Hypertriglyceridaemia Induced Acute Pancreatitis

Hypertriglyceridaemia Induced Acute Pancreatitis

A young man is admitted to the surgical unit with several months of worsening abdominal pain. It has become much more severe over the last 24 hours. A CT scan shows evidence of acute pancreatitis with no gallstones or biliary duct dilatation.. He is normally well with no history of alcohol excess. His triglyceride level is elevated at 83.7mmol/L and a diagnosis of hypertriglyceridaemia induced acute pancreatitis is made. 

What is hypertriglyceridaemia induced acute pancreatitis and how is it treated?

Dave Slessor

Hypertriglyceridaemia (HTG) can be inherited or secondary to a number of causes including diabetes mellitus, obesity, alcohol, hypothyroidism, and human immunodeficiency virus (1). Medications such as propofol (2) and anti-retroviral drugs (1) have also been implicated.

HTG has been reported to cause 6.5% of all cases of acute pancreatitis (AP) (3) and over 50% of cases of AP in pregnancy (4). In HTG induced AP the amylase level is often within the normal range (5). There is some evidence that patients with AP secondary to HTG have an increased severity of illness compared to cases of AP secondary to other causes. However, this finding has not been reproduced in all studies (3).

In the literature there are two widely quoted theories as to the mechanism through which HTG leads to AP. The first suggests that in the presence of increased levels of triglyceride (TG) there is an increase in hydrolysis of TG by pancreatic lipase. Free fatty acids are released and accumulate which results in capillary plugging leading to ischaemia and necrosis. The acidic environment activates trypsinogen and the initiation of AP (1). The second theory is that HTG leads to chylomicrons being present in the circulation. The chylomicrons may impair blood flow in the pancreas leading to ischaemia (6).

A number of different treatments have been used to try and lower TG levels. Insulin promotes the synthesis of lipoprotein lipase which hydrolyses TG into fatty acids and glycerol and facilitates the storage of the fatty acids in adipocytes (1). Anderson reported a case series of 26 patients with HTG induced AP (7). Six patients with normoglycaemia were managed with standard therapy of intravenous fluids, ‘nil by mouth’ and supportive care. Twenty patients with hyperglycaemia were treated with standard therapy and an insulin infusion. In the insulin group the initial mean TG level was 46.6mmol/l compared with 31.6mmol/l in the standard group. By day five 79% of patients in the insulin group had normal TG levels compared with 66% in the standard group. Mortality was 15% in the insulin group compared with 0% in the standard therapy. The results suggest that insulin infusions more rapidly decrease TG levels than standard treatment. However, no outcome benefit occurred. This was a non-randomised study on a small number of patients. Other than the TG level we are not told any of the baseline characteristics and therefore it is difficult to compare the two groups, particularly with regards to mortality outcomes. The definition of AP was an amylase level of more than twice the upper limit of normal. This would not be considered the gold standard and therefore the patients included in the study may not be representative of patients diagnosed with HTG induced AP in other institutions.

Heparin promotes the release of lipoprotein lipase thereby decreasing TG levels (1). Berger reports the use of intravenous heparin infusions in CT proven AP secondary to HTG in four patients (8). Three of the patients had pancreatic necrosis. The TG level decreased from between 14.7-80.4mmol/l on presentation to less than 10mmol/l on day three. Two of these patients were also treated with insulin infusions. There were no complications related to the heparin infusion.

Plasmapheresis has been used to remove TG and chylomicrons from the circulation. Kyriakidis used this strategy in nine patients admitted with HTG induced AP that did not respond to standard treatment within 24 hours (5). They reported that the majority of patients treated with plasmapheresis had improvement in pain scores within thirty minutes and the TG level returned to normal within one session. This was a retrospective, non-randomised study without a comparison group. Therefore even though the TG level was lower post-plasmapheresis we do not know if this treatment improved patient outcomes.

Dunne reports a case of pancreatitis with a TG level of 138 that returned to normal within 4 days with fluids only (9). This questions the need for any of the above treatments.

Longer term maintenance therapy for HTG has been demonstrated with various treatments included low fat diets, statins, fibrates, niacin and fish oil (10).


Lessons Learnt:

HTG induced AP is more common than I previously thought and a normal amylase level is consistent with the diagnosis. TG levels may decrease with standard treatment of nil by mouth and supportive care. Other treatments that have been used are insulin, heparin and plasmapheresis. These treatments may provide a more rapid correction of TG levels compared to standard care. However, currently we do not know if this improves outcomes. Long term maintenance therapy for HTG includes fibrates and fish oil.


References

  1. Poonuru S, Pathak SR, Vats HS, Pathak RD. Rapid reduction of severely elevated serum triglycerides with insulin infusion, gemfibrozil and niacin. Clinical medicine & research. 2011;9(1):38-41.
  2. Devlin JW, Lau AK, Tanios MA. Propofol‐Associated Hypertriglyceridemia and Pancreatitis in the Intensive Care Unit: An Analysis of Frequency and Risk Factors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2005;25(10):1348-52.
  3. Fillenwarth R, Rejowski B, Pitt H, Cote G, Zyromski N. Does Hypertriglyceridemia Cause More Virulent Acute Pancreatitis? Journal of Surgical Research. 2013;179(2):191-.
  4. Chang C-C, Hsieh Y-Y, Tsai H-D, Yang T-C, Yeh L-S, Hsu T-Y. Acute pancreatitis in pregnancy. Zhonghua yi xue za zhi= Chinese medical journal; Free China ed. 1998;61(2):85.
  5. Kyriakidis A, Raitsiou B, Sakagianni A, Harisopoulou V, Pyrgioti M, Panagopoulou A, et al. Management of acute severe hyperlipidemic pancreatitis. Digestion. 2006;73(4):259-64.
  6. Gan SI, Edwards AL, Symonds CJ, Beck PL. Hypertriglyceridemia-induced pancreatitis: A case-based review. World Journal of Gastroenterology. 2006;12(44):7197.
  7. Anderson F, Mbatha S, Thomson S. The early management of pancreatitis associated with hypertriglyceridaemia. South African Journal of Surgery. 2011;49(2):82-4.
  8. Berger Z, Quera R, Poniachik J, Oksenberg D, Guerrero J. heparin and insulin treatment of acute pancreatitis caused by hypertriglyceridemia. Experience of 5 cases]. Revista medica de Chile. 2001;129(12):1373.
  9. Dunne MJ, Shenkin A, Imrie CW. MISLEADING HYPONATRÆMIA IN ACUTE PANCREATITIS WITH HYPERLIPÆMIA. The Lancet. 1979;313(8109):211.
  10. Oh RC, Lanier JB. Management of hypertriglyceridemia. American family physician. 2007;75(9):1365.

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