Mechanism of the disordered physiology involved in the Zollinger-Ellison syndrome

Report of a case
  • Harry Shay
  • Woo Yoon Chey
  • Sumi Mitsudo Koide
  • W. Emory Burnett


A detailed study of the altered gastrointestinal physiology and findings at autopsy in a patient with Zollinger-Ellison syndrome is presented. The results warrant certain considerations with regard to mechanisms involved in the altered physiology.

The importance of the discovery by Gregoryet al. of a gastrinlike substance in the pancreatic tumor of such a patient is obvious in relation to the excessive gastric secretion which was first emphasized in this syndrome. Our results indicate that undue vagal activity may also play a role, in some cases at least.

Data are presented which indicate that the parietal cell mass in some of these patients may be maximally or nearly maximally stimulated at all times.

A rather remarkable effect of adequate anticholinergic and ulcer therapy on the control of the gastric secretion, diarrhea, and ulcer healing is recorded.

It is our belief that the characteristic features of this disease, the fulminant peptic ulcer diathesis, the watery diarrhea with or without excessive potassium loss, and steatorrhea can all be related to the inordinate increase of gastric secretion; that the non-B cell tumor or islet hyperplasia must be very important in the gastric hypersecretion; and that vagal activity can also exert an important influence on this secretion (demonstrated in the case reported above).

Finally, the nonfunctioning parathyroid adenoma found microscopically was of no importance in the patients clinical picture.


