverse view of the insulinoma showing peripheral hypervascularity by Doppler analysis. (B) Sagittal view of the insulinoma.

Figure 3. Insulinoma. (A) Intraoperative identification of the mass (as pictured between the forceps) in the tail of the pancreas. (B) Insulinoma after enucleation from the tail of the pancreas.

Images courtesy of Boston Medical Center

The choice for localization imaging depends on the expertise of each individual institution and may include abdominal spiral CT, transabdominal and endoscopic ultrasonography, arteriography, octreotide scintigraphy, and positron emission tomography. As in this case, imaging can be unrevealing for an insulinoma. Selective arterial calcium stimulation of the gastroduodenal, superior mesenteric, and splenic arteries with concurrent measurement of insulin levels from the right hepatic vein may be used when a tumor is unable to be localized. If a discrete mass is identified, enucleation should be the procedure of choice, though distal pancreatectomy may be required in tumors located in the tail of the pancreas. Insulinoma tumors are benign in over 90% of all cases, and successful resection of benign tumors results in the complete resolution of preoperative neuroglycopenic symptoms and normal long-term survival.

Our patient is now one year after successful excision of the benign insulinoma and continues to be symptom-free with normal fasting and random glucose levels.

Angela M. Leung, MD, is a Fellow in Endocrinology at Boston Medical Center. Stephanie L. Lee, MD, PhD, is an Associate Professor of Medicine at Boston University School of Medicine and Director of Endocrine Clinics at Boston Medical Center.

For more information:

Service FJ. Hypoglycemic disorders. New Engl J Med. 1995;332:1144-52.

Grant CS. Insulinoma. Surg Oncol Clin N Am. 1998;7:819-44.