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Exocrine pancreatic insufficiency

Tyler Stevens, MD
Darwin L Conwell, MD, MS
Section Editor
David C Whitcomb, MD, PhD
Deputy Editor
Shilpa Grover, MD, MPH


Exocrine pancreatic insufficiency is an under recognized complication of pancreatic disease [1-3]. While patients with advanced exocrine pancreatic insufficiency usually present with abdominal pain and steatorrhea, those with less severe insufficiency may only have mild symptoms. This topic will review the etiology, clinical manifestations, diagnosis, and management of exocrine pancreatic insufficiency. An overview of nutrient absorption, malabsorption, and the evaluation and management of exocrine pancreatic insufficiency in cystic fibrosis are discussed in detail separately. (See "Clinical features and diagnosis of malabsorption" and "Mechanisms of nutrient absorption and malabsorption" and "Overview of the treatment of malabsorption" and "Cystic fibrosis: Assessment and management of pancreatic insufficiency" and "Cystic fibrosis: Overview of gastrointestinal disease".)


The pancreas secretes approximately 1.5 liters of enzyme-rich fluid every day for the digestion of fats, starch, and protein. Normal pancreatic juice is clear, colorless, isotonic, and alkaline. The composition of pancreatic juice differs in basal and stimulated phases. In the fasting state, pancreatic fluid is protein-rich and has a bicarbonate concentration of 80 mEq/L. Stimulation of the pancreas after a meal increases the flow of water and the bicarbonate concentration of pancreatic juice. A large volume of alkaline, enzyme-rich fluid enters the duodenum to neutralize gastric chyme for optimal digestion.

Pancreatic secretion is controlled by hormonal and neuronal mechanisms. The principal regulatory hormones are secretin and cholecystokinin (CCK). Both are tightly regulated by negative feedback mechanisms. Secretin is released from the duodenal mucosa in response to the presence of acid in the duodenum (figure 1). Secretin primarily stimulates the release of bicarbonate and water from the interlobular duct cells and causes a gradual rise in the flow of pancreatic fluid through the ducts and a typical pattern of electrolyte secretion (figure 2). As bicarbonate concentration rises to a peak concentration of 120 mEq/L, chloride concentration decreases reciprocally to maintain isotonicity. CCK is released from gut endocrine cells in response to the entry of fat and protein into the proximal intestine (figure 3). CCK acts directly and through vagal afferents to stimulate pancreatic acinar cells to release digestive proenzymes. (See "Mechanisms of nutrient absorption and malabsorption", section on 'Fat absorption' and "Physiology of cholecystokinin" and "Secretin".)


Several conditions are associated with exocrine pancreatic insufficiency.

Chronic pancreatitis — Chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency in adults. Progressive inflammatory changes in the pancreas in chronic pancreatitis results in permanent structural damage, which can lead to impairment in exocrine function of pancreatic duct and acinar cells. (See "Etiology and pathogenesis of chronic pancreatitis in adults", section on 'Pathogenesis'.)


