CASE RECORD

Antral cell hyperfunction associated with chronic

ATILLA ERTAN. MD, MARTINS. LITWIN, MD, ROBERT A. HAMMER. MD, PAUL VEGA. MD

NTRAL GASTRIN CELL HYPERFUNC­ ABSTRAC T: Th is report describes a patient with antral gastrin cell hyperfunction A tion resembling the Zollinger­ who also had pancreatic pseudocy:m and partial common obstruction sec­ Ellison sy ndrome (ZES) was first de­ ondary ro ch ronic pancreatitis. A 60-year-old female had a th ree-month h istory of scribed in 1972 (I) and subsequentl y wor~ening epigastric discomfort with episodes of , vomiting and weigh t loss. reported by others (2-8). O ther terms The patient had no history of peptic ulcer d isease and no ulcers were demonstrated such as 'ZES type 1· (2) and 'pseudo-ZES' during diagnostic work-up. Baseline fasti ng serum were 715 and 1000 pg/ml [normal 50 to 170 pg/ml). These decreased to 515 pg/ml during an intravenous ( 5 ). have been used fo r this syndrome. secretin test and increased up to 2155 pg/ml after a protein meal test. The patient Since the volume density of antral G cells also had . multiple pancreatic and a partial common has been found to be both increased bile duct obstruction. Tru ncal vagotomy and antrectomy for antral gastrin cell (2,5.7) a nd normal (8), and since an hyperfunction. Roux-en-Y cyscjejunostomy for pancreatic pseudocysts and chole­ increased G cell density can occur in dochojejunostomy for stricture were performed. Three mon ths other conditions (9- 1l ). the term an tral after the operation. the patient was symptom-free and fasting serum gastrin levels at gastrin cell hyperfunction appears to be one week, two months and three months after the surgery were ll, 40 and 50 pg/ml, most appropriate ( 12). respectively. Can J Gasti:oe nte rol 1988;2(3):123-1 26. The incidence of this e ntity is un­ Key Wo rds: A nrral gasrrm cell hyperJ1me11on. Chronic pancreaii11s known, but with refinements of diagnos· tic procedures, includ ing serum gastri n Deparrmenrs of Medicine, Surgery and Pmhology, Ttilane U111t1ers1Cy Medical School, response to protein meal and intravenous ~ew Orleans, Loumana secretin. its recognition is increasing as Correspondence and reprints: Dr Ar ilia Er ran. Tulane Un iversity School of Medicine, Section of Gasrroenr.erology, 1430 Tztlune A1•en11e, New Orleans, Louisiana 70112. USA. Tclephone awareness of its possibiliry is appreciated. 1504) 588-5329 T he clinical significance of differentiat­ Recen•ed for Jiublicmwn June 1. 1988 Acee/ired July 21. /988 ing between various causes of hypergas-

