Pancreatic Exocrine Insufficiency

Written by Daniel de la Iglesia-Garcia and Dana Sochorova

Definition and Clinical Presentation

Pancreatic Exocrine Insufficiency is defined as a significant reduction in the secretion and/or suboptimal activity of pancreatic enzymes necessary for the normal digestion of nutrients. This condition leads to nutrient malabsorption, causing various intestinal symptoms and nutritional deficiencies. As it often presents as a symptom of other diseases, it is challenging to determine the overall prevalence.

The clinical manifestations of pancreatic exocrine insufficiency are a combination of signs and symptoms, where the intestinal effects are due to microbial digestion and the systemic effects are due to micro- and macronutrients’ maldigestion and malabsorption. These consequences can affect quality of life and put patients at risk of long-term malnutrition-related complications.

Clinical presentation

Etiology

The causes of pancreatic exocrine insufficiency are classified into three main groups: 1) loss of functional pancreatic parenchyma, 2) inhibition or inactivation of pancreatic secretion and 3) disruptions in the timing of pancreatic enzyme release after eating. The loss of pancreatic tissue is a major factor leading to pancreatic exocrine insufficiency and arises from several conditions. Chronic pancreatitis is the most common cause, followed by pancreatic cancer and cystic fibrosis. Key risk factors for pancreatic exocrine insufficiency in patients with pancreatic cancer include tumor location in the pancreatic head, extensive tissue loss due to atrophy of parenchyma (around 90%), obstruction, and the surgical removal of pancreatic tissue.

Summary of main etiologies

Adapted from Lindkvist B. World J Gastroenterol. 2013;19(42):7258-7266, licensed under CC BY-NC 4.0

1. Loss of Functional Pancreatic Parenchyma

The loss of pancreatic tissue is a major factor leading to pancreatic exocrine insufficiency and arises from several conditions.⁷ Chronic pancreatitis is the most common cause, followed by pancreatic cancer and cystic fibrosis.^1,5,7 Key risk factors for pancreatic exocrine insufficiency in patients with pancreatic cancer include tumour location in the pancreatic head, extensive tissue loss (around 90%), obstruction and the surgical removal of pancreatic tissue.^1,7 The latter can result in preoperative pancreatic exocrine insufficiency through pathways such as pancreatic atrophy and fibrosis due to duct obstruction.⁷

In addition, cystic fibrosis is associated with obstruction and damage to the pancreatic duct.^7,8 Nearly 90% of patients with cystic fibrosis experience pancreatic exocrine insufficiency.^7,8

2. Inhibition of Pancreatic Secretion

Pancreatic insufficiency can result from an obstruction of the pancreatic duct, decreased endogenous stimulation or intraluminal inactivation, as observed in Zollinger-Ellison syndrome, where acid hypersecretion and decreased pH lead to acid inactivation of pancreatic enzymes in the upper small intestine.⁷

3. Postcibal Pancreatic Asynchrony

Surgical resections of the stomach, small intestine and oesophagus can lead to pancreatic exocrine insufficiency by causing gastrointestinal asynchrony and reduced endogenous stimulation.⁷ These resections are mainly related to bariatric surgery⁹

Additional risk factors

Diagnosis

Patients with mild pancreatic exocrine insufficiency may be asymptomatic or experience minimal symptoms, such as slight abdominal discomfort and bloating, with bowel movements appearing normal.^1,3,4 As pancreatic exocrine insufficiency progresses, he ability to digest fats and proteins deteriorates, leading to symptoms such as weight loss, bloating, cramping, and increased flatulence.^1,^3,4 Overt steatorrhea – characterized by loose, greasy and foul-smelling stools that are hard to flush – occurs when approximately 90% of the pancreatic gland function is lost.⁴

Diagnosing pancreatic exocrine insufficiency requires a comprehensive evaluation of symptoms, nutritional status, and pancreatic function in an appropriate clinical context. pancreatic exocrine insufficiency requires careful differential diagnosis, because its symptoms can mimic those of other gastrointestinal disorders, such as small intestinal bacterial overgrowth or celiac disease. The diagnostic work-up for pancreatic exocrine insufficiency is indicated in the presence of pre-existing high-risk conditions such as cystic fibrosis, acute necrotizing pancreatitis, and chronic pancreatitis as well as pancreatic cancer or previous pancreatic surgery.