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Literature review current through: Sep 2016. | This topic last updated: Oct 5, 2016.
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  1. Lagerlof HO. Pancreatic function and pancreatic disease: studied by means of secretin. Acta Med Scand 1942; 128:1.
  2. Chiray M, Jeandel A, Salmon A. L'exploration clinique du pancreas et l'injection intraveneuse de secretine purifiee. Presse Med 1930; 38:977.
  3. DREILING DA, HOLLANDER F. Studies in pancreatic function; preliminary series of clinical studies with the secretin test. Gastroenterology 1948; 11:714.
  4. Bae JM, Park JW, Yang HK, Kim JP. Nutritional status of gastric cancer patients after total gastrectomy. World J Surg 1998; 22:254.
  5. Sauniere JF, Sarles H. Exocrine pancreatic function and protein-calorie malnutrition in Dakar and Abidjan (West Africa): silent pancreatic insufficiency. Am J Clin Nutr 1988; 48:1233.
  6. Stevens T, Conwell DL. Pancreatic enzyme replacement and bile salt therapy (Chapter 12). In: Intestinal Failure and Rehabilitation, Seidner D, Steiger E, Matarese L (Eds), CRC Press, Boca Raton 2005.
  7. Descos L, Duclieu J, Minaire Y. Exocrine pancreatic insufficiency and primitive malnutrition. Digestion 1977; 15:90.
  8. Perez MM, Newcomer AD, Moertel CG, et al. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer 1983; 52:346.
  9. Bartel MJ, Asbun H, Stauffer J, Raimondo M. Pancreatic exocrine insufficiency in pancreatic cancer: A review of the literature. Dig Liver Dis 2015; 47:1013.
  10. DiMagno EP, Go VL, Summerskill WH. Relations between pancreatic enzyme outputs and malabsorption in severe pancreatic insufficiency. N Engl J Med 1973; 288:813.
  11. Toskes PP, Dawson W, Curington C, et al. Non-diabetic retinal abnormalities in chronic pancreatitis. N Engl J Med 1979; 300:942.
  12. Morán CE, Sosa EG, Martinez SM, et al. Bone mineral density in patients with pancreatic insufficiency and steatorrhea. Am J Gastroenterol 1997; 92:867.
  13. Dutta SK, Bustin MP, Russell RM, Costa BS. Deficiency of fat-soluble vitamins in treated patients with pancreatic insufficiency. Ann Intern Med 1982; 97:549.
  14. Nakamura T, Takebe K, Imamura K, et al. Fat-soluble vitamins in patients with chronic pancreatitis (pancreatic insufficiency). Acta Gastroenterol Belg 1996; 59:10.
  15. Chen WL, Morishita R, Eguchi T, et al. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function. Gastroenterology 1989; 96:1337.
  16. Glasbrenner B, Malfertheiner P, Büchler M, et al. Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder? Klin Wochenschr 1991; 69:168.
  17. Löser C, Möllgaard A, Fölsch UR. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Gut 1996; 39:580.
  18. Stein J, Jung M, Sziegoleit A, et al. Immunoreactive elastase I: clinical evaluation of a new noninvasive test of pancreatic function. Clin Chem 1996; 42:222.
  19. Domínguez-Muñoz JE, Hieronymus C, Sauerbruch T, Malfertheiner P. Fecal elastase test: evaluation of a new noninvasive pancreatic function test. Am J Gastroenterol 1995; 90:1834.
  20. Gullo L, Ventrucci M, Tomassetti P, et al. Fecal elastase 1 determination in chronic pancreatitis. Dig Dis Sci 1999; 44:210.
  21. Beharry S, Ellis L, Corey M, et al. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease? J Pediatr 2002; 141:84.
  22. Fischer B, Hoh S, Wehler M, et al. Faecal elastase-1: lyophilization of stool samples prevents false low results in diarrhoea. Scand J Gastroenterol 2001; 36:771.
  23. Lankisch PG, Schreiber A, Otto J. Pancreolauryl test. Evaluation of a tubeless pancreatic function test in comparison with other indirect and direct tests for exocrine pancreatic function. Dig Dis Sci 1983; 28:490.
  24. Niederau C, Grendell JH. Diagnosis of chronic pancreatitis. Gastroenterology 1985; 88:1973.
  25. Couper RT, Corey M, Durie PR, et al. Longitudinal evaluation of serum trypsinogen measurement in pancreatic-insufficient and pancreatic-sufficient patients with cystic fibrosis. J Pediatr 1995; 127:408.
  26. Ventrucci M, Pezzilli R, Gullo L, et al. Role of serum pancreatic enzyme assays in diagnosis of pancreatic disease. Dig Dis Sci 1989; 34:39.
  27. Jacobson DG, Curington C, Connery K, Toskes PP. Trypsin-like immunoreactivity as a test for pancreatic insufficiency. N Engl J Med 1984; 310:1307.
  28. Lambiase L, Forsmark CE, Toskes PP. Secretin test diagnoses chronic pancreatitis earlier than ERCP (abstract). Gastroenterology 1993; 104:315.
  30. Banwell JG, Northam BE, Cooke WT. Secretory response of the human pancreas to continuous intravenous infusion of pancreozymin-cholecystokinin (Cecekin). Gut 1967; 8:380.
  31. Ribet A, Tournut R, Duffaut M, Vaysse N. Use of caerulein with submaximal doses of secretin as a test of pancreatic function in man. Gut 1976; 17:431.
  32. Go VL, Hofmann AF, Summerskill WH. Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology 1970; 58:321.
  33. Valentini M, Cavallini G, Vantini I, et al. A comparative evaluation of endoscopic retrograde cholangiopancreatography and the secretin-cholecystokinin test in the diagnosis of chronic pancreatitis: a multicentre study in 124 patients. Endoscopy 1981; 13:64.
  34. Dobrilla G, Fratton A, Valentini M, et al. Endoscopic retrograde pancreatography and secretin-pancreozymin test in diagnosis of chronic pancreatitis: a comparative evaluation. Endoscopy 1976; 9:118.