Vol. 2 No. 3. September 1988 123 ERTAN ec a/ trincmia is obvious because their man­ or endocrinopathy. vatcd baseline serum gastrin concentra­ agements arc quite different. The clini­ Physical examination was unremarkable tions (715 and 1000 pg/mL) decreased cal associations of antral gastrin cell except for mid-epigastric tenderness to (down to 515 pg/ml) after intravenous hyperfunction include basal hypcrgas­ palpation. secretin; there was an exaggerated in­ trinemia, an exaggerated gasrrin response The following laboratory data were crease (up to 2155 pg/ml) after the pro­ to a protein meal. peptic ulcer disease reported on admission: hemoglobin 14. l tein meal (Figure I). Serum concentra­ and the absence of . The pur­ gl 100 ml, hematocrit 41.3%. white blood tions of prolactin ( l l.2 pg/ml), pancre­ pose of chis report is to presen t a patient cell count 5600/mml with normal dif­ atic polypeptide (253 pg/ml) and para­ with antral gastrin cell hyperfunction ferential, urinalysis normal, stool exam thyroid hormone (25 µl Eq/ml) were without peptic ulcer disease who also had negative for occult blood and negative within normal limits. pancreatic pseudocysts and a partial Sudan-Ill reaction. Blood urea nitrogen, Because of the low p H value of gastric common bile duct obstruction second­ total serum protein, albumin, liver en­ aspirate during the initial esophagogas­ ary co chronic pancreacitis of unknown zymes, alkaline phosphatase, bilirubin, troduodcnoscopy and the patient's sig­ etiology. electrolytes, calcium concentrations and nificant epigastric discomfort, a gastric lipid profile in scrum, serum and uri­ secretory srudy was deferred. However, CASE PRESENTATION nary concentrations were within the scrum grou p I pepsinogen concen­ In May 1987, a 60-year-old white fe­ normal limits. tration was 200 ng/ml (normal, 25 to male was admitted to hospital after the Stimulation tests for scrum gastrin lOO ng/ml) and was consistent with sudden onset of acute, sharp, scabbing were performed by th e intravenous i n creascd gastric secretory capacity. mid-epigastric pain. She had previously administration of secretin 2 U/kg (Phar­ Endoscopic retrograde cholangiopan­ been completely asymptomatic and the macia, Inc) and by administration of a creatography (ERCP) showed a partial present complaints had developed fo l­ protein meal. Fasting venous blood sam­ obstruction of the intrapancrcatic por­ lowing a heavy meal. The patient was ples were taken through an intravenous tion of the distal common bile duct. Also diagnosed as having acu te pancreatitis catheter 15 and 5 mins before secretin noted were dilatation of the proximal and medical management was begun. injection and then 1, 2, 5, 10, 15, 30 and common bile duct (approximately 21 Because of epigastric discomfort, eso­ 60 mins after the injection. mm in diameter) a nd intrahepatic bile phagogastrod uodenoscopy was per­ Immediately after completion of the ducts (Figure 2). The main pancreatic formed. A 'beefy appearing gastric secrctin test, the patient ate a test meal duct was diffusely narrowed and wa~ mucosa wit', edematous folds' was de­ consisting of three eggs, two slices of more prominent in the body and the scribed. There was no ulcer or gastric bacon, two slices of toast and 8 oz of milk tail. Contrast extravasation during ERCP oudet obstruction. Gastric aspirate pH containing 2% butterfat. The meal con­ was interpreted as representing a pseu­ was 1.0 by indicator paper and fasting tained 34.5 g protein, 26.6 g fat and 4 Ll docyst in che tail of the . serum gastrin concentration was 1800 g carbohydrate (5). Blood samples were Because of th e patient's persistent pg/mL. An abdominal computerized taken 0, 5, 10, 15, 30 and 60 mins after symptoms, surgical exploration was per­ tomography (CT) scan showed a mass starting the meal. Serum gastrin was formed on August 17. 1987. No intra­ in the tail of the pancreas. Seven days measured in all blood samples using a abdominal gastrinoma was found. The after admission symptoms had resolved radioimmunoassay technique which spe­ pancreas was noted co be firm and and the patient was discharged on ci fi cally measures physiologically active appeared chronically inflamed. T here cimetidine 800 mg bid and antacids. A gastrin, both G-17 and G-34 (13). Ele- were two pscudocysts in the body and follow-up serum gascrin concentration two weeks later was above 1000 pg/ml and repeat abdominal CT scan showed Secretin (2u/kg IV) Protein Meal Antrectomy + Vagotomy persistence of the previously noted pan­ creatic mass. The patient was referred 2000 co Tulane University Medical Center E where she was admitted on August 13, Cl 1987 fo r further study and treatment. .e ·.:C: f7 At the time of admission che patient .; 1000 described post prandial epigascric distress C)"' E associated with a 30 lb weigh t loss over :, t the previous three months even though CJ') there had been no change in he r usual 0 15 30 60 15 30 1 14 good appetite. There was no vomiting 60 L8 or and no history of peptic ulcer Time (mins) Postoperative Period (weeks) d isease or pancreatic disease. She also Figure 1) Sernm gascrin response to che sumulation cescs and a{cer surgery. Elevaced baseline serum denied alcohol and tobacco use and drug gascrin decreased co 515 pg/mL a{cer intravenous secrecin rest and increased up co 2155 p1;/mL a{cer a abuse. There was no fami ly history of procein meal cest. The serum gascrm leveLI returned co normal limus after ancreccomy and i•agowmy