Adenoma Gastric Secretion Parathyroid Adenoma Ulcer Healing Watery Diarrhea 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zollincer, R. M., andEllison, E. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas.Ann. Surg. 142: 709, 1955.PubMedGoogle Scholar
  2. 2.
    Sun, David, C. H., andShay, H. Optimal effective dose of anticholinergic drug in peptic ulcer therapy.A.M.A. Arch. Int. Med. 97:442, 1956.Google Scholar
  3. 3.
    Marks, I. N., andShay, H. Augmented histamine test, Ewald test meal and Diagnex test.Am. J. Dig. Dis. (New Series) 5:1, 1960.Google Scholar
  4. 4.
    Shay, H., andSun, David C. H. Stress and Gastric secretion in man. I. A study of the mechanism involved in insulin hypoglycemia.Am. J. Med. Sci. 228:6, 1954.Google Scholar
  5. 5.
    Kay, A. W. Effect of large doses of histamine on gastric secretion of HCl.Brit. Med. J. 2:77, 1953.PubMedGoogle Scholar
  6. 6.
    Shay, H., Sun, David C. H., Chey, W. Y., andO'Leary, D. K. Practical pancreatic function profile for the diagnosis of chronic pancreatic disease.Am. J. Dig. Dis. (New Series) 6:142, 1961.Google Scholar
  7. 7.
    Zollinger, R. M., andCraig, T. V. Ulcerogenic tumor of the pancreas.Am. J. Surg. 99:424, 1960.PubMedGoogle Scholar
  8. 8.
    Maximov, A. A., andBloom, W.A Textbook of Histology (ed. 5), p. 449, Philadelphia, Saunders, 1948.Google Scholar
  9. 9.
    Gregory, R. A., Tracy, H. J., French, I. M., andSircus, W. Extraction of a gastrin-like substance from a pancreatic tumor in a case of Zollinger-Ellison syndrome.Lancet 1:644, 1956.Google Scholar
  10. 10.
    Gregory, R. A., andTracy, H. J. The preparation and properties of gastrin.J. Physiol. 149:70, 1959.Google Scholar
  11. 11.
    Hallenbeck, G. A., Code, C. F., andKennedy, J. C. “Gastrin” of Pancreatic Origin. Sixty-second Annual Meeting of the American Gastroenterological Association. Chicago, May 27, 1961.Google Scholar
  12. 12.
    Zollinger, R. M., andMcPherson, R. C. Ulcerogenic tumors of the pancreas.Am. J. Surg. 95:359, 1958.PubMedGoogle Scholar
  13. 13.
    Summerskill, W. H. Malabsorption and jejunal ulceration due to gastric hyper-secretion with pancreatic islet cell hyperplasia.Lancet 1:120, 1959.PubMedGoogle Scholar
  14. 14.
    Elman, R., andHartmann, A. F. Spontaneous peptic ulcers of duodenum after continued loss of total pancreatic juice.A. M. A. Arch. Surg. 23: 1030, 1930.Google Scholar
  15. 15.
    Dragstedt, L. R., Clark, D. F., andVermeulen, C. Significance of lipocaic in surgery.Ann. Surg. 110:907, 1939.Google Scholar
  16. 16.
    Cox, A. J., andBarnes, V. R. Experimental hyperplasia of the stomach mucosa.Proc. Soc. Exp. Biol. & Med. 60:118, 1945.Google Scholar
  17. 17.
    Meyers, W. C. A study of gastric mucosa in various diseases affecting the upper part of the gastro-intestinal tract.Gastroenterology 10:923, 1948.Google Scholar
  18. 18.
    Cox, A. J. Stomach size and its relation to chronic peptic ulcer.A. M. A. Arch. Path. 54: 407, 1952.PubMedGoogle Scholar
  19. 19.
    Card, W. I., andMarks, I. N. The relationship between the acid output of the stomach following “maximal” histamine stimulation and the parietal cell mass.Clin. Sci. 19:147, 1960.PubMedGoogle Scholar
  20. 20.
    Illingworth, C. F. W. Inborn and extraneous factors in the etiology of peptic ulcer.J. Roy. Coll. Surg. Edinburgh 2:14, 1956.PubMedGoogle Scholar
  21. 21.
    Rudolf, L. E., Dammin, G. F., andMoore, F. D. Intractable peptic ulcer and endocrine adenomas with pituitary amphophilic hyperplasia.Surgery 48:170, 1960.PubMedGoogle Scholar
  22. 22.
    Verner, J. V., andMorrison, A. B. Islet cell tumor and a syndrome of refractory diarrhoea and hypokalemia.Am. J. Med. 25:374, 1958.PubMedGoogle Scholar
  23. 23.
    Donaldson, R. M., Jr., Vom Eigen, P. R., Dwight, R. M. Gastric hypersecretion, peptic ulceration and islet-cell tumor of the pancreas (the Zollinger-Ellison Syndrome). Report of case and review of literature.New Engl. J. Med. 257:965, 1957.PubMedGoogle Scholar
  24. 24.
    Telling, M., andSmiddy, F. G. Islet tumours of the pancreas with intractable diarrhoea.Gut, 2:12, 1961.PubMedGoogle Scholar
  25. 25.
    Shay, H. Etiology of peptic ulcer.Am. J. Dig. Dis. (New Series 6:29, 1961.Google Scholar
  26. 26.
    Shay, H. The pathologic physiology of gastric and duodenal ulcer.Bull. N. Y. Acad. Med. 20: 264, 1944 (2nd Series).Google Scholar
  27. 27.
    Brown, C. H., Neville, W. E., andHazard, J. B. Islet-cell adenoma, without hypoglycemia, causing duodenal obstruction.Surgery 27:616, 1950.Google Scholar
  28. 28.
    Maynard, E. P., andPoint, W. W. Steatorrhea associated wi 3th ulcerogenic tumor of the pancreas.Am. J. Med. 25:456, 1958.PubMedGoogle Scholar
  29. 29.
    Borgström, B., Dahlqvist, G. L., andSjövall, J. Studies of intestinal digestion and absorption in the huma.J. Clin. Invest. 6:1521, 1957.Google Scholar
  30. 30.
    Isselbacher, Kurt J. Discussion Panel—Newer Concepts of gastrointestinal absorption. Fats. Sixty-second Annual Meeting American Gastrointestinal Association. May 26, 1961, Chicago, Illinois.Google Scholar
  31. 31.
    Chey, W. Y., Shay, H., andO'Luary, D. K. Role of pancreas in the intestinal absorption of fat in man. To be reported.Google Scholar
  32. 32.
    Rawson, A. B., England, M. T., Gillam, G. G., French, J. M., andStammers, F. A. R. Zollinger-Ellison Syndrome with diarrhea and malabsorption.Lancet 1:131, 1960.Google Scholar
  33. 33.
    Friedell, H. V., Dickson, D. R., andRydell, J. R. Ulcerogenic tumor of the pancreas.Am. J. Gastroent. 31:58, 1959.PubMedGoogle Scholar
  34. 34.
    Warren, S., andJoslin, F. P. Pathology of Diabetes Mellitus. p. 25. Philadelphia, Lea and Febigar, 1938.Google Scholar
  35. 35.
    Bensley, R. R. Structure and relationships of the Islets of Langerhans.Harvey Lect. 10:250, 1914–15.Google Scholar
  36. 36.
    Barbosa, J. J., Dockerty, M. B., andWaugh, J. M. Pancreatic heterotopia.Surg. Gynec. & Obstet. 82:527, 1946.Google Scholar

Copyright information

© Hoeber Medical Division of Harper & Brothers 1962

Authors and Affiliations

  • Harry Shay
    • 1
  • Woo Yoon Chey
    • 1
  • Sumi Mitsudo Koide
    • 1
  • W. Emory Burnett
    • 1
  1. 1.From the Fels Research Institute and Departments of Pathology and SurgeryTemple University Medical CenterPhiladelphia

Personalised recommendations