The "Normal" or Reference Range
"Your test was out of the normal range," your doctor says to you, handing you a sheet of paper with a set of test results, numbers on a page. Your heart starts to race in fear that you are really sick. But what does this statement mean, "Out of the normal range"? Is it cause for concern? The brief answer is that a result out of the normal or reference range is a signal that further investigation is needed.
The term "normal range" is not used very much today because it is considered to be misleading. If a patient's results are outside the range for that test, it does not automatically mean that the result is abnormal. Therefore, today "reference range" or "reference values" are considered the more appropriate terms, for reasons explained on the next page. The term reference values is increasing in use and is often used interchangeably with reference range. For simplicity, we use the term reference range in this article.
Tests results—all medical data—can only be understood once all the pieces are together. Take one of the simplest medical indicators of all—your heart rate. You can take your resting heart rate right now by putting your fingers on your pulse and counting for a minute. Most people know that the "average" heart rate is about 70 beats per minute. How do you know what a "normal" heart rate is? We know this on the basis of taking the pulse rate of millions of people over time.
You probably also know that if you are a regular runner or are otherwise in good physical condition, your pulse rate could be considerably lower—so a pulse rate of 55 could also be "normal." Say you walk up a hill—your heart rate is now 120 beats a minute. That would be high for a resting heart rate but "normal" for the rate during this kind of activity.
Your heart rate, like any medical observation, must be considered in context. Without the proper context, any observation or test result is meaningless. To understand what is normal for you, your doctor must know what is normal for most other people of your age and what you were doing at the time—or just before—the test or observation was conducted.
The interpretation of any clinical laboratory test must consider this important concept when comparing the patient's results to the test's "reference range."
What is a reference range?
Some tests provide a simple yes or no answer. Was the culture positive for strep throat? Did the test find antibodies to a virus that indicates an infection?But for many more tests, the meaning of the results depends on their context. A typical lab report will provide your results followed by a reference range. For example, your results for a thyroid-stimulating hormone (TSH) test might look something like: 2.0 mIU/L, ref range 0.5 – 5.0 mIU/L. The test results indicate that it falls within the reference range.
How was that reference range established? The short answer is: by testing a large number of healthy people and observing what appears to be "normal" for them.
The first step in determining a given reference range is to define the population to which the reference range will apply, for example, healthy females between 20 and 30 years old. A large number of individuals from this category would be tested for a specific laboratory test. The results would be averaged and a range (plus or minus 2 standard deviations of the average) of normal values would be established.
The term "reference range" is preferred over "normal range" because the reference population can be clearly defined. Rather than implying that the test results are being compared with some ill-defined concept of "normal," the reference range means the results are being considered in the most relevant context. When you examine test results from different populations, you quickly discover that what is "normal" for one group is not necessarily normal for another group. For example, pregnancy changes many aspects of the body's chemistry, so pregnant women have their own set of reference ranges.
Effects of Age and Sex
For many tests, there is no single reference range that applies to everyone because the tests performed may be affected by the age and sex of the patient, as well as many other considerations. Some examples of variation in reference ranges based on age:- Alkaline phosphatase is an enzyme found in the cells that make bone, so its concentration in the body rises in proportion to new bone cell production. In a child or adolescent, a high alkaline phosphatase level is not only normal but desirable—the child should be growing healthy bones. But these same levels found in an adult are a sign of trouble—osteoporosis, metastatic bone disease (extra bone growth associated with tumors), or other conditions. It is because of these significant variations due to age that the few reference ranges that you may see on this site do not include ranges for children or adolescents. Experience from testing large numbers of people has led to different reference ranges by age group.
- Hemoglobin and hematocrit (a red blood cell measure) both decline as a natural part of the aging process.
- Creatinine is produced as a natural by-product of muscle activity and is removed from your bloodstream by your kidneys. Creatinine levels will be affected by a person's muscle mass as well as their kidney function. It is often measured as a gauge of how well your kidneys are functioning. Because males have greater muscle mass than females, the reference range for males is higher than for females.
- The enzyme creatine kinase (CK) and one of its forms called CK-MB present a similar situation. CK is released into the bloodstream by damaged muscles; CK-MB is released into the bloodstream when the heart muscle is damaged. Therefore, a high level of CK-MB indicates damage to the heart muscle, so this enzyme is one of the indicators used to diagnose heart attacks. Because of their greater muscle mass, men tend to have higher CK levels and the level of CK-MB that indicates a heart attack in men is higher than for women. When the test first came into use, the reference range was based on the higher levels. Many elderly women being tested for a heart attack demonstrated considerably lower levels of CK-MB (because of their smaller muscle mass) and, thus, did not pass the threshold level believed to indicate a heart attack; so heart attacks were often missed in these women.
