Antral gastrin cell hyperfunction associated with chronic pancreatitis

ABSTRAC T: Th is report describes a patient with antral gastrin cell hyperfunction who also had pancreatic pseudocy:m and partial common bile duct obstruction secondary ro ch ron ic pancreatitis. A 60-year-old female had a th ree-month h istory of wor~ening epigastric discomfort with episodes of nausea, vomiting and weigh t loss. The patient had no history of peptic ulcer d isease and no ulcers were demonstrated during diagnostic work-up. Baseline fasti ng serum gastrins were 715 and 1000 pg/ml [normal 50 to 170 pg/ml). These decreased to 515 pg/ml during an in travenous secretin test and increased up to 2155 pg/ml after a protein meal test. The patient also had chronic pancreatitis. multiple pancreatic pseudocysts and a partial common bile duct obstruction. Tru ncal vagotomy and antrectomy for antral gastrin cell hyperfunction. Roux-en-Y cyscjejunostomy for pancreatic pseudocysts and choledochojejunostomy for common bile duct stricture were performed. Three mon ths after the operation. the patient was symptom-free and fasting serum gastrin levels at one week, two months and three months after the surgery were ll, 40 and 50 pg/ml, respectively. Ca n J Gasti:oente rol 1988;2(3):123-1 26.

Since the volume density of antral G cells has been found to be both increased (2,5.7) a nd norma l (8), and since an increased G cell density can occur in other conditions (9-1 l ). the term an tral gastrin cell hyperfu nction appears to be most appropriate ( 12).
The incidence of thi s e nt ity is unknown, b u t with refinements of diagnos• tic procedures, includ ing serum gastri n response to protein meal and in travenous secretin.its recognition is increasi ng as awareness of its possibiliry is appreciated.T he clinical significance of differentiating between various causes o f hypergas-trincmia is obvious because their managements arc quite different.The clinical associations of antral gastrin ce ll hyperfunction include basal hypcrgastrinemia, an exaggerated gasrrin response to a protein meal.peptic ulcer disease and the absence of gastrinoma.The purpose of chis report is to presen t a patient with antral gastrin cell hyperfunction without peptic ulcer disease who also had pancreatic pseudocysts and a pa rtial common bile duct obstruction secondary co chronic pancreacitis of unknown etiology.