124 CAN JGASTROENTEROL Antral gastnn cell hyperfunc tion

viously been treated by vagocomy. a con­ dition known co result in G cell hyper­ plasia. The present patient had not had a prior vagotomy to account for this. The authors believe that the patient had antral gastrin cell hypcrfunction with a fasting hypergastrinemia and an exag­ gerated gastrin response to a protein meal. Moreover, the dramatic return of hypcrgastrincmia to normal after antrec­ tomy and vagoromy suggested that the ant rum was the sole ~ource of the excess scrum gastrin. This is the first reported ca~e o( antral gasrrin cell hyperfunction associated with chronic pancreatitis and its complica­ rions, such as p:mcrcmic pscudocyscs and a partial common hile duct obstruction. Fasting and postprandial hypcrgastrin­ cmia have been ohserved in patients with chronic pancrcatitis ( 14, I5). This hypcr­ gastrincmia may be secondary to chron­ irnll y reduced gastric acid secretion ( 14). On the other hand, a more recent study Figure 2) £11Ju1co/nc reoograJe cholan1f.10/Ja11crcawgraphy .1howeJ a ,mooch purcwl 5!1'lCCt1re of chc d1scal com mun /11/e d11ct cc>mbrneJ il'llh /JU.IC scncwre Jilacaticm of clie common bile clucc and mcrulie­ indicated that patients with severe pan­ pacic hile cl11cr., The main Jnrncreuric duce tl'as dijf11sel:, nmroH'ed crcmic insufficiency frequently have had gawic acid hypcrsccretion ( 15). However, none of the previous studies showed tail The following procedures were pcr­ patients have been mostly male, rcb­ basal gastrincmia above 400 pg/ml in tormcd: pancreatic biopsy; Roux-cn-Y tivcly young (oldest 58 years old) and these raticnts ( 14.16). This association pancrcaricocyscjej u nostomy; cholecystec­ have always had peptic ulcer disease with appears co be coincidental in the pres­ tom y: Roux-en-Y choledochojeiuno­ acid hypcrsecretion. moderate fasting ent case. Despite significant partial stric­ stomy. and antrcctomy and vagotomy. hypcrgastrincmia with an exaggerated tun: of the disrnl common bile duct com­ Pathologic exam of the pancreatic biopsy n.:sponse to ,1 standard rest meal and a bined with dilatation of extra- and intra­ \\'as consistent with chronic p:rncreaci­ minimal gastrin response to intravenous hepatic bile ducts, the patient's liver func­ tis. The gastric ancrum showed chronic sccrccin ( 1-8 ). Some of the patients in tion tests were within normal limits. hypertrophic . pancreatic acinar­ chc original study ( l ). as well as chose This is the oldest patient reported with type and intestinal metaplasia with G cell reporccd hy other authors (4. 5 ), had pre- antral gastrin cell hyperfunction ( 1-8, l2). hypcrplasi;i . The gallhladder showed chronic cholecystills with cholesterolosis. The patient's postorcrntive course wa, L'hype rsecr etion d e gastrine a ntrale associee a la pancreatite uneven tfu I. The pntieni was discharged chronique on August 26. 1987 and h:is remained RESU ME: Ce rapport decrit une patience souffrant d 'une hypersecretion de gastrine well for at least the last five months and au nivc;1u de l'antre, chez qui on a cgalcmcnt dcccle des pscudokystcs pancreatiques i now on pancremic cn:ymc therapy and ct une ohstruction secondairc particlle des canaux biliaires suite a unc pancrcatite has gained 20 lbs. Fasting scrum gasrrin chroniquc. Agee de 60 ans. la patience souffrait dcpuis trois mois de malaises levels at the end of the first postopera­ epig;1striqucs qui cmpiraicnt ct qui s·accompagn aicnt de nau ccs. de vomisscmcnts tive week. two months and three months ct cl' amaigrisscmcn c. Ellen 'avai t jamais eu d 'u lee res pepciques ct u n examen a pprofond i after surgery were 11. 40 and 50 pg/ml. n'cn rcvela aucun. La gastrinem1c a jcun eta it de 715 Ct LOOO pg/ml (niveau normal respectively. de 50 a 170 rg/mll. diminuant jusqu'a 5 l 5 pg/ml du rant un test de secrctinc par iv ct augmcntant jusqu'a 2155 pg/ml aprcs un repas-tesc procc iniq uc. Le chirurgicn a DISCUSSION cffcccuc unc vagacomic tronculaire pour corriger l'hypersecretion de gastrine antrale, Zollinger-Ellison syndrome has been une kysto-jejunoscomie de Roux-cn-Y pour lcs pseudo-kystes pancreatiqucs ct unc choledocho-jcjunostom1c pour l'obscruccion secondaire parcielle dcscanaux biliaires. classified into two types; type 1, due to Trois mois plus card, cous Jes symptomcs avaient disparu ct Jes niveaux de gastrinemie antral gastrin cell hypcrfunction and type ajeun ccaicn1 de 11. 40 cc 50 pg/m L rcspcccivcmcnt. une scmaine. deux mois ct trois 2, due co a gastrinoma (I). Characteris­ moi~ a pre, !'intervention. tically. antral gasrrin cell hyperfunction

