Brain;

“My patient with severe Crohn’s disease is found to have an elevated serum lipase without other supportive evidence of pancreatitis. What other sources of elevated lipase should I consider?” 

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , Leave a comment

Over 20 different conditions have been linked to elevated serum lipase levels or hyperlipasemia associated with conditions other than pancreatitis. The most common causes are sepsis and acute kidney injury, but less common causes include gastrointestinal bleeding, liver disease, and type 2 diabetes mellitus, and inflammatory bowel disease.1   More specifically, up to 9% of patients with Crohn’s disease may have hyperlipasemia, often associated with a more extensive and active disease.2  

Recall that hyperlipasemia is one of the hallmarks of acute pancreatitis (serum lipase greater than 3-5x the upper limit of normal) but, as noted above, it is not 100% specific for this condition.  Although pancreatic tissue has a 50-to-100-fold greater lipase activity than other organs in the gastrointestinal tract,3 serum amylase may also be elevated in diseases involving salivary glands, stomach, heart, skeletal muscle, white and brown adipose tissue, and even the brain.1 This finding should come as no surprise since, as an enzyme, lipase metabolizes triglycerides into glycerol and free fatty acids and plays a key role in the metabolism and transport of lipids into peripheral tissues. 4   

Last, despite potential extra-pancreatic sources, serum lipase is still preferred over amylase in diagnosing pancreatitis due to its higher specificity and sensitivity. 5  

Bonus Pearl: Did you know that increased intracranial pressure, including intracerebral hemorrhage, edema, and tumors may also be associated with elevated serum lipase levels? 6 

Contributed by Charles Hurth, D.O., Mercy Hospital, St. Louis, Missouri

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References: 

  1. Feher KE, Tornai D, Vitalis Z, Davida L, Sipeki N, Papp M. Non-pancreatic hyperlipasemia: A puzzling clinical entity. World J Gastroenterol. 2024 May 21;30(19):2538-2552. doi: 10.3748/v30.i19.2538. PMID: 38817657; PMCID: PMC11135416. https://pmc.ncbi.nlm.nih.gov/articles/PMC11135416/#B33  
  2. Heikius B, Niemelä S, Lehtola J, Karttunen TJ. Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease. Am J Gastroenterol. 1999 Apr;94(4):1062-9. doi: 10.1111/j.1572-0241.1999.x. PMID: 10201484. https://pubmed.ncbi.nlm.nih.gov/10201484/ 
  3. Tetrault GA. Lipase activity in serum measured with Ektachem is often increased in nonpancreatic disorders. Clin Chem. 1991 Mar;37(3):447-51. PMID: 1706233. https://pubmed.ncbi.nlm.nih.gov/1706233/
  4. Wang H, Eckel RH. Lipoprotein lipase in the brain and nervous system. Annu Rev Nutr. 2012 Aug 21;32:147-60. doi: 10.1146/annurev-nutr-071811-150703. Epub 2012 Apr 23. PMID: 22540257; PMCID: PMC4065112. https://pmc.ncbi.nlm.nih.gov/articles/PMC4065112/
  5. Tenner S, Vege SS, Sheth SG, Sauer B, Yang A, Conwell DL, Yadlapati RH, Gardner TB. American College of Gastroenterology Guidelines: Management of Acute Pancreatitis. Am J Gastroenterol. 2024 Mar 1;119(3):419-437. doi: 10.14309/ajg.0000000000002645. Epub 2023 Nov 7. PMID: 38857482. https://pubmed.ncbi.nlm.nih.gov/38857482/
  6. Larson GM, Koch S, O’Dorisio TM, Osadchey B, McGraw P, Richardson JD. Gastric response to severe head injury. Am J Surg. 1984 Jan;147(1):97-105. doi: 10.1016/0002-9610(84)90041-2. PMID: 6691557. https://pubmed.ncbi.nlm.nih.gov/6691557/

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

“My patient with severe Crohn’s disease is found to have an elevated serum lipase without other supportive evidence of pancreatitis. What other sources of elevated lipase should I consider?” 

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , Leave a comment

Although serum gamma-glutamyl transpeptidase or GGT is a very sensitive test for liver disease, especially of biliary origin, it’s by no means a very specific test. Besides the liver, GGT is found in the kidneys, pancreas, prostate, heart, brain, and seminal vesicles but not in bone (1-4).

 
Obesity, alcohol consumption and drugs are common causes of GGT elevation (2). As early as 1960s, elevated GGT was reported in such seemingly disparate conditions as diabetes mellitus, congestive heart failure, myocardial infarction, nephrotic syndrome and renal neoplasm (3). Nonalcoholic steatohepatitis, viral hepatitis, biliary obstruction, COPD, liver metastasis, drug-induced liver injury can all cause GGT elevation (1-4).

 
An isolated GGT does not necessarily indicate serious or progressive liver disease. That’s one reason it’s often not included in routine “liver panel” lab tests (1).

What to do when GGT is high but other liver panel tests such as ALT, AST, albumin, and bilirubin are normal? If your patient is at risk of acquired liver disease, then further workup may be necessary (eg, hepatitis B and C screening tests). Alcohol consumption should be queried. Don’t forget conditions associated with iron overload. If your patient is obese, diabetic or has elevated both lipids, an ultrasound of the liver to look for fatty liver should be considered. In the absence of risk factors, symptoms, or physical exam suggestive of liver disease, isolated GGT elevation should not require further investigation (1).

 
One good thing that may come out of finding an isolated elevated GGT is to encourage your patient to curb alcohol consumption or lose weight when indicated. But don’t rely on a normal GGT to rule out heavy alcohol consumption as it may miss 70% to 80% of cases (6)! 

 
Bonus Pearl: Did you know that GGT activity is thought to increase in alcohol use due to its role in maintaining intracellular glutathione, an anti-oxidant, at adequate levels to protect cells from oxidative stress caused by alcohol?

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References

1. Carey WD. How should a patient with an isolated GGT elevation be evaluated? Clev Clin J Med 2000;67:315-16. https://www.ncbi.nlm.nih.gov/pubmed/10832186
2. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018;67:6-19. https://gut.bmj.com/content/gutjnl/67/1/6.full.pdf
3. Whitfield JB, Pounder RE, Neale G, et al. Serum gamma-glutamyl transpeptidase activity in liver disease. Gut 1972;13:702-8. https://www.ncbi.nlm.nih.gov/pubmed/4404786
4. Tekin O, Uraldi C, Isik B, et al. Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey. Medscape General Medicine 2004;6(1):e16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140713/
5. Van Beek JHDA, de Moor MHM, Geels LM, et al. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels:evidence for correlated genetic effects. Drug Alcohol Depend 2014;134:99-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909645/

6. Bertholet N, Winter MR, Cheng DM, et al. How accurate are blood (or breath) tests for identifying self-reported heavy drinking among people with alcohol dependence? Alcohol and Alcoholism 2014;49:423-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060735/pdf/agu016.pdf

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?