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

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.

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