Hospital Medicine

Pancreatic Insufficiency

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I. What every physician needs to know.

Pancreatic insufficiency mainly refers to decrease in exocrine function of the pancreas when there is insufficient delivery of the pancreatic digestive enzymes to the small intestine for adequate digestion of the ingested food. It is thus a significant cause of malabsorption.

II. Diagnostic Confirmation: Are you sure your patient has Pancreatic Insufficiency?

There are no set criteria established by any society to confirm diagnosis of pancreatic insufficiency. Detailed history gives clue to the diagnosis. Patient often has symptoms suggestive of chronic pancreatitis and develops steatorrhea suggesting deficiency of pancreatic enzymes.

The simple way to diagnose pancreatic insufficiency is to see if there is significant improvement in symptoms with trial of pancreatic enzymes.

A. History Part I: Pattern Recognition:

The typical patient mostly has a history of underlying chronic pancreatitis. Patients with mild enzyme insufficiency generally have no clinical symptoms and have normal bowel movements. Steatorrhea with foul-smelling, high volume fatty stools and chronic abdominal pain and bloating sensation occurs due to fat malabsorption when more than 90% of the enzyme secretion is compromised.

Also these patients develop deficiencies of fat soluble vitamins (A, D, E and K), magnesium, calcium, zinc and folic acid. These nutrient deficiencies rarely result in symptoms such as tetany, glossitis, peripheral neuropathy and osteoporosis. There is increased risk of cardiovascular events due to loss of protective lipoproteins against atherogenesis.

B. History Part 2: Prevalence:

Pancreatic insufficiency can develop due to:

1. Parenchymal loss - most commonly chronic pancreatitis but can also happen due to severe acute pancreatitis, pancreatectomy and inherited conditions like cystic fibrosis and shwachman-diamond syndrome.

2. Pancreatic duct obstruction-- strictures, stones, malignancy.

3. Asynchrony between gastric emptying and enzyme secretion - diabetes mellitus, Crohns disease, short bowel syndrome.

The cause of chronic pancreatitis may affect the progression to development of pancreatic insufficiency - in autoimmune pancreatitis, insufficiency is seen very commonly (more than 75% at presentation), alcoholic patients develop insufficiency after about 10 years and idiopathic CP take up to 20 years to develop pancreatic insufficiency.

C. History Part 3: Competing diagnoses that can mimic Pancreatic Insufficiency.

Celiac disease, childhood history of ill health, and a positive family history of gluten sensitivity or Crohn's disease.

D. Physical Examination Findings.

The exam findings are related to the deficiency of calories and nutrients due to malabsorption. They can have weight loss with normal appetite.

Severe Vitamin D and calcium deficiency can result in signs of hypocalcemia like tetany, Trousseau and Chvostek sign.

Vitamin A deficiency can result in follicular hyperkeratosis and night blindness.

Vitamin K deficiency can cause bleeding disorders and spontaneous hematomas.

E. What diagnostic tests should be performed?

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Invasive or direct testing

This is sensitive for diagnosis of even mild chronic pancreatitis and enzyme insufficiency but lack standardization. It is cumbersome, restricted to few medical centers and thus not commonly used in clinical practice.

Basically, the pancreas are stimulated either directly by hormones (secretin or cholecystokinin) or indirectly using a Lund test meal followed by direct collection of pancreatic juices from duodenum and measurement of pancreatic enzymes and bicarbonate levels in the pancreatic secretions.

Non-invasive testing

This is not perfect but much easier to do and commonly used in clinical practice. They are useful to diagnose advanced pancreatic insufficiency and not sensitive for mild insufficiency.

Fecal tests:Qualitative evaluation of fat in stool using Sudan stain is nonspecific and of no value. Quantitative evaluation of fecal fat is gold standard for steatorrhea diagnosis but is very cumbersome - involves72 hours collection of stools from a patient on fixed diet of about 100 gm fat/day and discontinuation of enzyme replacement for a week prior to the test. Excretion of more than 7 gm/day of fat is diagnostic of fat malabsorption.

Fecal elastase test is most commonly used to detect insufficiency and measures human elastase-1 in stool (normal > 200 μg/g). This can be done on a single sample of stool without discontinuation of enzyme replacement. It is highly sensitive (100%) for severe disease but sensitivity decreases for mild (0-63%) to moderate (77-100%) disease. The specificity is 93% but can be compromised in patients with small intestinal diseases like Crohn's disease, short gut syndrome etc.

Fecal chymotrypsin test is less sensitive and specific than elastase test and needs discontinuation of enzymes for 2 days before the test.

Blood tests:Serum trypsinogen is a cheap and easy laboratory test with levels <20 ng/ml being sensitive and specific for advanced pancreatic enzyme insufficiency.

Breath tests: The13C-MTG test involves oral intake of13C- marked substrates and measures the13CO2in breath sample which would give an idea of proportion of food absorbed in the intestine and ultimately released across pulmonary endothelium. This test has sensitivity of 89% and specificity of 81%. It is sensitive in detecting mild to moderate insufficiency and can help in determining efficacy of enzyme replacement therapy.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Changes of advanced chronic pancreatitis may be evident on imaging done in patients with severe pancreatic insufficiency.

Thus, KUB may show pancreatic calcifications in approximately 30% of patients especially in alcoholic pancreatitis. Similarly ultrasound, computed tomography (CT) scans and magnetic resonance imaging (MRI) may show calcifications and abnormalities in pancreatic morphology.

Recently secretin-enhanced MRCP is being researched for evaluation of pancreatic exocrine function and for early diagnosis of pancreatitis. Secretin stimulation may improve the visualization of pancreatic duct anatomy on MRI but it is an expensive test and its value in routine clinical practice is still not established.

