Laboratory reference ranges can vary depending on the lab, method of assessment, and the health of the population in the area where the reference ranges were established.
Each lab establishes its own reference ranges/intervals, and they are designed to reflect what is typical based on age, gender, and other factors.
Minor discrepancies seen between lab reference ranges can be due to a different standard deviation from the mean used in their sample set. More considerable differences can be due to different analytical methodologies, testing equipment, or even different reagents used by the lab itself. A lab may also cite references established by test manufacturers. Reference populations should be made up of at least 120 subjects and usually reflect the middle 95% of results for that population. It is important to note that disease and dysfunction may be present even when results fall within the conventional or standard range (Testing.com).
Lab discrepancies can be observed when evaluating free testosterone or thyroid antibody studies. Although the units remain the same, the reference intervals used by the major commercial labs Quest and LabCorp can be notably different. For example, Quest calculates free testosterone based on total testosterone, SHBG, and albumin and reports in pg/mL. LabCorp also reports in pg/mL but uses a direct, analog immunoassay method with a distinctly different reference range than Quest. Reference ranges for thyroid antibodies also differ significantly between Quest and LabCorp.
Regarding evaluating lipase values, reference ranges can vary from lab to lab:
- Quest 7-60 U/L
- LabCorp 18-71 yrs 14-85 U/L
Textbook guidelines provide a wider range, e.g., 0-160 U/L (Pagana 2021), while labs in different countries may have even wider ranges. The ODX optimal range for lipase is narrower at 22 – 51 U/L in order to identify and track trends over time. Both pancreatic and non-pancreatic causes of elevated lipase should be investigated, including inflammatory bowel disease, celiac disease, liver cirrhosis, cholecystitis, and organ damage (Hameed 2015). Low levels of lipase should also be monitored as they can be associated with metabolic disorders, including obesity and metabolic syndrome (Ko 2020, Oh 2020).
Values of concern should be repeated, monitored over time, and interpreted within the context of an individual’s lifestyle, symptomatology, medical history, and even family history.
Below is an overview of the determination and shortcomings of standard reference ranges.
Laboratory reference ranges, also referred to as “reference intervals,” are primarily determined by a direct approach that uses specimen samples from a statistically significant preselected reference population that is usually determined to be free of specific diseases or conditions. Reference intervals are based on a distribution of test values and are not the same as clinical decision limits, which are more individualized to each clinical case (Jones 2018).
The same notion is applied to functional blood chemistry, which focuses on trends outside of optimal range as well as a comprehensive picture of an individual’s history, lifestyle, and nutrition status. It is important to remember that “normal or average” does not necessarily mean healthy (Ceriotti 2008). Optimal ranges can help identify early changes in biochemistry and physiology that can translate into dysfunction down the road.
In general, standard reference intervals (Merck, Katayev 2010, Lamers 2019, Costello 2016):
- Represent normal distribution of results but not necessarily normal physiological function
- Reflect a wide range of values for 95% of individuals presumed to be healthy
- Do not necessarily correlate with clinical outcomes
- Can vary from lab to lab due to differences in testing equipment, technique, geographic area, etc.
- Reflect population averages in the vicinity of the testing laboratory, and reflect the increasing prevalence of disease and dysfunction in that local population
- Only detect overt pathology once the “damage is done”
- Fail to highlight or reveal subclinical imbalances or metabolic issues
- “Lab test results in some people with disease fall within the reference range, especially in the early stages of a disease” (American Association of Clinical Chemistry)
References
Ceriotti, Ferruccio, and Joseph Henny. “"Are my Laboratory Results Normal?" Considerations to be Made Concerning Reference Intervals and Decision Limits.” EJIFCC vol. 19,2 106-14. 16 Oct. 2008
Costello, Rebecca B et al. “Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.” Advances in nutrition (Bethesda, Md.) vol. 7,6 977-993. 15 Nov. 2016, doi:10.3945/an.116.012765
Hameed, Ahmer M et al. “Significant elevations of serum lipase not caused by pancreatitis: a systematic review.” HPB : the official journal of the International Hepato Pancreato Biliary Association vol. 17,2 (2015): 99-112. doi:10.1111/hpb.12277
Jones, Graham R D et al. “Indirect methods for reference interval determination - review and recommendations.” Clinical chemistry and laboratory medicine vol. 57,1 (2018): 20-29. doi:10.1515/cclm-2018-0073
Katayev, Alex et al. “Establishing reference intervals for clinical laboratory test results: is there a better way?.” American journal of clinical pathology vol. 133,2 (2010): 180-6. doi:10.1309/AJCPN5BMTSF1CDYP
Ko, Juyeon et al. “Low serum amylase, lipase, and trypsin as biomarkers of metabolic disorders: A systematic review and meta-analysis.” Diabetes research and clinical practice vol. 159 (2020): 107974. doi:10.1016/j.diabres.2019.107974
LabCorp Free Testosterone https://www.labcorp.com/tests/144980/testosterone-free-direct. Thyroid Antibodies https://files.labcorp.com/testmenu-d8/sample_reports/006684.pdf
Lipase https://www.labcorp.com/tests/001404/lipase
Lamers, Yvonne. “Approaches to improving micronutrient status assessment at the population level.” The Proceedings of the Nutrition Society vol. 78,2 (2019): 170-176. doi:10.1017/S0029665118002781
Merck Manual Professional Version. Normal Laboratory Values. https://www.merckmanuals.com/professional/resources/normal-laboratory-values/normal-laboratory-values
NIH. What are blood tests.? https://www.nhlbi.nih.gov/health/blood-tests
Oh, Hyoung-Chul et al. “Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis.” Gut and liver vol. 11,6 (2017): 878-883. doi:10.5009/gnl17066
ODX Research Blog. Enzyme Biomarkers: Pancreatic Lipase https://www.optimaldx.com/research-blog/enzyme-biomarkers-pancreatic-lipase
Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.
Quest Diagnostics Free Testosterone. https://testdirectory.questdiagnostics.com/test/test-detail/18944/testosterone-free?cc=MASTER
Thyroid antibodies https://testdirectory.questdiagnostics.com/test/test-detail/7260/thyroid-peroxidase-and-thyroglobulin-antibodies?cc=MASTER
Lipase https://testdirectory.questdiagnostics.com/test/test-detail/606/lipase?cc=MASTER
Testing.com formerly American Association for Clinical Chemists Lab Tests Online. Reference Ranges and What They Mean. https://www.testing.com/articles/laboratory-test-reference-ranges/