Triglyceride-induced pancreatitis accounts for 4% of all episodes of acute pancreatitis and as many as 56% of cases in pregnancy. One study revealed that the risk for pancreatitis was 5% at triglyceride levels > 1000 mg/dL and 10%-20% at levels > 2000 mg/dL. A triglyceride level > 1000 mg/dL has been used as a cutoff for the diagnosis; however, the risk for pancreatitis progressively increases with serum levels and can occur even at levels as low as 400 mg/dL. In addition, triglyceride levels can rapidly trend down soon after symptoms start because the decrease in oral intake and fasting will lower the triglyceride-rich chylomicrons in the serum. An elevation in serum triglycerides during acute pancreatitis has traditionally been associated with increased lipolysis, and thus the diagnosis is often discounted. However, a high index of suspicion is needed if the traditional causes seem unlikely and additional risk factors are present. Once the pancreatitis has resolved, serial triglyceride levels need to be obtained.
The exact mechanism of pancreatitis is not well understood, but it is believed to be secondary to free fatty acids generated from the breakdown of triglycerides by pancreatic lipase. These free fatty acids can cause pancreatic cell injury and ischemia, in addition to the inflammatory response caused by the pancreatitis itself that leads to tissue injury.
The etiology of elevated triglycerides is divided into primary and secondary causes. Primary causes are genetic mutations in lipid metabolism that lead to severe hypertriglyceridemia and can predispose to pancreatitis. These include Fredrickson classification type I, IV, and V dyslipidemias, also known as familial hyperchylomicronemia, familial hypertriglyceridemia, and combined hypertriglyceridemia, respectively. Types I and V typically present with hypertriglyceridemia early in life, whereas type IV presents later and is usually triggered by a secondary factor. Secondary causes of elevated triglycerides are environmental and include poorly controlled diabetes, obesity, hypothyroidism, and alcohol use disorder. Moreover, some medications have been implicated in hypertriglyceridemia leading to pancreatitis, including estrogens, clomiphene, tamoxifen, propofol, beta-blockers, protease inhibitors, olanzapine, mirtazapine, valproic acid, and isotretinoin.
The clinical presentation of triglyceride-induced pancreatitis is usually similar to that of pancreatitis from other causes, with epigastric abdominal pain that typically radiates to the back and is associated with nausea and vomiting. However, the course of the disease tends to be more complicated, and the incidence of pancreatic necrosis, abscess formation, sepsis, and organ failure is higher than in pancreatitis from other causes. Physical examination can reveal lipemia retinalis, xanthelasmas, xanthomas over extensor surfaces of the extremities, and hepatomegaly from fatty infiltration of the liver. The serum amylase level can be falsely normal owing to the interference of triglycerides with the assay, and serial dilutions are required to correct it.
Management of triglyceride-induced pancreatitis involves treatment of the acute pancreatitis and lowering the triglyceride levels to < 400 mg/dL. Medications that can contribute to hypertriglyceridemia should be discontinued. Risk stratification of acute pancreatitis should be done early on admission to assess the severity of pancreatitis, using established indexes such as Acute Physiology and Chronic Health Evaluation II (APACHE II), Systemic Inflammatory Response Syndrome (SIRS) criteria, and/or Modified Marshall Score. Initial management of pancreatitis includes supportive measures, with aggressive IV hydration, analgesia, and bowel rest. If the patient has severe pancreatitis and prolonged fasting is expected, pancreatic rest with nasojejunal enteral feeding or total parenteral nutrition should be considered. No guidelines exist to guide the management of acute triglyceride-induced pancreatitis; however, it has been suggested that in patients with severe pancreatitis, additional therapies should be considered on the basis of the current available data.
Insulin activates lipoprotein lipase, leading to enhanced chylomicron and very-low–density lipoprotein (VLDL) metabolism and lowering of serum triglyceride levels, usually by 50%-75% in 2-3 days. Insulin has been used in patients with severe pancreatitis, especially in those with diabetes and concomitant hyperglycemia, although multiple reports have shown that it is also effective in patients who do not have diabetes. Frequent blood glucose checks are required, and dextrose infusion is needed as well to maintain euglycemia. Insulin should be discontinued when the serum triglyceride level is < 500 mg/dL.
In the past, IV heparin was used in combination with insulin because it can cause an initial rise in lipoprotein lipase levels owing to the release of endothelial lipoprotein lipase. This rise is followed, however, by increased degradation by the liver, which leads to lower enzyme levels and chylomicron accumulation, with rebound hypertriglyceridemia. For this reason, heparin should be avoided.
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