Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas

Table 1 Causes of pancreatic insufficiency

Chronic pancreatitis
Primary pancreatic insufficiency
Agenesis of the pancreas
Congenital pancreatic hypoplasia
Shwachman–Diamond syndrome
Johanson–Blizzard syndrome
Adult pancreatic lipomatosis or atrophy
Isolated lipase or colipase deficiency
Pancreatic resection
Pancreatic cancers
Secondary pancreatic insufficiency
Mucosal small bowel disease: Decreased cholecystokinin release
Somastatinoma or exogenous somatostatin analog intake: Decreased pancreatic secretion
Gastrinoma: Intraluminal destruction of enzymes
Surgery and Billroth II anastomosis: Poor mixing or decreased hormone release, disturbance of innervations
Periampullary tumors (pancreatic duct obstruction)

Modified from reference 155.

Table 2 Pathogenesis of maldigestion

Mechanism	Explanation
Decreased pancreatic production	Lack of functional tissue or decreased endogenous neurohormonal stimulation
Decrease in delivery	Pancreatic duct obstruction
Decreased activation	Low duodenal pH
Premature enzymatic degradation	Decreased contact time due to increased motility, impaired interaction with chyme and biliary salts, and intestinal bacterial overgrowth

Table 3 Indirect diagnostic tests for evaluating pancreatic exocrine insufficiency

Test	In favour	Against
CFA	Gold standard	72 h stool collection; 100 g standard diet; no simultaneous PERT; not pancreas specific
Acid steatocrit	Linear correlation with CFA also in a single sample; Good as screening	High fat diet needed; 24-72 h stool collection is ideal
Fecal elastase 1	Single stool sample; PERT can be continued	Poor sensitivity in mild EPI, watery stools and small bowel disease
13C-mixed triglyceride breath test	Simple; Also for mild forms of EPI and therapy assessment	Requires further validation
Fecal chymotrypsin	Good for compliance control; Single small stool sample	Sensitivity low for clinical practice (chymotrypsin is variably inactivated during intestinal transit); not for mild EPI; watery stools decrease enzyme activity; PERT must be discontinued
Secretin-enhanced magnetic resonance cholangiopancreatograpgy	Morphological and semi-quantitative functional changes	Requires further validation
Nutritional status (magnesium < 2.05 mg/dL, ↓prealbumin, ↓albumin, ↓retinol binding protein, ↓ferritin, ↓hemoglobin)	Simple	Requires further validation

CFA: Coefficient of fat absorption; PERT: Pancreatic enzyme supplementation therapy; EPI: Pancreatic exocrine insufficiency.

Table 4 Fecal elastase 1 concentrations in type 1 and type 2 diabetes mellitus n (%)

Ref.	Type 1 DM			Type 2 DM
	Overall	FE-1 (100-200μg/g)	FE-1 (< 100μg/g)	Overall	FE-1 (100-200μg/g)	FE-1 (< 100μg/g)
Hardt et al[80]	322	73 (23)	92 (28)	697	108 (15)	138 (20)
Vesterhus et al[81]	140	10 (7)	16 (11)	63	2 (3)	6 (9)
Larger et al[82]	195	28 (14)	38 (19)	472	35 (7)	50 (10)
Icks et al[83]	112	22 (20)	29 (26)
Cavalot et al[84]	37	17 (46)	4 (11)
Rathmann et al[85]				544	100 (18)	65 (12)
Nunes et al[86]				42	6 (14)	9 (21)
Yilmaztepe et al[87]				32	9 (28)	1 (3)
Overall	837	158 (18.9)	188 (22.5)	1933	275 (14.2)	283 (14.6)

DM: Diabetes mellitus; FE-1: Fecal elastase-1.