Impaired Risk Review…When Normal Laboratory Results Aren’t Truly Normal

Most blood test results come back from the laboratory with a measured value and a reference range next to it. The reference range is supposedly the “normal” range of values for the population being tested. The range is wide (after all, normal is relative) from a low end of the scale to an upper limit.

 There are times, though, when normal truly isn’t—when the value is in range, but represents a change from prior measurements or a proportion relative to another value that makes it indicative of a problem.

Kidney function testing is one example. Generally, besides a urine specimen, the serum measurements for kidney function are creatinine and blood urea nitrogen.
Creatinine, the more sensitive one, has a range of approximately 0.8-1.6 mg/dl. A value of 1.6 may fall within that range, but if the value had been 1.3 six months before and 1.0 the previous year, this could be indicative of impending or insidious renal failure. The next value may be far outside the reference range, but it could have been easy to see coming, despite being a “normal” value.
PSA, or prostate specific antigen, is another one where one value doesn’t tell the whole tale. Normal value on PSA is between 0.0 and 4.0 ng/ml. A 3.5 may be highly abnormal when it follows a reading of 1.6. An isolated abnormal PSA value can be a predictor of prostate cancer when it’s doubling time is short or the rate of the rise of PSA (PSA velocity) is high. Each time, this normal value really isn’t normal relative to its predecessor.
Another instance is after treatment for prostate cancer. After a radical prostatectomy (removal of the gland by surgery), the PSA level should be very close to zero, if not exactly that. A well within normal range number of 2, for instance, can be proof that the cancer was not fully eradicated and there is a recurrence of the disease.
Cholesterol levels are the subject of both wide normal ranges and controversy. Older reference ranges have an upper level of cholesterol of as much as 260 mg/dl. However, the American Heart Association, as well as the American Diabetes Association, would prefer levels south of 200 mg/dl, and even under 160. In addition, as cholesterol has both good (HDL) and bad (LDL) fractions, a “normal” cholesterol of 190 may not be normal if the good fraction is only a small percentage of it. That, too, would be grounds for medical treatment.
One more example of normal values raising red flags is in tests where the proportion of one value to another is not as expected. Total proteins, one of the insurance tests run routinely and usually present in comprehensive metabolic panels run by medical practitioners, measures the total amount of proteins in the blood plasma. Proteins are important building blocks of cells and tissues, and they are important as measurements of good health and body regulatory functions.
There are two types of proteins—albumin and globulin—found in the blood. Albumin is a carrier of small molecules and keeps fluid regulation in blood vessels orderly. Globulins have enzymes, antibodies for fighting disease, and other proteins. Normally, albumin levels are about 3.5 to 5.5 g/dl and globulins 2.1 to 3.9 g/dl. The ratio of albumin to globulin is around one and a half to two times, with albumin the higher absolute value.
What happens when albumin is 3.6 and globulin is 3.9? Both are normal values on the reference range, but an inverted albumin to globulin ratio (in this case a fraction less than one) can indicate underlying cancer, immune system deficiencies, intestinal, kidney or liver disease. It would have to be looked into much more closely than a “normal” set of values would indicate.
Normal is certainly relative.Normal laboratory values are what we all hope for, but ironically, some are more normal than others.

Robert Goldstone for March 2012 issue of Broker World Magazine. Author’s Bio Robert  Goldstone, MD, FACE, FLMI Goldstone, board certified internist and endocrinologist, is vice president and chief medical officer for Pacific Life and Pacific Life and Annuity.

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