The patient in this question was diagnosed with Zollinger-Ellison syndrome.
One of the most important initial measures in the treatment of this condition is to control acid hypersecretion.
Proton pump inhibitors, such as omeprazole, rabeprazole, pantoprazole, and lansoprazole, are given at a dose of 40-120 mg/day and titrated to achieve a basal acid output of
In standard doses, proton pump inhibitors inhibit 90–98% of 24-hour acid secretion. Proton pump inhibitors undergo rapid first-pass and systemic hepatic metabolism and have negligible renal clearance.

Zollinger -Ellison syndrome symptoms and their frequencies
Pain (79–100%), diarrhea (30–75%), esophageal symptoms (31–56%), and flushing is not a feature of this disease.

Zollinger Ellison syndrome is a malignancy of the gastrin secreting G cells present in the antral mucosa of the stomach. Parietal cells secrete acid and intrinsic factor, chief cells secretes pepsinogen, ECL cells synthesize histamine, and secretin is synthesized by the S cells of the duodenum. 

Ans. is ‘b’ i.e., Proton pump inhibitors
“Proton pump inhibitors are the drug of choice for Zollinger Ellison syndrome; they have decreased the need for total gastrectomy”.

Ans. is ‘c’ i.e., Beta cell tumours of pancrease 

• Gastrinoma or Zollinger Ellison syndrome is a non 13 cell neuroendocrine tumour of the pancreas It secretes gastrin
• Pathophysiology of Gastrinoma

Gastrinoma —> Increase secretion of gastrin —> marked gastric acid hypersecretion peptic ulcer

Pancreatic Neuroendocrine Tumors

Ans. is ‘c’ i.e., Excision of tumour alone 

Ans. is ‘d’ i.e. Serum gastrin value of 200 pg/ml with secretin stimulation 

Diagnosis of ZES is made by secretin provocative test when serum gastrin value increases 200 pg/mL within 15 minutes [ Look closely at option (d). It says serum gastrin value of 200 pg/mL with secretin stimulation. It mentions the absolute serum gastrin level, not the increase in level]

Zollinger Ellison syndrome

• ZES is caused by gastrin secreting gut neuroendocrine tumors (gastrinomas), which result in hypergastrinemia and acid hypersecretion.
• Clinical situations that create suspicion for ZES are

– ulcers in unusual locations, ulcers in the second part of the duodenum & beyond (includes the option c) ulcers refractory to standard medical therapy

– ulcer recurrence after acid-reducing surgery.

– ulcers presenting with frank complications (bleeding, perforation, and obstruction)

– ulcers in the absence of H. pylori or NSAID ingestion.

– giant ulcers (> 2 cm)

– multiple duodenal ulcers

– ulcers associated with diarrhea

– ulcer patient with hypercalcemia or family h/o ulcers.

– ulcers with severe esophagitis.

– ulcers associated with prominent gastric folds

– ulcers with findings s/o MEN-1 (endocrinopathy, family h/o ulcers or endocrinopathy, nephrolithiasis)

Diagnosis of ZES (gastrinoma)

1)  The first step in the evaluation of a patient suspected of having ZES or gastrinoma is to obtain a fasting gastrin level.

All gastrinoma patients have a fasting gastrin level > 150 pg/mL.

2)       The next step is to assess acid secretion by measuring basal acid output (BAO) which should be 15 meq/h (normal < 4 meq/h)

[This is done to rule out hypochlorhydria which is a much more common cause of hypergastrinemia than gastrinoma]

A gastric pH of > 3.0 implies hypochlorhydria and excludes gastrinoma.

3)       Gastrin Provocative tests

– In a pt. with pH < 2.0 or BAO . 15 meq/hr and fasting gastrin level > 1000 pg/mL, the diagnosis of ZES is confirmed.

– With pH < 2.0 or BAO 15 meq/L and lower gastrin levels (150-1000 pg/mL), a secretin stimulation test is performed to distinguish ZES from other causes of hypergastrinemia. A rise of 200pg/mL of serum gastrin level within 15 min of secretin injection, confirms ZES.

Ans. is ‘b’ i.e. Exocrine tumor
Zollinger–Ellison syndrome
This syndrome is mentioned here because the gastrin-producing endocrine tumor is often found in the duodenal loop, although it also occurs in the pancreas, especially the head.
Pathophysiology-

• Hypergastrinemia originates from autonomus neoplasm.
• Gastrin stimulates acid secretion through the gastrin receptor on parietal cells.
• It is caused by a gastrin-secreting tumor. (G cells)
• It is an exocrine tumor.

• PPIs are the treatment of choice (Omeprazole)
• Recurrence may occur after surgery.

Ans. is ‘a’ i.e., Duodenum 

Answer is D (Massive HCL in response to histamine injection) :

Massive secretion of HCI is seen in response to stimulation with Secretin (not with Histamine).

Zollinger Ellison Syndrome (as mentioned in the previous question) is characterized by unregulated secretion of gastrin leading to hypersecretion of gastric acid and the resulting manifestations. The most common presentation is with :

Gastrin provocative tests are used when acid secretory studies are not contributory and include :

1. Secretin stimulation test ^Q most sensitive and specific Q

2. Calcium infusion test

3. Standard meal test

Histamine stimulation is not used and it does not bring about massive release of HCI in such patients.

Answer is A (Peptic Ulceration, Gastric Hypersecretion, Non-β Cell Tumour)

Zollinger Ellison Syndrome is characterized by peptic ulceration due to gastrin hypersecretion by a non-beta cell tumor.