ERCP and endoscopic ultrasound (EUS) may help in diagnosis of early pancreatitis not yet visible on conventional imaging but both are invasive tests with associated complications.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

III. Default Management.

The goals of treatment are:

1. Prevent further weight loss and return towards ideal body weight.

2. Control of symptoms like steatorrhea, bloating, abdominal pain.

3. Correction of vitamin deficiencies.

Depending on the nutritional status, steatorrhea symptoms can be controlled by restricting the fat content of the diet to less than 20 gm fat/day but most of the patients should rather be treated with enzyme supplementation for control of symptoms and improvement of their nutritional status.

The enzyme requirement depends on person's weight, severity of enzyme deficiency and fat content of the meal. A good starting dose is 500 units/kg/meal and adjust the dose according to symptoms and stool fat content. Most patients require doses ranging from 25,000 to 75,000 units of lipase for a meal and 10000 to 25000 units for snacks. One half of the dose should be taken with the first bite of the meal and remaining half midway between the meal to allow proper mixing of the enzymes with the food.

Vitamin D supplementation should be considered in these patients due to malabsorption of fat soluble vitamins. The response should be monitored by measuring serum calcium levels in a few weeks as there is a possibility of developing hypercalcemia due to overdosing of vitamin D.

A. Immediate management.

B. Physical Examination Tips to Guide Management.

1. Monitor weight.

2. Monitor symptoms, including steatorrhea, abdominal pain, etc.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Monitor Vitamin D and calcium levels every 2-3 weeks till stable doses established.

Monitor uric acid levels - as these enzymes are purine based.

Monitor sugar levels as they can cause worsening of diabetes mellitus.

D. Long-term management.

E. Common Pitfalls and Side-Effects of Management.

Most common side effects include headache and abdominal discomfort. Other symptoms include nausea, bloating sensation, hypersensitivity.

Fibrosing colonopathy progressing to colonic stricture has been reported in children using very high doses of enzymes over a long period of time but this complication is not seen under the maximum doses mentioned above.

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

Contain purines which may increase uric acid concentration. No change in dose recommended.

B. Liver Insufficiency.

No change in standard management.

C. Systolic and Diastolic Heart Failure.

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No change in standard management.

E. Diabetes or other Endocrine issues.

Calorie absorption may improve with initiation of pancreatic enzymes. Theoretically that may lead to increased insulin requirement for metabolism of the increased calories.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

This is the treatment for pancreatic insufficiency.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

No change in standard management.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

If the patient's symptoms do not improve - the dosing can be increased.

If the underlying cause is alcoholism and the patient is still actively drinking - there is risk of withdrawal while being in hospital, should monitor for any withdrawal symptoms in that case.

B. Anticipated Length of Stay.

Pancreatic insufficiency is mainly managed as an outpatient with pancreatic enzymes. If decided to do inpatient workup to confirm the diagnosis, the patient may be in hospital for 2-3 days getting the tests mentioned above.

C. When is the Patient Ready for Discharge.

The patient can be discharged if he is able to tolerate the oral pancreatic enzymes and oral diet and if he is not significantly dehydrated or weak due to the steatorrhea.

Also if the patient has significant pain issues due to the chronic pancreatitis, he may need a good oral regimen for pain control before discharge.

D. Arranging for Clinic Follow-up.

Close followup needed to see effect of pancreatic enzymes on patient symptoms and to titrate the dosage as needed.

1. When should clinic follow up be arranged and with whom.

Should follow with Gastroenterology or Pancreas clinic (if available) in 2-3 weeks after discharge.

May need follow up with pain clinic for management of chronic pancreatitis pain.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

Basic labs: CBC, BMP (mainly calcium levels), vitamin D levels, INR at baseline and can follow these labs to see improvement with pancreatic enzymes.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Follow up on the tests mentioned above and look for improvement with pancreatic enzymes.

E. Placement Considerations.

If the patient is significantly malnourished to the point that he is not able to do his activities of daily living and not enough support at home, he may need placement in skilled facility till his nutritional status and activity level improves.

For patients not able to tolerate any enteral nutrition, consideration may be needed for parenteral nutrition which may need PICC line or a tunneled catheter placement by interventional radiology.

F. Prognosis and Patient Counseling.

The prognosis is generally good with compliance of pancreatic enzymes supplementation with the meals.

Patients need counselling and education about the right way to take enzymes and titration of doses according to symptoms.

If still drinking alcohol, strong counselling for quitting alcohol.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Counsel patients about the most common causes and adjustments to be made for treatment failure as below:

  1. Check patient compliance and patient comprehension of the best way to take the medications. Patients benefit by close follow up with nutritionist.

  2. Can increase lipase dose up to a maximum of 10,000 units/kg/day but most adult patients do not need such high doses.

  3. Consider inhibition of gastric secretion by proton pump inhibitors.

  4. Rule out other diseases such as celiac disease, bacterial overgrowth syndrome.

  5. Decrease fat content in diet.

VII. What's the evidence?

Dominguez-Munoz, JE. "Pancreatic enzyme therapy for pancreatic exocrine insufficiency". Gastroenterol Hepatol (N Y). vol. 7. 2011. pp. 401-403.

Dominguez-Munoz, JE. "Pancreatic exocrine insufficiency: Diagnosis and treatment". J Gastroenterol Hepatol 26 Suppl. vol. 2. 2011. pp. 12-16.

Sikkens, EC, Cahen, DL, Kuipers, EJ, Bruno, MJ. "Pancreatic enzyme replacement therapy in chronic pancreatitis". Best Pract Res Clin Gastroenterol. vol. 24. 2010. pp. 337-347.

Stevens, T, & Parsi, MA. "Update on endoscopic pancreatic function testing". World J Gastroenterol. vol. 17. 2011. pp. 3957-3961.

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