Pancreatic function tests

In clinical practice, the recommended pancreatic function test is faecal elastase-1 due to its availability and ease of use. Faecal elastase-1 concentration reflects the secretory capacity of the pancreas, however, it is not recommended for patients with mild to moderate pancreatic exocrine insuffiency due to potential sensitivity limitations. An faecal elastase-1concentration of <200 mcg/g is deemed abnormal, with levels <100 mcg/g indicative of pancreatic exocrine insuffiency and levels between 100 and 200 mcg/g onsidered indeterminate. Other diagnostic methods include a breath test measuring the intestinal breakdown of a 13C-labelled fatty substrate and measurements of serum trypsinogen and faecal C chymotrypsin (see page pancreatic function tests). Milder forms of pancreatic exocrine insuffiency might occur due to duodenal mucosa injuries, as in untreated celiac disease, affecting micronutrient, lipid and fat-soluble vitamin absorption.² Conditions like Zollinger-Ellison syndrome, which increase duodenal acid levels, can also cause pancreatic exocrine insuffiency by leading to pancreatic enzyme degradation.²Furthermore, additional lifestyle factors and ductal changes can increase the risk of developing pancreatic exocrine insuffiency, particularly in the context of chronic pancreatitis, where the risk exceeds 80%.²

Indirect indicators including nutritional parameters like prealbumin, retinol-binding protein, transferrin, magnesium, ferritin, and changes in haemoglobin must therefore also be considered.¹

Comprehensive overview of diagnosis and management

Management

Pancreatic exocrine insuffiency covers a spectrum of conditions, some with well-understood associations to enzyme insufficiency and others where the connections are less defined.⁷ This variability calls for a personalised, adaptable management strategy that includes pancreatic enzyme replacement therapy (PERT), dietary adjustments and continuous monitoring, aiming to effectively meet the complex needs of patients with pancreatic exocrine insuffiency.⁴

To optimise patient outcomes and reduce long-term sequela of untreated pancreatic exocrine insuffiency, early identification of the signs and symptoms, appropriate testing and personalised management are crucial.²

Treatment options for pancreatic exocrine insufficiency

Pancreatic Enzyme Replacement Therapy

Beginning pancreatic enzyme replacement therapy promptly after diagnosing pancreatic exocrine insufficiency is important for addressing the fundamental issue of enzyme deficiency.^2,6,7,10

The mechanism of action for pancreatic enzyme replacement therapy involves the use of microgranules approximately 1-1.5 mm in size, designed to pass uninhibited through the pylorus with ingested food.¹ When they reach the duodenum, the alkaline environment facilitates the release and activation of enzymes at the optimal site for digestion, aided by the dissolution of the acid-resistant enteric coating on the pills.¹ To closely mimic postprandial enzyme output following a meal, pancreatic enzyme replacement therapy capsules should be consumed with food.^1,2

The main aim of pancreatic enzyme replacement therapy is to relieve symptoms and support normal digestion, with dosage customised to achieve these objectives.¹ Initial dosing recommendations are between 25,000 and 50,000 units of lipase per meal. For patients with more severe pancreatic exocrine insufficiency, such as after pancreaticoduodenectomy, a higher starting dose may be necessary. It is important to note that dosages exceeding 72,000 units per meal have been linked to rare cases of hypersensitivity or allergic reactions.^1,2 For patients with cystic fibrosis, there have been reports of fibrosing colonopathy associated with high-dose pancreatic enzyme replacement therapy, highlighting the necessity of adjusting dosage based on individual response and tolerance.⁷

Nutritional Management

Incorporating a dietary evaluation by a qualified dietitian is important to identify nutritional needs and specific deficits.² This evaluation helps tailor dietary recommendations to support the overall management of pancreatic exocrine insufficiency, ensuring patients receive balanced nutrition that accommodates their condition’s unique demands.²

Regular supplementation and monitoring of fat-soluble vitamins (A, D, E and K) are essential elements of a comprehensive care strategy for patients with pancreatic exocrine insufficiency.² Due to malabsorption issues associated to pancreatic exocrine insufficiency, individuals face an increased risk of vitamin deficiencies, necessitating consistent evaluation and supplementation to maintain health and prevent complications.²

This lecture was part of a satellite symposium sponsored by Nordmark, held at the annual meeting of the European Pancreatic Club (EPC) in Santiago de Compostela, Spain, on Thursday, June 27th 2024.

References

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