Vol. 2 No. ,. September l98t'l 125 ERTAN er al

Although the previously reported pa­ function patient was reported co have G cells co stimulation by a protein meal tients had a strong family history of pep­ had no peptic ulcer disease (5). and the failure of an in travenous secre­ tic ulcer disease among first degree rela­ Antral gastrin cell hyperfunction tin injection to cause an elevation of this tives and had a form of peptic ulcer chat might result from abnormal or excessive patient's scrum gastrin level supports was recurrent and resistant to medical trophic factors, excessive neurogenic Friesen's hypothesis (5) chat antral gas­ management, the present patient had stimulation or an inappropriate physio­ trin cell hyperfunction is a primary neither previous nor present peptic ulcer logic response. Although the pathogen­ pathologic abnorrualicy ofG cells and not disease nor a family history of ulcer dis­ esis of primary G cell hyperplasia re­ merely an example of a physiologically ease. One ocher antral gascrin cell hyper- mains co be elucidated, the response of inappropriate function.

5. Friesen SR. Tomita T. Pseudo-Zollinger­ 1978; 13: 199-203. ACKNOWLEDGEMENTS: The authors Ellison syndrome. Hypergastrinemia, 11. Nielsen HO, Halken S, Lorentzen M. thank Mrs April E.T. Dembrun and Mrs hyperchlorhydria without tumor. Ann Quantitative studies of the gamin Andrea A. Janssen for their secretarial assis­ Surg 1981; 194:481-93. producing cells of the human antrum. tance. This work was supported by Gastro­ 6. Keu ppens F. Willems G, De Graef J, A methodological study. Acta Pacho! enterology Research Fund H530569. et al. Antral gastrin cell hyperplasia in Microbial Immunol Scand (A) patients with peptic ulcer. Ann Surg 1980;88:255-61. 1980; 191:276-81. 12. Creutzfeldt W. Gastrointestinal peptides REFERENCES 7. Lewin KJ, Yang K, Ulich T, ElashoffJD. - role in pathophysiology and disease. I. PolakJM, Stagg B, Pearse AGE. Two Walsh J . Primary gascrin cell ScandJ Gastroenrerol 1982;77 types of Zollinger-Ellison syndrome: hyperphsia: Report of five cases and a (Suppl 1):4-20. lmmunofluorescent, cytochemical and review of the literature. Am J Surg 13. Russell RCG. Bloom SR, Fielding LP. ultrastructural studies of the antral and Pathol 1984;8:821-32. Bryant MG. Current problems in the pancreatic gastrin cells in different 8. Lamer, CBH. Ruland CM, Joosten measurement of gasrrin release A clinical states. Gut 1972; 13:501-12. HJM. et al. Hypergastrinemia of antral reproducible measure 0f physiological 2. Cowley AJ, Dymock IM, Boyes BE, et al. origin in duodenal ulcer. Dig Dis Sci gastrin release. Postgrad Med J Zollinger-Ellison syndrome type I: 1978;23:998-1002. 1975;52:645-50. Clinical and pathological correlations in 9. Royston CMS. PolakJM. Bloom SR, 14. Regan PT, MalagcladaJR, OiMagno EP. a case. Gut 197 J; 14:25-9. ct al. G-cell population of gastric antrum, Go VLW. Postprandial gastric function 3. Gray GR. Gillespie G. Gordon l. plasma gastrin and gastric acid secretion 111 pancreatic insufficiency. Gut Extragastric gastrinoma or G-ccll in patients with and without duodenal 1979;20:249-54. hyperplasia of the antrum? The ulcer. Gut 1978; 19:689-98. 15. Gullo L, Corinaldesi R. Casadio R. preoperative diagnosis in a case of 10. Stave R. Brandtzaeg P. lmmunohist0· er al. Gastric acid secretion in chronic hypergastrinaemia. Br J Surg chemical 111vestig::ttion of gasmn pancreatitis. Hcpatogastroe n terology 1976,63:596-8. producing cells (G-cell,). Estimation of 1983 ;30:60-2. 4. Ganguli PC. PolakJM, Pearse AGE, antral density. mucosa! distribution and 16. Gullo L, Vczzadini P. Ventrucci M, Elder JB. Hagerty M Antral ga,trin cell t0rnl mass of G -cells in resected Bonora G. Costa PL. Ferri GL. Scrum hyperplasia in peptic-ulcer disease stomachs from patients with peptic ulcer gastrin in chronic rancreatitis. Am J Lancet 1974:i:583-6 disease. Scand J Gastroenterol Gasrrocnterol 1980:7 3: 33-6.

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