Other Factors Affecting Test Results
Laboratories will generally report your test results accompanied by a reference range keyed to your age and sex, if appropriate. Your physician then will still need to interpret the results based on personal knowledge of your health status, including any medications or herbal remedies you may be taking. A plethora of additional factors can affect your test results: your intake of caffeine, tobacco, alcohol, and vitamin C; your diet (vegetarian vs. carnivorous); stress or anxiety; or a pregnancy. Even your posture when the sample is taken can affect some results, as can recent heavy exertion. For example, albumin and calcium levels may increase when shifting from lying down to an upright position.Factors such as occupation, altitude, and distance from the ocean have been known to affect results. Regular exercise can also affect values of certain tests; in particular, levels of creatine phosphokinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) will increase. Additionally, testosterone, luteinizing hormone (LH), and platelet levels can increase in people who participate for months and years in strenuous exercise such as distance running and weightlifting.
All these considerations underscore the significance of taking blood or urine samples in a standardized fashion for performing and interpreting laboratory tests (and home tests as well). It is important to comply with your doctor's instructions in preparing for the test, such as coming in first thing in the morning, before you eat anything, to get your blood drawn. That compliance makes your sample as close as possible to others; it keeps you within the parameters of your reference group.
When "Normal" Doesn't Matter
For some tests, such as cholesterol, rather than worry about the reference range, the vast majority of people need only be concerned if their test result falls above or below a cut-off value that is sometimes referred to as a "decision point". If, for example, as studies have shown, a cholesterol level of 200 milligrams per deciliter is the cut-off where heart disease risk should trigger medical intervention, then it doesn't really matter if this result falls into a statistically "normal" range.There are additional tests for which the "normal" range is irrelevant. In testing for the amount of a drug in the blood of an unconscious person, for example, the doctor will interpret the result in terms of the likely effects of the drug at the detected level, not in terms of a reference range.
In addition, clinically significant, dramatic changes in a person's test values, even if those values remain within the reference range for that test, should be brought to the doctor's attention.
What does it mean if my test result is out of the reference range?
First, there are a few reasons why a test result could fall outside of the established reference range despite the fact that you are in good health:- Statistical variability: Even when performing the same test on the same sample multiple times, 1 out of 20 (or 5%) determinations will fall outside an established range, based on the laws of probability. Sometimes, if the test is repeated on this same sample, the result will then be within range.
- Biological variability: If a doctor runs the same test on you on several different occasions, there's a good chance that one result will fall outside a reference range even though you are in good health. For biological reasons, your values can vary from day to day. That is why a doctor may repeat a test on you and why he may look at results from prior times when you had the same test performed.
- Individual variability: References ranges are usually established by collecting results from a large population and determining from the data an expected average (mean) result and expected differences from that average (standard deviation). There are individuals who are healthy but whose tests results, which are normal for them, do not always fall within the expected range of the overall population.
However, a result outside the range may indicate a problem and warrant further investigation. Your doctor will evaluate your test results in the context of your medical history, physical examination, and other relevant factors to determine whether a result that falls outside of the reference range means something significant for you. He may reorder the test. Perhaps the analyte being measured happened to be high that day due to one of the reasons stated previously or perhaps something went awry with the sample (the blood specimen was not refrigerated, or the serum was not separated from the red cells, or it was exposed to heat). Your doctor may also compare the latest test result to previous results if you have been tested for the same thing in the past to get a better idea of what is normal for you.
Laboratories will generally report the findings based on age and sex when appropriate and leave it to the physician to interpret the results based on factors such as diet, your level of activity, or medications you are taking. If you have a result that falls outside the reference range, talk to your doctor about what it means for you and what steps need to be taken next.
If you know of any special circumstances that could affect a test, mention them to your doctor; don't assume your doctor has thought of every possible circumstance.
Why are so few reference ranges included on this web site?
