What Does “Normal” Really Mean in Lab Results?

What "Normal" Really Means: Understanding Lab Reference Ranges | Diagnostic Equity

Deandra White: Hello, I'm Deandra White with Diagnostic Equity, and today we're exploring something that confuses patients everywhere, and that's why normal lab results can differ from one lab to another. That's right, your test results might look different depending on where you go, even if nothing about your health has changed at all. So what's really going on with that?

We're joined here by Dr. Sarah Bergbower, a doctor of clinical laboratory science, to break down how reference ranges are set, why they vary across labs, and how factors like age, sex, ethnicity, and even your local population, how that data can influence what's considered normal. So whether you're a patient comparing results online or a provider trying to interpret trends, this conversation will help you understand what normal really means, and how to avoid misreading your own results.

How Reference Ranges Are Established

Deandra White: So my first question for you is that most patients assume that reference ranges are universal, but we both know that's not true, so can you explain what reference ranges really mean and how they're established?

Dr. Sarah Bergbower: Sure, and this is a really great place to start. There are a few ways that reference intervals may be established. One is that the laboratory will create their own reference intervals based on the statistical analysis of the central 95% of the population, and that population is likely to be local, perhaps regional to the laboratory, but the idea here is that the results are representative of the area. And that reference population must therefore be carefully selected according to the clinical basis of the test of interest.

A laboratory may also choose to adopt published reference intervals, which may be found in the scientific literature, or it may be available directly through the assay manufacturer. Finally, labs may use consensus reference intervals that are determined by an association of medical experts that perhaps were likely set within a specific group or with a disease in mind, and this is backed by large clinical studies.

Of course, there's going to be advantages and disadvantages to choosing to establish any of these methods. But I do want to emphasize that the basis for these methods is indeed based on statistics. Samples are taken from individuals who are apparently healthy. Then the values or results from these samples for that particular test are arranged into a graph, and they produce a Gaussian curve, or a normal distribution, and it's a bell-shaped curve, where we expect most of the values to cluster around the average value in the middle, where there are fewer values on the upper and lower extremes. The reference interval is then established where the upper and lower 2.5% of the results, which corresponds to two standard deviations from the mean, these are then excluded from the range. Sometimes one-sided intervals are established for the test, where one extreme is not clinically relevant, so in that case, we'll have 5% total that's used for range exclusion of those tests.

Deandra White: What would be the reasoning between using a smaller reference range for a particular community, and saying, at this lab, we want to use this smaller range, versus using something on a national scale?

Dr. Sarah Bergbower: So, there are some factors that will influence how that test may be performed, or performing within a population. So, sometimes it's of clinical interest to capture that within the particular population. For example, if you have someone who is from areas of the country where there's high altitude, the fact that they live in that location might alter some of the physiological processes in their body that would perhaps contribute to differing results. So when you take that and compare it to a standardized range that doesn't account for that, you may have some differing values.

Deandra White: That's a really good example. I never thought about that, like, living in Denver or something versus living in Florida, and how that could change your labs.

Dr. Sarah Bergbower: Right. Yeah, hemoglobin is where my mind went.

How Age, Sex, Ethnicity, and Local Population Affect What's "Normal"

Deandra White: And how can differences in age, sex, ethnicity, or even the local population affect what's considered normal?

Dr. Sarah Bergbower: Great question, because they really do. Essentially, ranges are for comparing yourself to most of the population. So, therefore, special considerations are going to be required for evaluating specific subpopulations, such as by age, because infants and children, adults, the elderly, these are all going to have differing normal values from each other than just comparing to a typical healthy adult. Sex and race may also affect reference interval interpretations, too.

A prominent example of this is the estimated glomerular filtration rate, or GFR, because it is influenced by all of the above. It naturally declines with age, it's affected by pregnancy and muscle mass, and it has historically included race in its calculation. The eGFR is used to assess kidney health. African Americans typically have higher eGFRs, which at first sounds like a good thing, because anything greater than 90 indicates healthy functioning. But the problem is that since African Americans have a different scoring for comparison amid greater risks, this actually led to delays in treatment.

For more examples, we know that the absolute neutrophil count, or ANC, is influenced by genetics, and that has not been appropriately represented in reference intervals. Liver enzyme reference ranges have been influenced by early stages of asymptomatic disease that we didn't recognize was there. So, yes, because there are multiple variables that do affect the population, both seen and unseen, these will also affect the reference ranges used for their comparisons.

Deandra White: And how would patients know when, let's say for eGFR, how would an African American patient know which version of the eGFR to pay attention to, and how to use that to determine where to go from here?

Dr. Sarah Bergbower: This is where it's important to speak with your provider to make sure that some of these calculations are not accounting for that. With the eGFR specifically, race was actually removed from the calculation in 2021, so that's no longer the case.

Deandra White: Yes, thank you. I just wanted to reference that because eGFR is a big topic when it comes to ethnicity and how that's being calculated, and how it influences the way providers look at patients' results and treat them from there on.

Common Pitfalls When Comparing Results Across Labs

Deandra White: My next question is, what are some common pitfalls when patients compare lab test results from different labs?

Dr. Sarah Bergbower: One of the most common pitfalls involves the interpretation of borderline values. That value may fall within the reference range if it's resulted from one lab, but maybe outside the range for another lab. And this is where context is important. The question is, how do we interpret this value appropriately, and does it make sense within the clinical picture?

Are values dependent upon the specimen sample type collected? Was the sample collected at the correct time? Does fasting status influence the measurements? Were there other underlying conditions? Was there an interference from medication? Was the sample transported or stored correctly? Any of these pre-analytical variables can influence the direction of the result. So, if the value is still borderline, and even if it's not, clinical correlation with history and presentation should help make sense of the result. Has it been trending? Or is it markedly different than what it was? What could cause this, and is that what's likely taking place?

