Pancreatic exocrine insufficiency: causes, diagnosis and treatment

Introduction

Pancreatic exocrine insufficiency (PEI) occurs when the pancreas is unable to produce sufficient enzymes to aid digestion^​1​. As a result, patients may become malnourished owing to inadequate absorption of nutrients^​2​. In people with pancreatic illnesses, the incidence of PEI varies depending on the underlying cause. Globally, chronic pancreatitis is the most common cause of PEI, with 80–90% of patients experiencing symptoms^​3​. In patients with pancreatic cancers, 66–92% experience PEI^​4​. 

National Institute for Health and Care Excellence (NICE) guidance for the management of PEI in pancreatitis, published in 2018, recommends monitoring patients for symptoms of malabsorption and malnutrition — such as loose stools and weight loss — and ensuring that patients are referred to dietitians to determine if pancreatic enzyme replacement therapy (PERT) is required^​5​.

In pancreatic cancers, NICE guidance, published in 2018, recommends that all patients with unresectable pancreatic cancers should be initiated on PERT, while those with resectable cancers should be reviewed before and after resection to determine if PERT is required^​6​.

Pharmacists have a role in the review and management of patients with PEI. It is, therefore, important that they are able to recognise the presenting symptoms and understand how PEI can be managed using PERT. When reviewing patients taking PERT, recognition of symptoms of PEI may help to identify suboptimal dosing and provide an opportunity to optimise management. When patients are newly initiated on PERT, pharmacists play a crucial role in providing education on the correct use of PERT, including advising patients on ongoing PERT shortages^​7​.

Overview of normal pancreas function and the pathophysiology of PEI

The pancreas is a glandular organ with a dual function (see Figure)^​8,9​.

Any disease that destroys pancreatic tissue or blocks the ducts within the pancreas can cause PEI (see causes below). In cases of impaired pancreatic function, patients may present with endocrine insufficiency — which is characterised by a reduction in functional islet cell mass and reduced insulin secretion — and subsequently results in impairments of glucose tolerance^​10,11​. Patients may also present with exocrine insufficiency owing to inadequate production of pancreatic enzymes to aid digestion^​1​.

Causes

Conditions that result in the loss of functional pancreatic parenchyma can cause disruptions to normal pancreatic exocrine function^​12​. Causes of PEI include inflammatory conditions of the pancreas — for example:

• Acute pancreatitis: an acute inflammatory response resulting from injury to the pancreas^​13​;
• Chronic pancreatitis: pancreatic inflammation owing to repeated episodes of acute pancreatitis, resulting in irreversible damage to the pancreas^​14​.

The development of pancreatitis may stem from gallstones, excessive alcohol intake, hereditary factors or autoimmune conditions^​5​.

Malignant or premalignant conditions may also cause PEI. Healthcare professionals should evaluate symptoms and consider whether PERT is appropriate for patients with the following pathologies: 

• Pancreatic cancer;
• Intraductal papillary mucinous neoplasm;
• Ampullary cancer;
• Duodenal cancer;
• Cholangiocarcinoma;
• Pancreatic neuroendocrine tumours^​15​.

Signs and symptoms

Patients with PEI commonly present to primary and secondary care with the symptoms shown in Table 1^{​16–21​}.

Patients presenting with jaundice, unintentional weight loss or ongoing symptoms of PEI with no known underlying pancreatic illnesses should be urgently referred for further investigations to rule out pancreatic malignancy^​22​.

Diagnosis

Owing to the range of symptoms associated with PEI (as seen in Table 1), patients may present to community pharmacies, GP surgeries or A&E. If presenting to community pharmacy, patients should be referred to their GP for further review.

PEI is diagnosed by the presence of chronic diarrhoea/steatorrhea (i.e. excessive fat in the stool) and abdominal pain in conjunction with identified risk factors, such as pancreatic disorders, alcohol excess, diabetes, weight loss, malaise and suspicion of malignancy^​23​.