CASE PRESENTATION
In May 1987, a 60-year-old white female was admitted to hospi tal after the sudden onse t of acute, sharp, scabbing mid-epigastric pain.She had previously been completely asymptomatic and the present complaints had developed fo llowing a heavy meal.The patient was diagnosed as having acu te pancreatitis and medical management was begun.Because of epigastric discomfort, esophagogastrod uodenoscopy was performed.A 'beefy appearing gastric mucosa wit', edematous folds' was described.There was no ulcer or gastric oudet obstruction.Gastric aspirate p H was 1.0 by indicator paper and fasting serum gastri n concentration was 1800 pg/mL.An abdom inal computerized tomography (CT) scan showed a mass in the tail of the pancreas.Seven days after admission symptoms had resolved and the patient was discha rged on cimetidine 800 mg bid and antacids.A follow-up serum gascrin concentration two weeks later was above 1000 pg/ml and repeat abdominal CT scan showed persistence of the previously noted pancreatic mass.The patient was referred co Tulane University Medical Center where she was admitted on August 13, 1987 fo r furt her study and treatment.
At the time of admission che patient described post prandial epigascric d istress associated with a 30 lb weigh t loss over the previous three months even though there had been no change in he r usual good appetite.There was no vomiting or diarrhea and no history of peptic ulcer d isease or pancreatic disease.She also denied alcohol and tobacco use and drug abuse.There was no fami ly history of 124 peptic ulcer disease or endocrinopathy.Physical examination was unremarkable except for mid-epigastric tenderness to palpation.
The fo llowing laborator y data were reported on admission: hemoglobin 14. l gl 100 ml, hematocrit 41.3%.white blood cell cou nt 5600/mml with normal differential, urinalysis normal, stool exam negative for occult blood and negative Sudan-Ill reaction.Blood urea nitrogen, total serum protein, albumin, liver enzymes, alkaline phosphatase, bilirubin, electrolytes, calcium concen trations and lipid profile in scrum, serum and urinary amylase concentrations were within normal limits.
Stimulation tests for sc rum gastrin were perform ed by th e intravenous administration of secreti n 2 U/kg (Pharmacia, Inc) and by administration of a protein meal.Fasting venous blood samples were taken through an intravenous catheter 15 and 5 mins before secretin injection and then 1, 2, 5, 10, 15, 30 and 60 m ins after the injection.
Immediately after completion of the secrctin test, the patient ate a test meal consisting of three eggs, two slices of bacon, two slices of toast and 8 oz of milk containing 2% butterfat.The meal contained 34.5 g protein, 26.6 g fat and 4 Ll g carbohydrate ( 5).Blood samples were taken 0, 5, 10, 15, 30 and 60 m ins after starting the meal.Serum gastri n was measured in all blood samples using a radioimmunoassay technique which speci fically measures physiologically active gastrin, both G-17 and G-34 (13).Ele-vatcd baseline seru m gastrin concentrations (715 and 1000 pg/mL) decreased (down to 515 pg/ml) after intravenous secretin ; there was an exaggerated increase (up to 2155 pg/ml) after the protein meal (Figure I ).Serum concentrations of prolactin ( l l.2 pg/ml), pancreatic polypeptide (253 pg/ml) and parathyroid hormone (25 µl Eq/ml) were withi n normal limits.
Because of the low p H value of gastric aspirate during the initial esophagogastroduodcnoscopy and the patient's significan t epigastric discomfort, a gastric secretory srudy was deferred.However, the scrum grou p I pepsinogen concentration was 200 ng/ml (normal, 25 to lOO ng/ml) and was consistent with i n creascd gastric secretory capacity.Endoscopic retrograde cholangiopancreatography (ERCP) showed a partial obstruction of the intrapancrcatic portion of the distal common bile duct.Also noted were dilatation of the proximal common bile duct (approximately 21 mm in diameter) a nd intrahepatic bile ducts (Figu re 2).The main pancreatic duct was diffusely narrowed and wa~ more prominent in the body and the tail.Contrast extravasation during ERCP was interpreted as representing a pseudocyst in che tail of the pancreas.
Because of th e patient's persistent symptoms, surgical exploration was performed on August 17.1987.No intraabdominal gastrinoma was found.The pancreas was noted co be firm and appeared chronically inflamed.T here were two pscudocysts in the body and plasia.The present patient had not had a p rior vagotomy to account for this.The auth ors believe that the patient had antral gastrin cell hypcrfunction with a fasting hypergastrinemia and an exaggerated gastrin response to a protein meal.Moreover, the dramatic return of hypcrgastrincmia to normal after antrectomy and vagoromy suggested that the ant rum was the sole ~ource of the excess scrum gastrin .
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 mcruliepacic hile cl11cr., The main Jnrncreuric duce tl'as dijf11sel:, nmroH'ed This is the first reported ca~e o( antral gasrrin cell hyperfunction associated with chronic pancreatitis and its complicarions, such as p:mcrcmic pscudocyscs and a partial common hile duct obstruction .Fasting and postprandial hypcrgastrincmia have been ohserved in patients with chronic pancrcatitis ( 14, I 5).This hypcrgastrincmia may be secondary to chronirnll y reduced gastric acid secretion ( 14).On the other hand, a more recent study indicated that patients with severe pancrcmic insufficiency frequently have had gawic acid hypcrsccretion ( 15).However, none of the previous studies showed basal gastrincmia above 400 pg/ml in these raticnts ( 14.16).This association appears co be coincidental in the present case.Despite significant partial strictun: of the disrnl common bile duct combined with di latation of extra-and intrahepatic bile ducts, the patient's liver function tests were within normal limits.
tail The following procedures were pcrtormcd: pancreatic biopsy; Roux-cn -Y pancrcaricocyscjej u nostomy; cholecystectom y: Roux-en-Y choledochojeiunostomy.and antrcctomy and vagotomy.Pathologic exam of the pancreatic biopsy \\'as consistent with chronic p:rncreacitis.The gastric ancrum showed chronic hypertrophic gastritis.pancreatic acinartype and intestinal metaplasia with G cell hypcrplasi;i .The gallhladder showed chronic cholecystills with cholesterolosis.The patient's postorcrntive course wa, uneven tf u I.The pntieni was discharged on August 26.1987 and h:is remained well for at least the last five months and i now on pancremic cn:ymc therapy and has gained 20 lbs.Fasting scrum gasrrin levels at the end of the first postoperative week.two months and three months after surgery were 11.40 and 50 pg/ml.respectively.

DISCUSSION
Zollinger-Ellison syndrome has been classified into two types; type 1, due to antral gastrin cell hypcrfunction and type 2, due co a gastrinoma (I).Characteristically.antral gasrrin cell hyperfunction patients have been mostly male, rcbtivcly young (oldest 58 years old) and have always had peptic ulcer disease with acid hypcrsecretion.moderate fasting hypc rgastrincmia with an exaggerated n.:sponse to ,1 standard rest meal and a minimal gastrin response to intravenous sccrccin ( 1-8 ).Some of the patients in chc original study ( l ). as well as chose reporccd hy other authors (4. 5 ), had pre-This is the oldest patient reported with antral gastrin cel l hyperfunction ( 1-8, l2).

ERTAN er al
Although the previously reported patients had a strong family history of peptic ulcer disease among first degree relatives and had a form of peptic ulcer chat was recurren t and resistant to medical management, the present patient had neither previous nor present peptic ulcer disease nor a family history of ulcer disease.One ocher antral gascrin cell hyper-ACKNOWLEDGEMENTS:  (5).Antra l gastrin cel l hyperfunction might result from abnormal or excessive trophic factors, excessive neurogenic stimulation or an inappropriate physiologic response.Although the pathogenesis of primary G cell hyperp lasia remai ns co be e lucidated, the response of