Zollinger- Ellison Syndrome

ZOLLINGER- ELLISON SYNDROME

Q. 1

A patient is diagnosed with Zollinger-Ellison syndrome. Which of the following would be the most appropriate pharmacotherapy?

 A

Erythropoietin

 B

Famotidine

 C

Fluorouracil

 D

Omeprazole

Q. 1

A patient is diagnosed with Zollinger-Ellison syndrome. Which of the following would be the most appropriate pharmacotherapy?

 A

Erythropoietin

 B

Famotidine

 C

Fluorouracil

 D

Omeprazole

Ans. D

Explanation:

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 the 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.

Also know:

Erythropoietin is a glycoprotein, normally produced in the kidneys, that stimulates stem cells to differentiate into rubriblasts, increases the rate of mitosis, increases the release of reticulocytes from the bone marrow and increases hemoglobin (Hgb) formation. EPO is indicated for the treatment of anemia associated with chronic renal failure, zidovudine therapy, chemotherapy, and for reduction of allogeneic blood transfusions in surgery patients.

Famotidine is an H2-antagonist that decreases gastric acid secretion by competitively and reversibly inhibiting histamine receptors on parietal cells. Although famotidine could potentially be used in the treatment of Zollinger-Ellison syndrome, a proton pump inhibitor is a more appropriate treatment measure.

Fluorouracil or 5-FU, is an example of an antimetabolite that blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. This results in interference with DNA synthesis, and to a lesser extent, RNA synthesis. 5-FU is indicated for the palliative management of colon rectum, breast, stomach and pancreatic carcinoma.
 
Ref: McQuaid K.R. (2012). Chapter 62. Drugs Used in the Treatment of Gastrointestinal Diseases. In B.G. Katzung, S.B. Masters, A.J. Trevor (Eds),Basic & Clinical Pharmacology, 12e.

Q. 2

Zollinger Ellison Syndrome is diagnosed if serum gastrin level is greater than:

 A

100 pg/ml

 B

500 pg/ml

 C

1000 pg/ml

 D

5000 pg/ml

Q. 2

Zollinger Ellison Syndrome is diagnosed if serum gastrin level is greater than:

 A

100 pg/ml

 B

500 pg/ml

 C

1000 pg/ml

 D

5000 pg/ml

Ans. C

Explanation:

The diagnosis of ZES is made by measuring the serum gastrin level. It is important that patients stop taking proton pump inhibitors for this test.

In most patients with gastrinomas, the level is >1000 pg/mL. Gastrin levels can be elevated in conditions other than ZES.

Common causes of hypergastrinemia include pernicious anemia, treatment with proton pump inhibitors, renal failure, G-cell hyperplasia, atrophic gastritis, retained or excluded antrum, and gastric outlet obstruction.

In equivocal cases, when the gastrin level is not markedly elevated, a secretin stimulation test is helpful. 
 
Ref: Schwartz’s principle of surgery 9th edition, chapter 33.

Q. 3

Most common presenting symptom of Zollinger -Ellison syndrome is:

 A

Diarrhea

 B

Pain

 C

Esophageal symptoms

 D

Flushing

Q. 3

Most common presenting symptom of Zollinger -Ellison syndrome is:

 A

Diarrhea

 B

Pain

 C

Esophageal symptoms

 D

Flushing

Ans. B

Explanation:

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.

 

Ref: Harrisons principles of internal medicine, 18th edition, Page: 3057

Quiz In Between


Q. 4

Tumor of which of the following type of cells result in Zollinger Ellison syndrome?

 A

ECL cells

 B

Chief cells

 C

G cells

 D

S cells

Q. 4

Tumor of which of the following type of cells result in Zollinger Ellison syndrome?

 A

ECL cells

 B

Chief cells

 C

G cells

 D

S cells

Ans. C

Explanation:

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. 

Ref: LANGE’S Gastrointestinal Physiology By Kim E Barrett chapter 3.

Q. 5

Drug of choice for Zollinger-Ellison syndrome

 A

Antihistaminics

 B

Proton pump inhibitors

 C

Dopamine agonists

 D

Antacids

Q. 5

Drug of choice for Zollinger-Ellison syndrome

 A

Antihistaminics

 B

Proton pump inhibitors

 C

Dopamine agonists

 D

Antacids

Ans. B

Explanation:

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”.


Q. 6

All of the following are features of Zollinger Ellison syndrome except

 A

Intractable peptic ulcers

 B

Severe diarrhoea

 C

Beta cell tumors of the pancreas

 D

Very high acid output.

Q. 6

All of the following are features of Zollinger Ellison syndrome except

 A

Intractable peptic ulcers

 B

Severe diarrhoea

 C

Beta cell tumors of the pancreas

 D

Very high acid output.

