Category Archives: Lab Tests

To Test Or Not To Test, That Is The Question: A Patient With Enlargement Of The Thyroid?

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The Question

The other day I got into a discussion with a primary care physician (PCP) about a hypothetical patient.  We had been discussing a case history for an upcoming medical student examination.  The patient was a 40 year old female with a medical history suggesting hypothyroidism.  The physical examination revealed an enlarged thyroid gland.  The question was as follows: what thyroid function studies should be ordered?

The Answer

The PCP said that he would order total thyroxine (TT4), free thyroxine FT4), and thyroid-stimulating hormone (TSH).  I was a bit surprised by his answer and asked if he didn’t also want to order thyroid peroxidase (TPO) antibodies?  He replied something to the effect that in the “real world” docs don’t mess with that kind of stuff.  I became even more surprised and then asked him whether he thought it was important to know what one was treating.  He got a bit hostile and replied that if the TSH were high and the FT4 and TT4 levels low, he would have a diagnosis, primary hypothyroidism.  He explained that the cost of the TPO antibodies (about $50-$80) depending on the laboratory) was not worth the benefit.  My response was “hmmmm.”

What did I really think?

I did not agree with the PCP’s approach to the hypothetical patient but I did not go ballistic since there was some merit to his argument.  On the other hand, it is my opinion that testing for TPO antibodies in the patient described above is worth the modest extra expense.  First of all, as a general principle it is important to know what one is treating.  While primary hypothyroidism is a diagnosis, there are many different causes for the condition and the approach to treatment might well be dictated by the specific etiology.  In those parts of the world where iodine deficiency is not endemic, the most common reason by far for primary hypothyroidism is chronic lymphocytic thyroiditis (CLT) or Hashimoto’s thyroiditis as it is commonly called.  This is an autoimmune disorder which is highly prevalent in females, particularly those over 40 years of age.  As I have discussed in previous entries, the physical examination often offers clues to the diagnosis; in my experience, careful examination of the thyroid gland will reveal a small lymph node on the left, just above the thyroid isthmus.  This node is called a delphian node and its presence means the patient has either CLT or autoimmune hyperthyroidism or Graves disease.  I can’t remember if I have ever had a patient with a delphian node who did not have positive thyroid antibodies.

Anyway, the differential diagnosis of primary hypothyroidism includes CLT, goitrogens (mostly iodine-containing products), familial inborn errors of metabolism (genetic abnormalities of the various steps to synthesis of thyroid hormones or their degradation), gland dysplasia (e.g., hemithyroids), and other rather uncommon entities.  I find thyroid antibodies most helpful when the TSH and FT4 come back normal (I can’t think of any reason to order TT4 but that’s a topic for another time).  The question becomes why is the gland enlarged (here we are assuming that the physician is skilled at telling when a thyroid gland is enlarged rather than there just being a prominent fat ring around the neck)?  It is still likely that the patient has CLT or possibly a so-called simple colloid goiter an entity I don’t understand; I don’t even know if the disorder exists even though almost all textbooks that cover thyroid disorders list it in the differential diagnosis of goiters (a goiter is just another way of describing an enlarged thyroid gland).  If the patient has CLT and enlargement of the thyroid, many endocrinologists will recommend treatment with replacement doses of L-thyroxine to “put the gland at rest.”  There are some data suggesting that such treatment can prevent progressive destruction of the gland which can occur; a number of studies have shown that TPO antibodies are cytotoxic even though most of the inflammation in CLT is lymphocyte-mediated.

So, it’s not so simple deciding what laboratory tests to order or not to order.   I will return to my original argument that whenever possible it’s good to know what specific disorder is being treated with medications, or  maybe, even if the treatment is just observation.  But I can sort of see the PCP’s point of view, sort of.

Interpreting The Results Of Laboratory Studies: Be Careful

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A few weeks ago, I read an interesting piece in the New York Times about errors that a national reference laboratory had made in measuring Vitamin D levels.  Apparently the laboratory had recently discovered (or had been found out?) that for some time it had been reporting erroneous results for serum vitamin D levels, resulting in either falsely high or falsely low values.  The problem was traced to inaccurate standards used in the assay.  Anyway, the report got me to thinking about just how difficult it can be for a patient to have any confidence that a test his doctor orders will provide an accurate result, let alone be interpreted correctly by the doctor.  I do know a little bit about such things given my background as both a clinician who has ordered  lots of laboratory tests and as a former director of a large reference laboratory.

Obstacles to getting an accurate test result

Many patients and health care professionals assume that the mere ordering of a laboratory test is just about all the assurance they need that the test will be performed properly and that the result will provide useful clinical information.  Nothing could be further from the truth.  At every step of the way, from procurement of the specimen, be it blood or urine or whatever, to the actual test report, things can and do go wrong.  For example, if the specimen was supposed to be collected with the patient in the fasting state but the patient had recently eaten, right away the meaning of the test results should be questioned.  If the specimen is not collected, transported, and stored properly before analysis, serious errors can be introduced.  If the assay is not performed properly, the results may be erroneous.  If the standards used to normalize the test results are wrong, the results will be erroneous.  If the normal range used in the test report has been improperly constructed, the test results might be interpreted incorrectly.  If the test results reported for one patient are really those of a different patient, the results will be erroneous.  Finally, if the health professional does get an accurate test result but interprets the result incorrectly, as far as the patient is concerned, it’s almost as bad as an erroneous test result.  In summary, there are many places between the ordering of a test and the reporting of the test result that things might go wrong.

Don’t get me wrong, I believe that most laboratory tests are carried out with great skill and that the results are accurate.  But one should never assume so and wise clinicians know that test results must be interpreted in context; if a test result does not fit with the clinical history, the result should be viewed with suspicion or at least skepticism as to its clinical significance.

Improving the odds that test results will be accurate

There are standard procedures called quality control/quality assurance that all laboratories are supposed to carry out to optimize test results.  These might include running certified standards according to a specified protocol and participating in an external quality assurance program such as those carried out by the College of American of Pathologists or the NGSP (the organization that runs the standardization program for hemoglobin A1c, the test that is widely used in diabetes).  Still, in the end it comes down to the health professional who ordered the test, using clinical judgment to interpret the test result, always reserving the right to question whether the number on the test report fits with the clinical impression.