Another pitfall is to assume that the same specific methods or analyzers are being used at both labs for measurements, and that could also account for differences in their reference ranges. That would be a good lab test question for your ordering provider: to what extent may my results change depending on testing methodology between two laboratories? It may be more convenient for consistency to have lab results coming from the same laboratory, if possible.

Deandra White: That's helpful, and I think it's also very helpful to mention that looking at trends is really going to be the determining factor of whether there's actually something wrong, or something outside of your normal as a patient.

Consistency, Expertise, and What Lab Professionals Actually Do

Deandra White: Dr. Bergbower, for patients tracking their labs over time, what should they know about consistency, especially if results come from multiple facilities?

Dr. Sarah Bergbower: Medical laboratory professionals are highly trained to ensure consistency in lab testing. It's literally within their job description as quality assurance. These professionals do frequent analyzer preventative maintenance, calibration, and quality control on a regular basis, and they know how to look for deviations. They are capable of recognizing pre-analytical, analytical, and post-analytical errors, and they know the steps to both avoid them and fix them. When you have results coming from one lab, you can be sure of consistency.

Now, results could possibly appear to be inconsistent when they are compared across multiple facilities, because there could be underlying differences in the methodology and how the analyte is detected and measured. Some laboratories may also differ in what they actually report. For example, some laboratories don't report trichomonas or sperm in routine urinalyses, while others do. Some differ in how they identify reactive or atypical lymphocytes, and banded or immature neutrophils, which are manually performed.

Deandra White: And Dr. Bergbower, medical laboratory scientists such as yourself do much more than just run tests — they help determine what's normal for different patients. Can you explain how your expertise guides the interpretation of lab test results for patients?

Dr. Sarah Bergbower: Sure, so when you establish care with a provider and develop a testing history, we can trend your results and look for a delta, which is a significant change that occurs outside of your ordinary. From there, we begin a quick investigation to find out why, and we'll double check that the specimen met all of the pre-analytical requirements — that it wasn't hemolyzed, that it was stabilized correctly, all of those things. We'll even recheck the value, and we'll make sure that the value makes sense in the context of history and presentation.

Deandra White: And how would you be integrated into, let's say, the exam room, if something were abnormal, or if you caught something? How could that communication be implemented?

Dr. Sarah Bergbower: Anytime that a medical laboratory professional sees that something is not quite right with a result — if the specimen is perhaps hemolyzed, or if it is an unusual color, because that does happen — there will often be a note that appears on the lab test report so that the provider can use that information to make their decision-making a little bit more informed, noting that perhaps the reason the result looks like this is because it was influenced by another factor found upon investigation.

Deandra White: Okay, that's very helpful, because it's so hard for patients to see how important your jobs are when you're not immediately patient-facing in the exam room, but that's a good way to have that communication with the provider about what's really going on with the labs, and helping them to make a better-informed decision with their patient.

Dr. Sarah Bergbower: And with that being said, it's not unusual to receive a phone call from a provider asking about why a patient's specific gravity is 1.030 — really, really high — when they haven't had this before. The medical laboratory professional can ask, well, did they have some imaging studies done recently? Because that is going to influence the specific gravity of their urinalysis. So, conversations between providers and the laboratory do happen, and they are helpful.

How the Diagnostic Equity Platform Empowers Patients

Deandra White: You are also helping answer questions for patients on the Diagnostic Equity platform. Can you share how that work helps patients better understand their lab results and make sense of what's normal to them?

Dr. Sarah Bergbower: Yes, so anyone can submit questions to lab experts who are real people, and we can educate on some of the factors that go into making sense of the lab test result. We can explain why a result may have had a particular value, and provide suggestions on further testing to discuss with your provider.

I'll highlight an example. There was a question submitted by someone seeking to explain recurrent joint pain. When they revealed they had a family history of gout and autoimmune diseases, the medical laboratory professional noticed that among the supplements they had listed, these were known to cause joint pain by increasing uric acid levels. But gout wasn't likely, and those uric acid levels that were measured were within the normal range. At the same time, although preliminary testing for rheumatoid arthritis was negative, the patient did not have anti-CCP testing performed, which the laboratory professional was able to recommend as the preferred test indicated in the literature, especially in light of the patient's autoimmune medical history.

Deandra White: Oh my gosh, that's so cool.

So what would you say is the most important thing patients can take away from our conversation today about reference ranges, and what normal really means?

Dr. Sarah Bergbower: Essentially, ranges are for comparing yourself to most of the regional population — the normal distribution. Values within the ranges don't always indicate the absence of a disease, and values outside of the ranges don't always indicate the presence of a disease. Medicine is meant to be personalized. So, urge your provider to clinically correlate with your specific medical history and presentation.

Deandra White: Thank you so much. That was a very insightful conversation with Dr. Bergbower about what normal really means when it comes to your lab results.

If there is one takeaway, it's this: your numbers only make sense in context. Reference ranges aren't one-size-fits-all — they reflect your lab's methods, their instruments, and the population they're serving. If you ever feel unsure about your results or how they were interpreted, remember, you can ask questions.

Visit DiagnosticEquity.org to connect with certified medical laboratory scientists, such as Dr. Bergbower, and get clear, expert answers about your lab tests. I'm Deandra White, and this has been Diagnostic Equity, brought to you by Diverse Health Hub, where we're bridging the gap between lab science and real-world understanding. Thank you for tuning in, and we'll see you next time.

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