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Cystic fibrosis: Assessment and management of pancreatic insufficiency

Julie P Katkin, MD
Robert D Baker, MD, PhD
Susan S Baker, MD, PhD
Section Editors
Kathleen J Motil, MD, PhD
George B Mallory, MD
Melvin B Heyman, MD, MPH
Deputy Editor
Alison G Hoppin, MD


Pancreatic insufficiency is the most common gastrointestinal complication of cystic fibrosis (CF), affecting approximately 85 percent of patients at some time in their lives [1,2]. The major consequences of pancreatic insufficiency are due to fat malabsorption, which is caused by decreased production of pancreatic enzymes. As a result, patients are at risk for steatorrhea, malnutrition, and fat-soluble vitamin deficiencies.

The pathogenesis, clinical manifestations, diagnosis, and management of pancreatic insufficiency in children with CF will be discussed here. The nutritional consequences of this disorder and other gastrointestinal complications of CF are discussed separately. (See "Cystic fibrosis: Nutritional issues" and "Cystic fibrosis: Overview of gastrointestinal disease".)


Traditionally, patients with CF have been categorized as pancreatic sufficient (10 to 15 percent) and pancreatic insufficient (the remainder) [3]. It is now clear that pancreatic function in CF varies along a spectrum from normal to severely deficient. Patients with normal or near normal pancreatic function tend to have less severe lung disease, and their nutritional status is better than their counterparts who have more severe pancreatic dysfunction. Pancreatic function also varies with the age of the patient, tending to worsen over time.

Pancreatic function correlates strongly with genotype in patients with CF. Pancreatic insufficiency generally develops within the first few months of life in patients with two "severe" mutations of the CF transmembrane conductance regulator (CFTR) gene, including F508del, N1303K, G542X, and G551D (table 1) [4-6]. These severe mutations usually are from functional class I (defective CFTR protein synthesis), class II (defective CFTR protein processing), or class III (defective regulation/gating of the CFTR channel). By contrast, the presence of at least one "mild" mutation such as R117H or A445E usually is associated with pancreatic sufficiency [5,7]. These mild mutations tend to be from functional class IV (decreased CFTR channel conductance) or class V (reduced synthesis or trafficking). Of note, this genotype association is stronger for the pancreatic insufficiency phenotype, and much weaker for pulmonary disease phenotype. (See "Cystic fibrosis: Genetics and pathogenesis".)


Defective functioning of the CF transmembrane conductance regulator (CFTR) leads to impaired transport of chloride, sodium, and bicarbonate. As a result, water does not diffuse out of the cell into the mucus layer, leading to viscous epithelial secretions. The resultant protein-rich, viscous exocrine fluid becomes inspissated in the proximal pancreatic ducts, leading to their obstruction.  


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Literature review current through: Sep 2016. | This topic last updated: Oct 12, 2015.
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