Two types of Zollinger-Ellison syndrome: immunofluorescent, cytochemical and ultrastructural studies of the antral and pancreatic gastrin cells in different clinical states

Abstract

SUMMARY In this survey the antral, pancreatic and, where present, the neoplastic gastrin cells, were studied in eight cases of the Zollinger-Ellison syndrome. The antral G cells alone were studied in one case of Z-E syndrome, seven cases of simple duodenal ulcer, and five cases of pernicious anaemia.The Z-E cases were divided into two numerically equal groups. The first group had 'short' histories, high serum gastrin levels, and profound antral G cell hyperplasia. The second group had 'long' histories, relatively lower serum gastrin levels, normal antral G cells, and either pancreatic D cell hyperplasia or gastrinoma.Antral G cell hyperplasia, with maximal gastrin storage and normal serum gastrin levels, was found in the duodenal ulcer cases. Antral G cell hyperplasia with minimal storage and high serum gastrin levels was observed in the cases of pernicious anaemia.On the basis of our findings we propose that there exist at least two distinct types (or perhaps stages) of the Z-E syndrome. Suggestions for their pathogenesis are offered.The combination of gastric hypersecretion, intractable peptic ulceration, and non-insulin-producing pancreatic islet cell tumours was noted by Sailer and Zinniger (1946), Forty and Barrett (1952), and by Strom (1953

Comparative study of the value of the calcium, secretin, and meal stimulated increase in serum gastrin to the diagnosis of the Zollinger-Ellison syndrome.

“…The reason for the marked increase in serum gastrin after a test meal in some ZE patients is not clear. Several mechanisms may be put forward to account for the pronounced meal stimulated increase in serum gastrin in these patients, as direct interaction between food and a tumour originated in the duodenal wall, the release of a gastrin stimulating agent-for example, secretin-from the small intestine and co-existing antral G-cell hyperplasia and pancreatic tumours (Polak et al, 1972 (Korman et al, 1973b;Lamers et al, 1977), excluded gastric antrum (Korman et al, 1972b), non-tumorous hypergastrinaemic hyperchlorhydria (Straus and Yalow, 1975), and postprandial conditions (Thompson et al, 1972b). In patients with achlorhydria and excluded gastric antrum, marked increases in serum gastrin after calcium infusion have been found (Straus and Yalow, 1975;Lamers and van Tongeren 1976).…”

“…In some ZE patients, however, the serum gastrin level may at times be only slightly raised and an overlap with non-ZE patients may be present (Thompson et al, 1972a;Isenberg et al, 1973;Walsh and Grossman, 1975). On the other hand, hypergastrinaemia in the absence of achlorhydria or gastrinoma has been found in patients Received for publication 10 September 1976 with excluded gastric antrum (Korman et al, 1972b), antral G-cell hyperplasia (Polak et al, 1972;Ganguli et al, 1974), non-tumorous hypergastrinaemic hyperchlorhydria (Straus and Yalow, 1975), uraemia (Korman et al, 1972a), postvagotomy (Stern and Walsh, 1973), pyloric obstruction (Feurle et al, 1972), and postprandial conditions (Berson and Yalow, 1972). Provocation tests have been advocated in patients suspected of ZE syndrome with fasting serum gastrin levels of less than 1000 pg/ml (Isenberg et al, 1973) or less than 10 times the normal median (Walsh and Grossman, 1975).…”

Conditional deletion of menin results in antral G cell hyperplasia and hypergastrinemia

“…Although not attributed to a specific genetic defect, pseudo-ZES was characterized in 1972 as hypergastrinemia due to antral G cell hyperplasia without tumors (12,27). Described prior to the positional cloning of MEN1, antral G cell hyperplasia is considered a cause of ZES that can exist in the absence of an actual tumor (4,27).…”

“…Important features of sporadic and MEN1-driven gastrinomas include hypergastrinemia and hypersecretion of gastric acid, resulting in diarrhea and extensive duodenal peptic ulcers, collectively known as the Zollinger-Ellison syndrome (ZES) (17,30,37). Although not attributed to a specific genetic defect, pseudo-ZES was characterized in 1972 as hypergastrinemia due to antral G cell hyperplasia without tumors (12,27). Described prior to the positional cloning of MEN1, antral G cell hyperplasia is considered a cause of ZES that can exist in the absence of an actual tumor (4,27).…”

Gastrin and the ultrastructure of G cells in the fasting rat.

“…These conditions include primary G cell hyperplasia (Polak et al, 1972;Cowley et al, 1973;Ganguli et al, 1974); antral G cell hyperplasia secondary to pernicious anaemia (Creutzfeldt et al, 1971;Polak et al, 1971aPolak et al, , 1973; acromegaly (Creutzfeldt et al, 1971), or hyperparathyroidism (Creutzfeldt et al, 1971;Polak et al, 1971b): and duodenal ulcer (Solcia et al, 1970;Creutzfeldt et al, 1975;1976). Pale or electron lucent granules found within the cytoplasm of G cells in these conditions have been interpreted as the emptied sacs remaining after the release of gastrin from the hormone granules of over-active cells.…”