What constitutes a normal test result?

From Dr. Lewis Blevins.  What constitutes a normal test result? In most endocrine assays, it is a population of supposedly normal individuals that defines the upper and lower limits of normal. Take the mean, and 1.96 standard deviations above and below the mean…there you have it! It’s not that simple but it is…really. Of course, some tests, such as IGF-1, have age and sex-matched normal ranges. Here is the difficulty for physicians…and patients…..some normal people, about 5%, have abnormal values but are truly normal and do not have a particular disease. And, some people have disease but have normal laboratory values! Fortunately, we have confirmatory tests. Take, for example, the person who has an elevated IGF-1 value and no clinical stigmata of acromegaly…and the patient with a normal IGF-1 value and fairly convincing evidence for acromegaly on history and exam. How do we sort it out? In this instance we do an oral glucose suppression test as normal people suppress GH in response to glucose but people with acromegaly will not. Of course, MRI is also useful. The point is, clinical index of suspicion matters…and confirmatory tests are often required. One other important thing to keep in mind is that normal is relative. Everyone has his or her set point for hormone levels.

In the case of Free T4, for example, there is a bell shaped curve of distribution with a mean and 1.96 SD below and above defining the normal range. Each one of us will have, on repeated measures, a Free T4 level that will cluster in an area of the normal range defining what is normal for us. We each have our own little bell shaped curve and normal limits. The problem is that, if one has pituitary disease, we do not know where “your” normal level sits. So, determining the adequacy of a dose of thyroid hormone replacement, for example, depends on trial and error with good old fashioned assessments as to how you’re doing coupled with lab tests.

How does this translate? Well. A doctor might tell you your levels are “fine” but you may feel hypothyroid. If your levels are in the lower half of the normal range then perhaps an increase in the dose is warranted as maybe your set point, or where you belong, is in the upper half of the normal range. Conversely, patients in the upper half of the normal range who feel hyperthyroid probably require a dose adjustment downwards to feel well. One thing is for sure, you should not take excessive amounts of thyroid hormone in your quest to feel well if your levels are close to or above the normal range. That is simply too risky for lots of different reasons.

I believe in dose optimization…and so should you. GH, thyroid hormone, androgens, estrogens…these are all hormone replacements that can be adjusted to optimize levels within the normal range. Conversely, IGF-1 levels can be nailed in acromegaly, and thyroid hormone levels in TSH adenomas, to improve sense of well being and “normalize levels for that particular individual. Prolactin is a different story. Cortisol levels are easy in Cushing’s…not so much in adrenal insufficiency.

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