Zollinger-Ellison syndrome: Revelation of the gastrinoma triangle

Abstract

Zollinger-Ellison syndrome is a complex condition in which one or more tumors form in the patient's pancreas or upper duodenum. These tumors, called gastrinomas, secrete excessive amounts of gastrin, and almost all develop ulcers. The vast majority of gastrinomas are present within the “gastrinoma triangle,” which is composed of the porta hepatis, duodenal sweep, and pancreatic head. As surgery remains the treatment of choice, localization of the primary lesion is often challenging but essential. We present a 50-year-old man with a tentative diagnosis of Zollinger-Ellison syndrome. His In-111 pentetreotide scan, fused onto a Tc-99m abdomen image, revealed an avid lesion adjacent to the duodenal loop. Operative resection was performed, and a primary pancreatic gastrinoma was diagnosed by immunohistochemical staining. The neuroendocrine tumors have somatostatin receptors upon them. Therefore, a penteteotide scan, using In-111 radiolabelled somatostatin analogues, is the current technique of choice. This dual-isotope display permits a visual perception of anatomic landmarks around the lesion.

Introduction

Zollinger-Ellison syndrome is a rare disorder caused by a tumor called a gastrinoma. The tumor secretes the hormone gastrin, which causes excess production of gastric acid, leading to severe recurrent ulcers of the esophagus, stomach, duodenum, and jejunum. The rarity of the syndrome may render the diagnosis difficult to make, especially since most radiologists are not aware of this entity. About 85% to 90% of gastrinomas are present within the “gastrinoma triangle.” When the Zollinger-Ellison syndrome is suspected, physicians have to try to identify the tumor in the pancreas or the bowel. An In-111 penteteotide scan is the current technique of choice. However, even using the technique of SPECT/CT, the location may be missed or masked by peripheral anatomic structures in the gastrinoma triangle. We hope to raise awareness of the disease and of a dual-isotope display as the method to identify the gastrinoma in the gastrinoma triangle.

Case report

A 50-year-old man was admitted because of abdominal cramps, vomiting, and watery diarrhea with up to 10 bowel movements. His medical history included 10 years of peptic ulcer disease, abdominal pain, and diarrhea, leading to a presumptive diagnosis of irritable bowel disease. A year earlier, he had an episode of upper gastrointestinal bleeding. For the prevention of relapsing peptic ulcer, he had been taking Nexium® (esomeprazole, a proton-pump inhibitor) thereafter. Esophagogastroduodenal endoscopy (performed for investigation of the gastric symptoms) revealed diffuse erosive esophagitis and duodenal ulcer, and absence of Helicobacter pylori infection. Colonoscopy was reported as normal. A gallium-67 scan, made for a tumor survey, failed to exhibit active lesions. His baseline gastrin levels were measured at 900 pg/mI, with an increase to more than 1200 pg/mI after an IV secretin test. Further laboratory evaluation excluded multiple endocrine neoplasia type 1 syndrome.

A further approach to investigating the etiology of the hypergastrinemia (an In-111 pentetreotide scan) showed an avid focus at the epigastrium (Fig. 1, open arrow), besides physiologic uptake in the kidneys and the spleen. For ease of lesion mapping, the patient was asked to drink a mouthful of water with Tc-99m pertechnetate added. Dual-isotope planar images were acquired simultaneously, centering on the two In-111 photopeaks (170 & 245 keV) and on the Tc-99m photopeak (140-keV). The Tc-99m abdomen images were displayed to be the background maps (Fig. 2, A & B). The In-111 image was superimposed onto a Tc-99m image (Fig. 2, C & D), which showed that the pathologic focus was next to the duodenum and inside the gastrinoma triangle (1).  Subsequent CT revealed a 2.7×2.4-cm, lobulated, enhancing lesion at the pancreas head (Fig. 3). Operative resection was performed. Pathological examination revealed a gastrin-producing neuroendocrine tumor. The tumor cells were immunoreactive with chromogranin-A, synaptophysin, and gastrin. The patient's serum gastrin level returned to normal (60 pg/ml) at 6-week followup, consistent with a surgical cure of Zollinger-Ellison syndrome.

Figure 1.

An In-111 pentetreotide octreotide scan showed an avid focus at the epigastrium (open arrow), besides physiologic uptake in the kidneys and the spleen.

Figure 2.

Pentetreotide imaging plus abdomen scintigrams. The patient was asked to drink a mouthful of water with Tc-99m pertechnetate added. Dual-isotope planar images were acquired simultaneously, centering on the In-111 photopeaks and on the Tc-99m photopeak. The Tc-99m abdomen images were displayed to be the background maps (A and B). The In-111 image was superimposed onto a Tc-99m image (C and D), which showed that the pathologic focus was next to the duodenum and inside the gastrinoma triangle.

Figure 3.

Abdomen CT axial (A) and coronal (B) images showing a 2.7×2.4-cm, lobulated, enhancing lesion at the pancreas head (open arrow).

Discussion

Gastrinomas are an integral part of the Zollinger-Ellison syndrome (1, 2). The tumors produce large amounts of gastrin, triggering gastric acid hypersecretion, refractory peptic ulcers, and diarrhea. Recent data suggest that 65% of gastrinomas are malignant, and up to 30% to 40% of patients will have evident metastatic disease at initial presentation (3, 4, 5), requiring accurate preoperative localization of the tumor (6). Gastrinomas are postulated to originate from stem cells of the ventral pancreatic bud (7), as a result of aberration of neuroendocrine cells during normal embryonic rotation of the ventral pancreas (7, 8). Consequently, 85% to 90% of gastrinomas lie within the gastrinoma triangle (9), comprising the porta hepatis, duodenal sweep, and pancreatic head (Fig. 3D).

Functioning neuroendocrine tumors are characterized by presenting symptoms and signs in their early stages, while the lesions are small. Precise localization of small foci is difficult. Somatostatin receptors are found on 80% of gastrinomas. Therefore, a pentetreotide scan, which uses an analog of somatostatin, has successfully localized these neoplasms (primary or nodal metastases) in up to 78% to 86% of cases (10, 11, 12). Gibril et al. studied 80 patients and found that CT, MRI, or angiography identified extrahepatic gastrinomas in 28% to 31% of patients, and ultrasound detected extrahepatic tumors in 9% of patients (13). The role of pentetreotide scan is not just for localization of primary lesions, but also for screening of metastases, and monitoring therapeutic response (13).

In the current era of multimodality imaging, SPECT/CT plays an important role in localizing small lesions. One major drawback of SPECT/CT imaging is additive ionizing radiation from the CT procedure. The estimated radiation dose of CT from SPECT/CT is variable because of the many factors involved. Briefly, for one SPECT bed position, the effective dose to the chest and abdomen is around 4 mSv. In case of a CT for a two-bed SPECT/CT, the appropriate effective dose values are added together (14). Besides, the artifacts caused by any movement of the patient or bowel movement would reduce the sensitivity, especially for small pancreatic tumors. Combining Tc-99m MDP and In-111 pentetreotide studies into a single display, which showed more information, has previously been suggested (15). Similarly, our technique does not increase time consumption or significant radiation delivered to the patient, and can be easily implemented on any nuclear medicine workstation with minimal data acquisition. It is a rather straightforward display that permits a visual perception of anatomic landmarks around the lesion.