E-Poster Presentation 63rd Endocrine Society of Australia Annual Scientific Meeting 2020
A Painful Family (#134)
Case Presentation
A 43-year-old white female (FH) was seen in the Hunter alliance diabetes clinic (integrated diabetes clinic). She was diagnosed with type 2 diabetes three years ago and was on metformin 1g twice daily and gliclazide 30mg once a day. The Hba1c was 7.1%. FH also had well-managed eczema and coeliac disease which was diagnosed about five years ago based on a history of recurrent episodes of diarrhoea. There was no biochemical or histological confirmation of coeliac disease.
FH has recurrent pancreatitis since the age of 10. The episodes could present as mild abdominal symptoms to severe episodes of pancreatitis needing hospital admission for resuscitation.
FM has many family members with pancreatic disease (Figure 1). Her mother and maternal grandmother died from pancreatic cancer in their 60s after experiencing decades of recurrent pancreatitis. FMs brother, maternal Aunt and their children have recurrent pancreatitis. FH has two daughters, age 20 and 10 who have recurrent pancreatitis, which started at the age of 2 and 5 respectively. Several family members’ committed suicide for severe pain associated with pancreatitis.
FH has had several abdominal imaging over many years, and the most recent abdominal ultrasound in 2015 showed a pancreas with fatty infiltration with calcification. The pre-contrast CT scan showed significant pancreatic duct calcification consistent with sequala of recurrent episodes of chronic pancreatitis. The routine biochemistry was normal, and the coeliac screen was negative.
The strong family history suggested a familial cause of pancreatitis. We conducted genetic testing, which was positive for a pathogenic mutation in the PRSS1 gene. We have offered genetic testing for other family members. We started basal/bolus insulin to manage the diabetes and discontinued oral anti-diabetic medications. We also started pancreatic hormones 20000units (Creon) with each meal which significantly reduced the diarrhoea.FM remains concerned about the risk for herself and her children having pancreatic cancer which is known to have a poor prognosis. We are in discussion with our local gastroenterology service to decide on the best screening programme for FH and similar patients.
Discussion
Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable penetrance causing recurrent pancreatitis. Epidemiological data shows that between five to ten percent of acute pancreatitis in children is from HP. The majority of families originate from the United States and Europe (Italy. Germany and Turkey). One family of Aboriginal descent was reported from New Zealand to carry the PRSS1 R122H variant1.
The pathophysiology is based on unregulated activation of trypsinogen to trypsin leading to pancreatic inflammation. HP is generally caused by gain-of-function mutations in the cationic trypsinogen gene (PRSS1), although rare kindreds have been identified2(table1).
The clinical presentation varies from mild abdominal discomfort to severe acute pancreatitis, and cases vary substantially between individuals and families due to gene-gene and gene-environment interactions4. The majority of the patient would have had at least one episode of pancreatitis before the age of 20.
The complications occur later in life as a result of recurrent pancreatic insult. The exocrine dysfunction occurs typically early in the disease course, present as recurrent episodes of diarrhoea, malabsorption and malnutrition. The endocrine dysfunction follows a similar trajectory with some patients developing diabetes in their first decade of life with the risk increases with age. The most feared and severe complication which is pancreatic cancer mostly occurs after the 5th decade6 (figure 2).
Early recognition of HP is vital, and management should comprise a multidisciplinary team involving a gastroenterologist, endocrinologist and general surgeon. The abdominal pain is managed with paracetamol, ibuprofen and opiates. There is evidence for using antioxidants which can reduce the oxidative stress in acinar cells which helps to reduce the pain7. For opiate naïve/dependent patients, pancreatectomy with islet cell auto transplantation can be considered8. The exocrine insufficiency is managed with pancreatic enzyme supplements with meals.
HP can lead to brittle diabetes following the destruction of both alpha and beta cells in the islets. Insulin secretion can be variable, and most patients will need insulin early in the course of diabetes6.
Many studies from United States and Europe show that the occurrence of pancreatic cancer in HP was significantly higher than age- and sex-matched populations3. The risk goes up exponentially with older age5. The International Cancer of the Pancreas Screening (CAPS) Consortium summit made several recommendations on screening for patients with increased risk for familial pancreatic cancer. It highlighted the importance of early screening to detect margin negative pancreatic cancer and the screening of first-degree relatives. Initial screening should include endoscopic ultrasonography (EUS) and MRI/magnetic resonance cholangiopancreatography, not CT or abdominal ultrasound. Total pancreatectomy to prevent pancreatic cancer has been considered; however, long-term survival data is lacking3, 4.
Learning points
1 Hereditary pancreatitis should be considered in patients with diabetes who have a history of pancreatitis
2 Early initiation of insulin is warranted
3 Exocrine deficiency should be addressed with pancreatic enzyme supplementation
4 The patient needs to be managed by an MDT consist of an endocrinologist, gastroenterologist and a sergeant with a well-planned screening programme to detect pancreatic cancer.