With all this talk of reference ranges, you may notice that few of the test descriptions on this web site include the reference range. There are several reasons for this:
- In general, reference ranges are specific to the laboratory that produces the test results. For many analytes, different laboratories use different kinds of equipment and different kinds of testing methods. This means that each laboratory must establish its own reference ranges using data from its own equipment and methods. The laboratory must supply your test result with an accompanying reference range on the laboratory report. Consequently, there is no such thing as a standard reference range. Of course, each test does have a theoretical reference range that we could include on this site, which can be found in many books and other online sources, but it may have little diagnostic meaning for you. You and your doctor should apply the reference range supplied by the laboratory performing the test. That being the case, however, for a few specific tests, such as the electrolytes, there is a high degree of consistency if not standardization, among clinical laboratories in the methodologies and procedures used for these particular tests. These laboratory methods have been in use for many years now so their reference ranges have been well-established and typically reflect numbers that are very similar to the theoretical reference range. Because of this greatly reduced variability in the reference ranges for these select number of tests, their reference ranges are included on this site. The source of the range for each test is Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, a well-respected and authoritative textbook on the subject that is used by medical professionals.
- You may notice that the few select reference ranges listed here are specific for adults only and there are no ranges included for children or adolescents. The reason is that from infancy throughadolescence, a child's body goes through many changes and growing cycles. Several things that are tested in a laboratory such as chemical levels, hormones, etc. vary greatly as a child goes through the different growth stages. The laboratory where your child's sample is tested has established reference ranges for the different stages of child development. Theoretical reference ranges exist for children, but they are numerous and do not lend themselves to easy interpretation, so they are not included on this site. The best source of information regarding your child's lab test results is your child's doctor.
- For a few other analytes, such as cholesterol, glucose, and prostate specific antigen, there has been a major effort to standardize the laboratory test methods and report formats. The result has been the establishment of a set of cut-off numbers that are different from reference ranges in that they reflect clinical decision points rather than a statistically "normal" range. We have included the published targets in our discussions of these few tests.
- We want you to be informed, but we don't pretend to take the place of communication with your doctor. We want you to understand what the test is for, but because we can't be aware of all the factors that could affect your test results, we can’t interpret the results without more information. If you need further explanation of your results, you should talk to your doctor. This remains true even for those tests, such as the components of the basic metabolic panel (BMP), for which we have included reference ranges. Remember, a reference range is merely a guide for your doctor. He or she will interpret the result in the context of your medical history and current presentation – something that no web site is yet able to do.
Common Misconceptions
There are two main misconceptions about test results and reference ranges:Myth: "An abnormal test result is a sign of a real problem."
Truth: A test result outside the reference range may or may not indicate a problem—the only sure signal it sends is that your doctor should investigate it further. You can have an abnormal value and have nothing wrong—but your doctor should try to determine the cause.
It's possible that your result falls in that 5% of healthy people who fall outside the statistical reference range. In addition, there are many things that could throw off a test without indicating a major problem: High blood sugar could be diet-related rather than caused by diabetes. A lipid result could be high because you didn't fast before the test. High liver enzymes can be the temporary result of a recent drinking binge rather than a sign of cirrhosis. New drugs come on the market constantly, faster than laboratories can evaluate whether they might interfere with test results. It is not uncommon for many of these drugs to interfere with certain laboratory tests, resulting in falsely high or low values.
Most likely, your doctor will want to rerun the test. Some abnormal results may disappear on their own, especially if they are on the border of the reference range. Your doctor will also seek explanations for an abnormal result, such as those above. A key point your doctor will address is, how far out of the reference range is the result?
If these investigations point to a problem, then your doctor will address it. But there are very few medical questions that can be answered by a single test.
Myth: "If all my test results are normal, I have nothing to worry about."
Truth: It's certainly a good sign, but it's only one set of tests, not a guarantee. There is a large overlap among results from healthy people and those with diseases, so there is still a small chance that there is an undetected problem. Just as some healthy people's results fall outside the reference range, lab test results in some people with disease fall within the reference range.
If you're trying to follow a healthy lifestyle, take it as a good sign, and keep it up. But if you're engaging in high-risk behavior, such as drug and alcohol abuse or a poor diet, it only means "so far so good," and the potential consequences haven't caught up with you yet. A good test result is not a license for an unhealthy lifestyle.
If you had abnormal results previously, normal results certainly provide good news. But your doctor may want to conduct follow-up tests some months later to make sure you're still on track and to document any trends.
Article Sources
Link Source Here...
Internet:
National Cholesterol Education Program website, available online through http://www.nhlbi.nih.gov
Cornell University Veterinary School website, available online through http://web.vet.cornell.edu
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