Ans. C

Explanation:

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

Tumour

Biologically active

peptide secreted

Tumour location

Malignant

percentage

Main symptoms and signs

Gastrinoma

(non 13 cell

tumour)

Gastrin

Duodenum (70%)

Pancreas (25%)

other sites (5%)

60-90

•Pain              (79 100%)

‘Diarrhoea (30 73%)

•   GERD        (30-35%)

•   Peptic ulcer

Insulinoma

(f3 cell tumour)

Insulin

Pancreas > 99%

(Insulinomas are

distributed equally on

head body and tail of

pancrease)

< 10

•   Symptoms of hypoglycemia

•   Symptoms releive on

administration of glucose

VIPOMA

(Verner-

Morrison

syndrome,

pancreatic

cholera,

WDHA)

Vasoactive

intestinal

peptide

Pancreas 90%

40-70

•   Watery diarrhoea

(90-100%)

•                          –

Hypokalemia (80 100%)

•   Hypochlorhydria

•   Dehydration (83%)

•   Flushing (20%)

Glucagonoma

Glucagon

Pancreas 100%

(usually

occursusuall

singly in

pancreatic tail)

50-80%

•   Dermatitis (migratory

necrolytic erythema)

67-90%

•   Glucose intolerance

(40-90%)

•   Weight loss (66 to 96%)

•   Anemia (33-85%)

•   Diarrhoea (15-29%)

•   Thromboembolism

Quiz In Between


Q. 7

Treatment of Zollinger Ellison syndrome –

 A

Total gastrectomy with removal of tumour

 B

Partial gastrectomy

 C

Excision of tumour alone

 D

HZreceptor antogonist

Q. 7

Treatment of Zollinger Ellison syndrome –

 A

Total gastrectomy with removal of tumour

 B

Partial gastrectomy

 C

Excision of tumour alone

 D

HZreceptor antogonist

Ans. C

Explanation:

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


Q. 8

A 45-year-old gentleman has undergone truncal vagotomy and pyloroplasty for bleeding duodenal ulcer seven years ago. Now he has intractable recurrent symptoms of peptic ulcer. All of the following suggest the diagnosis of Zollinger Ellison syndrome, except:

 A

Basal acid output of 15 meq/hour

 B

Serum gastrin value of 500 pg/ml

 C

Ulcers in proximal jejunum and lower end of esophagus

 D

Serum gastrin value of 200 pg/ml with secretin stimulation

Q. 8

A 45-year-old gentleman has undergone truncal vagotomy and pyloroplasty for bleeding duodenal ulcer seven years ago. Now he has intractable recurrent symptoms of peptic ulcer. All of the following suggest the diagnosis of Zollinger Ellison syndrome, except:

 A

Basal acid output of 15 meq/hour

 B

Serum gastrin value of 500 pg/ml

 C

Ulcers in proximal jejunum and lower end of esophagus

 D

Serum gastrin value of 200 pg/ml with secretin stimulation

Ans. D

Explanation:

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 the 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 second part of duodenum & beyond (includes the option c) ulcers refractory to standard medical therapy

– ulcer recurrance 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 diarrhoea

– 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 evaluation of a patient suspected of having ZES or gastrinoma is to obtain as 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 Z 15 meq/h (normal < 4 meq/h)

[This is done to rule out hypochlorhydria which is 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 perforfmed 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.



Q. 9

Zollinger Ellison syndrome true about A/E:

 A

Surgery is to be done

 B

Exocrine tumor

 C

Endocrine disorder

 D

Secretory diarrhea seen

Q. 9

Zollinger Ellison syndrome true about A/E:

 A

Surgery is to be done

 B

Exocrine tumor

 C

Endocrine disorder

 D

Secretory diarrhea seen

Ans. B

Explanation:

Ans. is ‘b’ i.e. Exocrine tumor

Quiz In Between


Q. 10

Which of the following organs is the most common site of origin of the tumour associated with the Zollinger-Ellison syndrome –

 A

Duodenum

 B

Lymph nodes

 C

Spleen

 D

Pancreas

Q. 10

Which of the following organs is the most common site of origin of the tumour associated with the Zollinger-Ellison syndrome –

 A

Duodenum

 B

Lymph nodes

 C

Spleen

 D

Pancreas

Ans. A

Explanation:

Ans. is ‘a’ i.e., Duodenum 


Q. 11

Zollinger-Ellison syndrome is characterized by all of the followingexcept

 A

Post bulbar ulcer

 B

Recurrent duodenal ulcer

 C

Severe diarrhea

 D

Massive HCL in response to histamine injection

Q. 11

Zollinger-Ellison syndrome is characterized by all of the followingexcept

 A

Post bulbar ulcer

 B

Recurrent duodenal ulcer

 C

Severe diarrhea

 D

Massive HCL in response to histamine injection

Ans. D

Explanation:

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 :

Peptic ulceration Q

:

 

•    Most common manifestation, occuring in 90% of patient

 

 

•        Most common site is duodenum (duodenal bulb)

 

 

•        Clinical situations that raise special suspicion include :

 

 

a. Ulcers beyond the duodenal bulb (second part of duodenum and beyond) because these are unusual locations for ulcers in Peptic ulcer diseases.Q

b. Ulcers refractory to standard medical therapy Q

c. Ulcers are recurrentQ

d. Ulcers presenting with frank complications.Q

Diarrhea Q :

 

Is the most common manifestation Q

 

 

Etiology is multi factorial, and it may have a secretory component as well.

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.


Q. 12

. The triad originally described by Zollinger Ellison syndrome is characterized by

 A

Peptic ulceration, gastric hypersecretion, non beta cell tumour

 B

Peptic ulceration, gastric hypersecretion, beta cell tumour

 C

Peptic ulceration, achlorhydria, non beta cell tumour

 D

Peptic ulceration, achlorhydria, beta cell tumour

Q. 12

. The triad originally described by Zollinger Ellison syndrome is characterized by

 A

Peptic ulceration, gastric hypersecretion, non beta cell tumour

 B

Peptic ulceration, gastric hypersecretion, beta cell tumour

 C

Peptic ulceration, achlorhydria, non beta cell tumour

 D

Peptic ulceration, achlorhydria, beta cell tumour

Ans. A

Explanation:

Answer is A (Peptic Ulceration, Gastric Hypersecretion, Non (3 Cell Tumour)

Zollinger Ellison Syndrome is characterised by peptic ulceration due to gastrin hyper secretion by a non beta cell tumor.

Quiz In Between


Q. 13

Treatment for Zollinger-ellison syndrome is:

September 2005

 A

Cimetidine

 B

Omeprazole

 C

Misoprostol

 D

aluminium hydroxide

Q. 13

Treatment for Zollinger-ellison syndrome is:

September 2005

 A

Cimetidine

 B

Omeprazole

 C

Misoprostol

 D

aluminium hydroxide

Ans. B

Explanation:

Ans. B: Omeprazole

Proton pump inhibitors have become the first-line treatment in Zollinger-Ellison syndrome.

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.


Q. 14

Most important investigation for diagnosis of Zollinger Ellison syndrome is:       

March 2013

 A

Ca2+ infusion test

 B

Secretin injection test

 C

ACTH stimulation test

 D

Steroid assay

Q. 14

Most important investigation for diagnosis of Zollinger Ellison syndrome is:       

March 2013

 A

Ca2+ infusion test

 B

Secretin injection test

 C

ACTH stimulation test

 D

Steroid assay

Ans. B

Explanation:

Ans. B i.e. Secretin injection test

Gastrinoma/ ZES

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

Q. 15

Which of the following is not true for Zollinger­Ellison syndrome:           

September 2008

 A

Recurrence after operation

 B

Reduced BAO : MAO ratio

 C

Gastrin producing tumour

 D

Diarrhoea may be a presenting feature

Q. 15

Which of the following is not true for Zollinger­Ellison syndrome:           

September 2008

 A

Recurrence after operation

 B

Reduced BAO : MAO ratio

 C

Gastrin producing tumour

 D

Diarrhoea may be a presenting feature

Ans. B

Explanation:

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

Quiz In Between


Q. 16

Zollinger Ellison syndrome is caused by ‑

 A

Gastrin secreting tumor

 B

Somatostatin secreting tumor

 C

CCK secreting tumor

 D

Adrenalin secreting tumor

Q. 16

Zollinger Ellison syndrome is caused by ‑

 A

Gastrin secreting tumor

 B

Somatostatin secreting tumor

 C

CCK secreting tumor

 D

Adrenalin secreting tumor

Ans. A

Explanation:

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.


Q. 17

In Zollinger Ellison syndrome what is raised‑

 A

Insulin

 B

VIP

 C

Gastrin

 D

Glucagon

Q. 17

In Zollinger Ellison syndrome what is raised‑

 A

Insulin

 B

VIP

 C

Gastrin

 D

Glucagon

Ans. C

Explanation:

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

  • o 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.
  • o About 2/3‘of these tumours are malignant°.
  • o About one half of these tumours are multiple°.
  • o 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 → ls‘ 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

Quiz In Between



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