Insulinoma

Description:

60 year old female presented with episodes of hypoglycemia with glucose in the range of 55 to 63. Her symptoms included night sweats and confusion during the day time for which patient would eat peanut butter with improvement. Symptoms were worse with exercise.

Patient was found to have high insulin level of 20 (normal 3 – 11 mU/L). C-peptide was 3.3 (normal 0.8 – 3.9 ng/mL). Hypoglycemic panel, which included medications that cause hypoglycemia, was negative. CT with pancreatic protocol was performed and it did not show any abnormal lesions in the pancreas suspicious for insulinoma.

Patient was then referred for endoscopic ultrasound of the pancreas. EUS showed a hypoechoic, homogeneous, lobulated lesion in the distal body of the pancreas. The mass was triangulated between the pancreatic duct, splenic artery, and splenic vein without any obvious evidence of vessel involvement. It measured 17.5 mm x 8.1 mm. EUS guided fine needle aspiration was performed using a 25G needle and a total of 3 passes achieved adequate cellularity for interpretation.

Cytopathology from EUS/FNA revealed cytomorphology, immunoprofile, and biochemical hormone levels which were supportive of pancreatic endocrine tumor with stains positive for synaptophysin, chromogranin, and CD56. It was negative for PAS, PAS-D, glucagon and insulin.

Patient was subsequently referred for surgery. The tumor was identified in the body of the pancreas and traversed in the anterior/posterior direction. The lesion was enucleated and the pancreas re-approximated.

Final pathology from surgical specimen revealed a well-differentiated 1.6 cm lesion confined to the pancreas without lymphovascular space or perineural invasion. The insulin immunostain was diffusely positive, proving that it was indeed an insulinoma.

Insulinomas are rare pancreatic islet cell tumors. Most insulinomas are solitary and benign. The rule of 10s states that 10% are multiple, 10% are malignant, 10% are associated with MEN1, and 10% are ectopic. Biochemical diagnosis is made by inappropriately high insulin levels during spontaneous or induced hypoglycemia. Then, tumor is localized using tests such as CT, MRI, transabdominal ultrasonography, 111-In-pentetreotide imaging, fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-DOPA PET), EUS, and selective arterial calcium stimulation. Transabdominal ultrasound and CT are usually the initial tests. Anderson et al reported that EUS had an overall sensitivity of 93 percent and specificity of 95 percent for pancreatic neuroendocrine tumors.[1] According to R?sch et al, in patients who had negative transabdominal ultrasound and CT scans, EUS detected endocrine tumors in the pancreas with high sensitivity (82 percent) and specificity (95 percent).[2]

Surgery is the treatment of choice and includes a variety of techniques depending on the extent of disease and the experience of the surgeon. Medical therapy to control symptomatic hypoglycemia for patients in whom insulinoma was not detected during surgical exploration and for those who are not surgical candidates includes diazoxide, octreotide, lanreotide, verapamil, and phenytoin. A few surgical and radiologic therapies are available for metastatic disease to the liver.
Our patient recovered well from surgery and ceased to have hypoglycemic episodes.

References:
1. Anderson MA, Carpenter S, Thompson NW, Nostrant TT, Elta GH, Scheiman JM. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol. 2000;95(9):2271.

2. R?sch T, Lightdale CJ, Botet JF, Boyce GA, Sivak MV Jr, Yasuda K, Heyder N, Palazzo L, Dancygier H, Schusdziarra V. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. 1992;326(26):1721.

Contributed By:

Charles Chaya, MD, Kaiser Permanente Riverside Medical Center

Albert Ko, MD, Kaiser Permanente Riverside Medical Center

Mark Taira, MD, Kaiser Permanente Riverside Medical Center

Jane Tongson-Ignacio, MD, Southern California Permanente Medical Group Regional Laboratory

Brian S. Lim, MD, Kaiser Permanente Riverside Medical Center