If the diagnosis is unclear, additional tests can be carried out to confirm PEI. As per the ‘Consensus for the management of pancreatic exocrine insufficiency UK practical guidelines’, published in 2021, FEL-1 testing is recommended^​2​. FEL-1 testing is a marker of pancreatic secretion of enzymes and is valuable in supporting a diagnosis of PEI in the presence of symptoms of malabsorption and malnutrition (see Table 1)^​2​. FEL-1 testing is non-invasive and is undertaken using a small amount of faeces^​2​. If samples are contaminated by water, false-positive results may occur. Therefore, stools classified as type 7 on the Bristol stool chart should not be used^​2​. 

When reviewing FEL-1 results, the following ranges can be used to identify the severity of PEI^​24​.

As FEL-1 only tests for human elastase, administration of PERT does not have an effect on results, as PERT products are of porcine origin^{​2,25–31​}.

In the following conditions, the likelihood of developing PEI is high. Therefore, patients are likely to benefit from PERT^​2​. In these patient groups, FEL-1 testing is not required as negative predictive values of FEL-1 do not prevent treatment initiation^​2​: 

• Pancreatic cancer;
• Total pancreatectomy; 
• Symptomatic chronic pancreatitis;
• Severe necrotising pancreatitis.

In patients with symptoms of PEI without known associated conditions, FEL-1 testing should be carried out alongside cross-sectional imaging to exclude obstructive tumours^​2​. If a pancreatic cause has not been identified, FEL-1 tests should be repeated^​2​.

Pancreatic enzyme replacement therapy

There are several forms of PERT available, with each preparation containing different quantities of pancreatic enzymes. Therefore, these products are not directly interchangeable ^{​25–31​}.

When initiating treatment, the recommended dose of PERT is 50,000 units of lipase per meal and 25,000 units of lipase per snack^​32​. Following the initiation of PERT, patients should be reviewed after four to six weeks to determine if symptom control has been achieved^​23​.

When symptom control is achieved, patients with pancreatic cancer should receive ongoing monitoring for symptoms of PEI every four to six weeks^​23​. In those patients with other pancreatic conditions, six-monthly monitoring is recommended^​23​. If symptom control is not achieved, patients should be referred to a dietitian, and doses should be titrated according to the level of response^​23,32​. When correct dosing is achieved, symptoms of PEI should be normalised^​32​.

PERT shortage

Current supply issues with PERT may result in patients experiencing difficulties or delays in obtaining this medicine^​36​. As supply issues are predicted to continue until 2026, patients may need to be switched to alternative PERT products, and additional symptomatic management may need to be implemented^​36​. More information about the PERT shortage can be found here.

A joint position statement, published in 2024, regarding the clinical management of this shortage in adult patients suggests:

• Consider prescribing a proton pump inhibitor/H2 receptor antagonists to reduce acid degradation and improve PERT efficacy;
• Consider prescribing loperamide to reduce faecal urgency and diarrhoea, where infective or obstructive causes have been ruled out;
• Consider prescribing Buscopan (hyoscine butylbromide; Sanofi) for abdominal discomfort;
• Consider multivitamin and mineral replacement and calcium and vitamin D supplementation for patients not already taking these medicines^​36​.

As PERT is essential for maintaining control of PEI symptoms, clinicians should be mindful that supply issues may result in anxiety and concern for patients. Patients should be reviewed on a case-by-case basis, and where patients are reporting weight loss or unmanageable symptoms owing to an inability to obtain PERT, further advice should be sought from local dietetics teams^​36​. Additional information can be found in: ‘How to navigate and ensure effective patient communication about medicines shortages’.

As each PERT is not directly interchangeable, when patients need to be switched to alternative products, the conversions shown in Table 4 can be used.

