Pancreatic insufficiency is a term describing the inability of the pancreas to produce enzymes necessary for the digestion of nutrients, resulting in malabsorption. The diagnosis is made based on clinical and laboratory criteria.
The symptoms of pancreatic insufficiency are primarily related to the progressive destruction of the exocrine pancreas. In the adult population, it is most frequently encountered in association with acute or chronic pancreatitis, pancreatic resection or neoplastic diseases of this organ . In children, on the other hand, the most common cause is cystic fibrosis . As the pancreas is unable to perform its function of releasing digestive enzymes into the duodenal lumen, the resultant malabsorption causes foul-smelling, bulky and loose stools abundant with fat (steatorrhea) that are difficult to flush away  . Steatorrhea can occur up to 2-3 times per day, usually after meals, despite normal intake of dietary fat, and is accompanied by abdominal pain of varying severity  . Over time, weight loss, anorexia, muscle wasting and flatulence ensue, while severe cases suffer from profound hypoalbuminemia that can manifest with leukonychia . In children, malabsorption causes poor growth and failure to thrive . Although the majority of symptoms are related to exocrine insufficiency, the decreasing output of insulin and glucagon, which are produced by the endocrine pancreas, can lead to diabetes mellitus and there is a very high risk of hypoglycemia, known as "brittle" diabetes . Apart from malabsorption-related complaints, signs of liposoluble vitamin deficiency can appear such as ecchymoses due to vitamin K deficiency, xerophthalmia and night blindness as a result of impaired vitamin A absorption, and ataxia or peripheral neuropathy in the setting of vitamin E deficiency  Muscle spasms, osteomalacia and osteoporosis may be related to vitamin D deficiency and consequent hypocalcemia .
To diagnose pancreatic insufficiency, it is necessary to perform a thorough workup, starting with a detailed patient history that can reveal the presence of comorbidities or pre-existing pancreatic conditions that might be considered as risk factors (alcoholism, acute/chronic pancreatitis, or tumors). After a meticulous physical examination, the obtained data should be sufficient to make a preliminary diagnosis, but further laboratory studies are necessary to support clinical suspicion . Initial blood work includes a complete blood count (CBC), glucose levels, ferritin, lipase, amylase, albumin and total protein content, and pancreatic tests, which may be indirect or direct. . 72-hour stool collection and determination of the coefficient of fat absorption (CFA) was one of the main indirect tests used, but inadequate patient compliance and introduction of novel techniques have displaced it from regular use  . Determination of fecal elastase, on the other hand, is a very reliable procedure that requires only one stool sample, but its sensitivity in early and mild insufficiency is limited  . Moreover, degradation of triglycerides through the 13C-mixed triglycerides breath test is recommended as well , which comprises ingestion of a small amount of 13C-marked triglycerides with a toasted bread and subsequent measurement of CO2 exhaled air, as 13C-triglycerides should be degraded in the intestinal lumen and metabolized in the liver . In the presence of decreased lipase activity, these fatty acids will not be degraded and a decreased CO2 content in exhaled air will be observed . Other notable noninvasive tests include fecal chymotrypsin determination and secretin-enhanced magnetic resonance cholangiopancreatography . The cholecystokinin (CCK) test, which requires specialized laboratory conditions, the secretin test, and the Lundh test are more invasive procedures that are chosen only if indirect tests fail to confirm the diagnosis   .