  35. Mee AS, Girdwood AH, Walker E, et al. Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis. Gut 1985; 26:1257.
  36. Ketwaroo G, Brown A, Young B, et al. Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis. Am J Gastroenterol 2013; 108:1360.
  37. Rolny P, Jagenburg R. The secretin-CCK test and a modified Lundh test. A comparative study. Scand J Gastroenterol 1978; 13:927.
  38. Rolny P, Lukes PJ, Gamklou R, et al. A comparative evaluation of endoscopic retrograde pancreatography and secretin-CCK test in the diagnosis of pancreatic disease. Scand J Gastroenterol 1978; 13:777.
  39. Malfertheiner P, Büchler M, Stanescu A, Ditschuneit H. Exocrine pancreatic function in correlation to ductal and parenchymal morphology in chronic pancreatitis. Hepatogastroenterology 1986; 33:110.
  40. Braganza JM, Hunt LP, Warwick F. Relationship between pancreatic exocrine function and ductal morphology in chronic pancreatitis. Gastroenterology 1982; 82:1341.
  41. Heij HA, Obertop H, Schmitz PI, et al. Evaluation of the secretin-cholecystokinin test for chronic pancreatitis by discriminant analysis. Scand J Gastroenterol 1986; 21:35.
  42. Bozkurt T, Braun U, Leferink S, et al. Comparison of pancreatic morphology and exocrine functional impairment in patients with chronic pancreatitis. Gut 1994; 35:1132.
  43. Dreiling DA. Pancreatic secretory testing in 1974. Gut 1975; 16:653.
  44. Catalano MF, Lahoti S, Geenen JE, Hogan WJ. Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis. Gastrointest Endosc 1998; 48:11.
  45. Draganov P, George S, Toskes PP, Forsmark CE. Is a 15-minute collection of duodenal secretions after secretin stimulation sufficient to diagnose chronic pancreatitis? Pancreas 2004; 28:89.
  46. Moolsintong P, Burton FR. Pancreatic function testing is best determined by the extended endoscopic collection technique. Pancreas 2008; 37:418.
  47. Stevens T, Conwell DL, Zuccaro G Jr, et al. The efficiency of endoscopic pancreatic function testing is optimized using duodenal aspirates at 30 and 45 minutes after intravenous secretin. Am J Gastroenterol 2007; 102:297.
  48. Stevens T, Conwell DL, Zuccaro G, et al. Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects. Gastrointest Endosc 2004; 60:351.
  49. Stevens T, Conwell DL, Zuccaro G Jr, et al. A randomized crossover study of secretin-stimulated endoscopic and dreiling tube pancreatic function test methods in healthy subjects. Am J Gastroenterol 2006; 101:351.
  50. Stevens T, Conwell DL, Zuccaro G Jr, et al. A prospective crossover study comparing secretin-stimulated endoscopic and Dreiling tube pancreatic function testing in patients evaluated for chronic pancreatitis. Gastrointest Endosc 2008; 67:458.
  51. Albashir S, Bronner MP, Parsi MA, et al. Endoscopic ultrasound, secretin endoscopic pancreatic function test, and histology: correlation in chronic pancreatitis. Am J Gastroenterol 2010; 105:2498.
  52. Conwell DL, Zuccaro G, Purich E, et al. The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT). Am J Gastroenterol 2005; 100:1161.
  53. Denyer ME, Cotton PB. Pure pancreatic juice studies in normal subjects and patients with chronic pancreatitis. Gut 1979; 20:89.
  54. Ochi K, Harada H, Mizushima T, et al. Intraductal secretin test is as useful as duodenal secretin test in assessing exocrine pancreatic function. Dig Dis Sci 1997; 42:492.
  55. Gregg JA, Sharma MM. Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer. Am J Surg 1978; 136:569.
  56. Draganov P, Patel A, Fazel A, et al. Prospective evaluation of the accuracy of the intraductal secretin stimulation test in the diagnosis of chronic pancreatitis. Clin Gastroenterol Hepatol 2005; 3:695.
  57. Stevens T, Dumot JA, Zuccaro G Jr, et al. Evaluation of duct-cell and acinar-cell function and endosonographic abnormalities in patients with suspected chronic pancreatitis. Clin Gastroenterol Hepatol 2009; 7:114.
  58. Conwell DL, Zuccaro G Jr, Vargo JJ, et al. An endoscopic pancreatic function test with cholecystokinin-octapeptide for the diagnosis of chronic pancreatitis. Clin Gastroenterol Hepatol 2003; 1:189.
  59. Stevens T, Parsi MA. Update on endoscopic pancreatic function testing. World J Gastroenterol 2011; 17:3957.
  60. Lankisch PG. Exocrine pancreatic function tests. Gut 1982; 23:777.
  61. Lankisch PG. Secretin test or secretin-CCK test—gold standard in pancreatic function testing? Pancreatitis—concepts and classifications. In: Excerpta Medica, ICS 642, Gyre K, Singer MV, Sarles H (Eds), Amsterdam 1994. p.247.
  62. Law R, Lopez R, Costanzo A, et al. Endoscopic pancreatic function test using combined secretin and cholecystokinin stimulation for the evaluation of chronic pancreatitis. Gastrointest Endosc 2012; 75:764.
  63. Sun DY, Jiang YB, Rong L, et al. Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine insufficiency. Hepatobiliary Pancreat Dis Int 2003; 2:449.
  64. Ritz MA, Fraser RJ, Di Matteo AC, et al. Evaluation of the 13C-triolein breath test for fat malabsorption in adult patients with cystic fibrosis. J Gastroenterol Hepatol 2004; 19:448.
  65. Erturk SM, Ichikawa T, Motosugi U, et al. Diffusion-weighted MR imaging in the evaluation of pancreatic exocrine function before and after secretin stimulation. Am J Gastroenterol 2006; 101:133.
  66. Balci NC, Smith A, Momtahen AJ, et al. MRI and S-MRCP findings in patients with suspected chronic pancreatitis: correlation with endoscopic pancreatic function testing (ePFT). J Magn Reson Imaging 2010; 31:601.