Ans. B: Omeprazole

They are the most effective antisecretory medication available because they block the hydrogen potassium/adenosine triphosphate (ATPase) pump, the final common pathway, regardless of the stimulus.

The acid environment in the stomach allows for the release of the prodrug granules, which are then absorbed in the duodenum. Once in the systemic circulation, they are taken up by gastric parietal cells and diffuse into the extracellular canaliculus. The PPI then covalently and irreversibly binds to the proton pump. PPIs require acid for accumulation and activation, which is why they are most efficacious on an empty stomach.

PPIs are rapidly and almost completely absorbed. The peak plasma concentration is reached in 1-3 hours. The prodrug is quickly metabolized by the liver, primarily by cytochrome P-450 isoenzyme CYP2C19, resulting in a half-life of roughly 1 hour.

Despite the short half-life of PPIs, the irreversible covalent bonding to the proton pump provides sustained antisecretory effects; therefore, the effect is not due to plasma concentration of the drug but rather the area under the plasma concentration curve.

Ans. B i.e. Secretin simulation test

• MC site: Duodenum
• Non beta cell tumour,
• Neuro-endocrine tumour/ NET secreting: Gastrin
• Most important investigation: Secretin stimulation test
• DOC for ZES: Proton pump inhibitors
• Hepatic metastasis occurs (33%)

Ans. B: Reduced BAO : MAO ratio
Zollinger-Ellison syndrome (ZES) is a rare condition characterized by peptic ulcers that are refractory to conventional medical therapy.

Gastrin-producing tumors or gastrinomas cause excessive gastric acid secretion, leading to ulcers of the upper GI tract, as well as diarrhea and severe abdominal pain.

Laboratory studies to confirm the diagnosis of ZES include the following:

Measurements of fasting serum gastrin levels

– Gastrin levels higher than 100 pg,/mL are highly suggestive of ZES. If the gastric pH level is less than 2.5, a gastrin level of higher than 1000 pg/mL is diagnostic of ZES.

If the patient is not receiving acid-suppressing medication and the gastric pH levels are higher than 2, ZES can be ruled out.
Secretin stimulation test

After blood to measure the basal gastrin level is obtained, 2 IU/kg of secretin is intravenously administered. Blood is obtained at 2.5 minutes, 5 minutes, 10 minutes, 15 minutes, and 30 minutes.

An increase of serum gastrin levels to higher than 200 pg/mL is diagnostic of ZES.

– It is the most important diagnostic test to exclude other conditions with increased acid secretion, hypergastrinemia, or both.

–  Clinical conditions in which patients present with hypergastrinemia, such as gastric outlet obstruction, pernicious anemia, renal failure, and achlorhydria due to atrophic gastritis, must be excluded with secretin provocative testing.

Measurement of basal acid output

–  Before measurement of the basal acid output (BAO), acid-inhibitory agents must be discontinued: 24 hours for H2 receptor antagonists and 7 days for proton pump inhibitors (PPIs).

– In the 24 hours prior to the test, the patient receives antacids.

– In an unoperated stomach, a BAO of more than 15 mEq/h is diagnostic of Zollinger-Ellison syndrome. If the patient underwent gastric resection for acid reduction, a BAO of more than 10 mEq/h is diagnostic for Zollinger-Ellison syndrome.

• If the patient has multiple endocrine neoplasia type 1 (MEN-1), other laboratory abnormalities may be suggestive of Zollinger-Ellison syndrome.

– High plasma calcium levels

High parathyroid hormone (PTH) levels

–  High prolactin levels

Ans. is ‘a’ i.e., Gastrin secreting tumor
Zollinger-Ellison syndrome is caused by gastrin-secreting tumors.
These gastrinomas are most commonly found in the small intestine or pancreas.

Ans. is ‘c’ i.e., Gastrin

Zollinger Ellison syndrome ‑

• Severe peptic ulcer disease secondary to gastric acid hypersecretion due to unregulated gastrin release from a non 13 cell endocrine tumour (gastrinoma), defines the components of Zollinger Ellison syndrome.

Pathophysiology of Zollinger Ellison syndrome

• The driving force responsible for clinical manifestations of Zollinger Ellison syndrome is hypergastrinemia originating from Gastrinoma (autonomus neoplasm, non [3 cell neoplasm)
• Gastrinoma
• Hyper gastrinemia
• Hyper acidemia
• Peptic ulcer, erosive esophagitis and diarrhoea

Other important characteristic of Gastrinoma

• Over 80% of these tumours are seen in Gastrinoma triangle° (triangle formed between duodenum and pancreas) most of them are seen in the head of pancreas.
• About ²/₃‘of these tumours are malignant°.
• About one half of these tumours are multiple°.
• About one fourth of the patients have multiple endocrine neoplasia (MEN I) syndrome with tumours of parathyroid, pituitary and pancreatic islets being present.

Remember :

Most common site of gastrinoma’s is                   →     Duodenum (50-70%), (Pancreas 20-40%)

Most common hormone to be secreted                →     ACTH

besides gastrin is

Most common site of peptic ulcers produced is     →    l^s‘ part of Duodenum.

Most valuable provocative test in                        →     The Secretin injection tests. identifying patients with ZES is

Basal acid output is greater than 60% of out pu   →     BAO> MAO

induced by maximal stimulation

• The term pancreatic endocrine tumour is misnomer because these tumours can occur either almost exclusively in the pancreas or at both pancreatic and extrapancreatic sites