October 4, 2007

Commentary by Daniel Frenkel, PGY-2 Case: A 46 year old male with diabetes on oral hypoglycemic medications is admitted to the hospital with one day of constant epigastric pain, nausea, vomiting, and an inability to tolerate oral intake. You are concerned about pancreatitis but laboratory analysis reveals amylase levels that are within the normal reference range. You notice that his glucose level is 410mg/dL and that the specimen is described as lactescent. Should you still be concerned about acute pancreatitis? Lactescent or lipemic blood samples are indicative of elevated fatty substances usually in the form of triglycerides. Such samples may interfere with amylase assays and produce false negative results to the extent that acute pancreatitis may actually be the correct diagnosis in a patient with normal amylase levels. While gallstones and alcohol account for roughly 80% of cases of pancreatitis, hypertriglyceridemia is the next most common etiology, accounting for roughly 1-4% ofcases (sometimes noted up to 7%). An association between elevated triglyceride levels and pancreatitis exists where mild to moderate elevations are considered to be an epiphenomenon, while elevations greater than 1,000mg/dL can lead to pancreatitis. Despite the frequency of hypertriglyceridemia causing pancreatitis, it remains unclear how to predict which patients with triglyceride levels greater than 1,000mg/dL will actually develop this disorder. Similar to cholesterol, triglycerides have both exogenous and endogenous sources. When triglycerides are obtained from dietary sources they are initially packaged in chylomicrons while endogenous triglycerides synthesized by the liver are packaged in VLDL. These two lipoproteins are the predominant source of triglycerides in blood and interact with lipoprotein lipase in peripheral tissue in order to store triglycerides in muscle and adipose tissue. Therefore, the development of hypertriglyceridemia is dependent on a balance between thesynthesis and catabolism of these lipoproteins. Primary hypertriglyceridemia is a category of rare hereditary diseases that can cause elevated triglycerides which include Familial Chylomicronemia (Type I Hyperlipidemia), Familial Hypertriglyceridemia (Type IV Hyperlipidemia), and Familial Combined Hyperlipidemia (Type V Hyperlipidemia). Secondary hypertriglyceridemia has numerous common etiologies such as alcohol, diabetes, diet, obesity, estrogen, pregnancy, CRF, hypothyroidism, and drugs (thiazides, beta-blockers, protease inhibitors). The primary hereditary disorders are capable of producing triglyceride levels greater than 1,000mg/dL, while secondary causes require a baseline defect in triglyceride catabolism which is then subjected to the precipitating insult to achieve similar levels. Why do elevated triglycerides cause acute pancreatitis? The exact mechanism is unclear but it is thought to involve increased concentrations of chylomicrons in the blood. Chylomicrons are usuallygeneral management of hypertriglyceridemia… References: 1. Yadav D. and Pitchumoni C.S. “Issues in hyperlipidemic pancreatitis.” Journal of Clinical Gastroenterology. 2003; 36(1): 54-62. 2. Gan S.I., et al. “Hypertriglyceridemia-induced pancreatitis: A case-based review.” World Journal of Gastroenterology. 2006; 12(44): 7197-7202. 3. Kasper D.L., et al. Harrison’s Online: Harrison’s Principles of Internal Medicine, 16th Edition. The McGraw Hill Companies, Inc. 2007, Chapter 335. [www.accessmedicine.com] 4. Alagozlu H., et al. “Heparin and insulin in the treatment of hypertriglyceridemia-induced severe acute pancreatitis.” Digestive Diseases and Sciences. 2006; 51: 931-933.