Pancreatic exocrine insufficiency: diagnostic evaluation and replacement therapy with pancreatic enzymes

In chronic pancreatitis over a course of years to decades, pancreatic parenchyma is gradually lost and pain is gradually decreasing as signs and symptoms of malabsorption appear. Appearance of calcifications is a late sign and in many cases coincides with appearance of steatorrhea. Decreasing output of insulin and glucagon results in diabetes mellitus, which is characterized by a high risk of hypoglycemias ('brittle' diabetes). In most instances, measurement of fecal concentration of elastase may be sufficient to diagnose exocrine pancreatic insufficiency. Fecal fat analysis is useful to establish malabsorption and to monitor pancreatic enzyme replacement therapy. Components essential to the optimal management of chronic pancreatitis are control of pain, improvement of maldigestion, management of diabetes and of complications like cysts or strictures, and alcohol and nicotine abstinence. Patients with pain are evaluated for structural abnormalities which can be treated endoscopically or surgically. Conservative treatment of pain includes fat-reduced diet, nonnarcotic analgesics, alcohol and smoking cessation, and, if not successful, an 8-week trial of high-dose pancreatic enzymes. Pancreatic enzymes are used for the treatment of maldigestion. Digestion of fat is the determining factor in pancreatic insufficiency. Treatment success is defined clinically by improved body weight and consistency of feces. Modern pancreatin preparations are engineered as acid-resistant, pH-sensitive microspheres. Using such preparations, most patients will reduce their steatorrhea to <15 g fat per day during supplementation of 25,000-40,000 IU of lipase per meal, but in selected cases larger doses may be needed, depending on size of the meal and severity of the disease. Efficacy of enzyme replacement therapy is influenced by denaturation of lipase by gastric acid, improper timing of enzymes, coexisting small-intestinal mucosal disease, rapid intestinal transit and effects of diabetes. This review focuses on pathophysiology, diagnosis and treatment of pancreatic steatorrhea.