Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1

Abstract

Zollinger-Ellison syndrome (ZES) is the most common symptomatic pancreatic endocrine tumour in patients with MEN-1. Besides the treatment of the usual endocrinopathies seen in patients with MEN-1, the treatment of the ZES requires attention be paid to controlling the gastric acid hypersecretion, to dealing with the gastrinomas per se which are malignant in 18-60% of cases, and to the diagnosis and treatment of gastric carcinoid tumours, that are increasingly seen in these patients. In this article the current management of each of the areas is reviewed and what is known or uncertain discussed, based on our studies at the NIH and data from others. Data from 231 patients including 45 with MEN-1 and 186 without MEN-1 is contrasted in this report. Gastric acid hypersecretion has been controlled in all patients medically with MEN-1 and ZES at the NIH for up to 22 years. The current drugs of choice are H ϩ -K ϩ ATPase inhibitors and twice a day dosing is recommended. Periods of parenteral drug therapy (surgery, etc.) and pregnancy require important modifications. The appropriate surgical therapy of the gastrinoma is controversial. Eighty per cent of patients have a duodenal gastrinoma and 20-30% have a pancreatic tumour. Recent studies suggest gastrinoma enucleation combined with duodenotomy rarely results in cure. Aggressive surgery (Whipple resection) can result in cure of gastrinoma but effect on survival is unclear.There are important differences in gastrinoma location, extent, and percentage with aggressive disease in patients with or without MEN-1, which are discussed. Confusion has occurred because of lack of information on the natural history of the gastrinoma compared to the other pancreatic endocrine tumours that occur in MEN-1 and survival data from patients with and without MEN-1 is contrasted. The occurrence of gastric carcinoids in patients with and without MEN-1 with ZES is contrasted and the areas of certainty and disagreement reviewed.

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

“…MEN1-related dpNETs are seen one to two decades earlier than their sporadic counterparts (Jensen 1998, Nikfarjam et al 2008, Anlauf et al 2009, Crippa et al 2012, Singh et al 2012. Insulinomas have the lowest age of onset (patients are usually in their twenties to thirties at diagnosis), patients with gastrinomas and NF-pNETs are usually diagnosed in their thirties (Jensen 1998, Cougard et al 2000, Triponez et al 2006a, Sakurai et al 2012b.…”

“…Insulinomas have the lowest age of onset (patients are usually in their twenties to thirties at diagnosis), patients with gastrinomas and NF-pNETs are usually diagnosed in their thirties (Jensen 1998, Cougard et al 2000, Triponez et al 2006a, Sakurai et al 2012b. At the age of 60, the penetrance of gastrinoma is significantly higher in men (55%) compared with women (33%), while the other dpNET types do not show gender differences (Goudet et al 2011).…”

Neuroendocrine tumors of the small bowels are on the rise: Early aspects and management

“…Because the duodenal NETs are almost invariably multiple, frequently small, and 40%-70% have metastasized at diagnosis, without aggressive surgery which is not recommended, MEN1 patients can generally not be cured by surgery [8,9,63] . Therefore, the ZES in MEN1 has to be treated long-term and effectively with a proton pump inhibitor [64] . Furthermore, the presence of hyperparathyroidism in these patients can make medical control of the gastric hypersecretion more difficult with more frequent and higher PPI doses needed [64,65] .…”

“…Therefore, the ZES in MEN1 has to be treated long-term and effectively with a proton pump inhibitor [64] . Furthermore, the presence of hyperparathyroidism in these patients can make medical control of the gastric hypersecretion more difficult with more frequent and higher PPI doses needed [64,65] . It is therefore recommended that the hyperparathyroidism be treated appropriately (surgical resection of at least 3.5 glands) and the patient followed carefully because it can relapse [64,65] .…”

“…Furthermore, the presence of hyperparathyroidism in these patients can make medical control of the gastric hypersecretion more difficult with more frequent and higher PPI doses needed [64,65] . It is therefore recommended that the hyperparathyroidism be treated appropriately (surgical resection of at least 3.5 glands) and the patient followed carefully because it can relapse [64,65] . With this in mind, MEN1/ ZES patients should be treated in specialized clinics; the surgical option should be considered only in specialized centers and only after an interdisciplinary discussion of the individual patient.…”