Patient counselling

When administering PERT, patients should be provided with the following information:

• PERT should be taken with all meals and snacks containing fat and drinks containing >50% of milk;
• Half of the PERT dose should be taken at the start of the meal, with the other half being spread throughout the remainder of the meal;
• PERT should be swallowed whole and should not be chewed or crushed, as this may reduce enzyme effectiveness and cause oromucosal irritation;
• If a drink is needed to assist with swallowing, hot drinks should be avoided as they may reduce enzyme effectiveness^​33​.

In patients with swallowing difficulties:

• Capsules can be opened, and the enzymes should be administered in a spoonful of soft acidic food, such as jam or fruit puree — this is because pH >5.5 may disrupt the coating on the granules inside the capsules and reduce efficacy;
• Once opened, the capsule contents should be taken immediately;
• The capsule contents should be washed down with a cold drink to ensure that granules do not remain in the mouth, as this may cause oromucosal irritation^​33,34​. 

On the initiation of PERT, patients should be made aware of common side effects, including abdominal distension, constipation, nausea and vomiting^​35​. If experiencing adverse effects, patients should report this to a healthcare professional. In the case of serious adverse effects, such as hypersensitivity reactions, patients should discontinue PERT and seek further guidance from the prescribing clinician.

Patients should understand that it may take several days for PERT to be effective, and it is beneficial to keep a food diary to help monitor symptoms and guide dose adjustments^​33​. Patients should understand that dietary fat restriction is not routinely recommended, as this may exacerbate malnutrition^​2​.  

As nutrient deficiencies are common, all patients on PERT should have vitamin and micronutrient screening on initiation and at regular intervals (six months if deficiency detected and annually thereafter)^​23​.

Case study

A 60-year-old female presented to A&E with central, epigastric pain, which was accompanied by nausea and two episodes of vomiting within a 24-hour period. Her past medical history included hypertension and two previous hospital admissions for acute pancreatitis. 

The patient’s medication history included amlodipine 5mg once daily and loperamide 2mg up to four times per day as required, which were purchased over the counter. Once questioned about the indication for loperamide, the patient reported ongoing loose stools, which was accompanied by epigastric pain and unintentional weight loss of 5kg. 

On review of her social history, the patient reported that she was a non-smoker and drinks ~15–20 units of alcohol on weekends. Following her previous admission for acute pancreatitis, she was abstinent from alcohol for three months but states that she restarted drinking within a social setting. 

Upon completing the medication history, the pharmacist identified symptoms of PEI associated with a history of acute pancreatitis, as well as unintentional weight loss. The pharmacist then highlighted this to the medical team for further review. 

Following this, the patient had a blood test which showed normal urea and electrolytes and liver function tests. Owing to ongoing diarrhoea symptoms, FEL-1 testing was undertaken, which was reported as 80 µg/g stool. The patient also had an abdominal CT, which showed evidence of acute pancreatitis and evidence of established chronic pancreatitis.

The presence of chronic pancreatitis, unintentional weight loss, loose stools and an FEL-1 result of 80 µg/g indicated severe PEI, requiring treatment with PERT. 

Initially, the patient was prescribed 50,000 units of lipase with meals and 25,000 units of lipase with snacks. As this was a new medicine, the pharmacist provided counselling regarding the indication for PERT, as well as advice regarding the administration and common side effects associated with treatment. 

To manage expectations of treatment, the pharmacist highlighted that it may take several days for PERT to be effective and advised keeping a food diary to help monitor symptoms. As alcohol is a causative factor for chronic pancreatitis, the pharmacist provided advice regarding abstinence from alcohol to avoid future pancreatitis flare-ups.

During the inpatient admission, the patient was referred to a dietitian for further review of PEI symptoms, and a vitamin and mineral screen was undertaken to test for deficiencies. To ensure ongoing review, the patient was referred to community dietitians on discharge for monitoring of PEI symptoms and optimisation of PERT dosing. She was also referred to her local hepatobiliary and pancreatic team for ongoing review.

• This article was amended on 8 May 2025 to update a reference and correct an error in Table 3