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CommentaryAlpert's EditorialsDon't React to Symptoms in Patients with Subclinical Hypothyroid Disease

Don’t React to Symptoms in Patients with Subclinical Hypothyroid Disease

Many years ago, when we were in training, it was commonly taught on rounds that patients with either hypothyroidism or hyperthyroidism might not have a clear history or clinical signs and symptoms suggesting their underlying condition. Thus, we were taught that one should have a low threshold for ordering thyroid function blood tests. Although the pattern of a low thyroxine and an elevated thyroid stimulating hormone (TSH) fit our understanding of pathophysiology, a conundrum arose regarding the pattern of a normal thyroxine level in the setting of an elevated TSH, a condition that came to be known as “subclinical hypothyroidism.” Was the pituitary an early warning system that could detect an abnormality before there were any clinical sequelae, or was it overly sensitive and not indicative of a disease state that warranted therapy?

What makes the clinical situation particularly difficult is that many patients with subclinical hypothyroidism have become convinced that they are symptomatic because of a deficiency in thyroid hormone and that they would benefit from thyroid replacement therapy. The idea that they are truly deficient in thyroid hormone is often based on the presence of symptoms such as fatigue, cold intolerance, dry skin, dyspnea, hair loss, constipation, mood lability, and poor concentration that “must” be due to a thyroid problem, despite repeated explanations to the contrary by 1 or more physicians. Was the “subclinical” part of hypothyroidism the result of a quiet and subtle call from the pituitary or from our deafness to the condition?

In this issue of The American Journal of Medicine, Carlé et al1 from Denmark report on results obtained from 3 large cross-sectional studies performed between 1997 and 2005 on the thyroid. These studies included 376 patients with subclinical hypothyroidism (elevated TSH and normal T4) compared with 7619 patients who were biochemically euthyroid.
The goal of the study reported in this month’s issue was to see if patients who met the serum criteria for subclinical hypothyroidism would manifest symptoms more often than normal individuals. If it were indeed the case that patients with subclinical hypothyroid demonstrated symptoms similar to those observed in patients with true hypothyroid and more often than a euthyroid control population, then a rationale might exist to administer thyroid replacement therapy to individuals with subclinical hypothyroidism.

In the present investigation, Carlé et al2 found that patients with subclinical hypothyroidism had a symptom burden that was the same as that seen in patients with euthyroid. Furthermore, the authors observed that patients with subclinical hypothyroidism had a higher burden of other conditions, for example, pulmonary disease, that were more likely the etiology of the symptoms attributed to subclinical hypothyroidism. The investigators suggest that due to the similar occurrence of symptoms observed in patients with subclinical hypothyroid as compared with subjects who have normal thyroid function, little or no improvement in symptomatology would result from thyroid replacement therapy. A previous prospective study in older adults found no significant benefits of treating subclinical hypothyroidism.2

So, what is the take-home message for readers of The American Journal of Medicine? For us, the message is clear: Subclinical hypothyroidism is, in general, not a clinical entity that requires thyroid replacement therapy, and that relief of symptoms in some of these patients who have received thyroid hormone therapy may well be the result of the placebo effect. Moreover, long-term thyroid treatment of subclinical hypothyroidism might produce inadvertent iatrogenic thyrotoxicosis resulting in increased risk for bone loss and atrial arrhythmias. We agree with Carlé et al2 that treating patients with subclinical hypothyroidism might break the cardinal rule of our profession: First, do no harm.

To read this article in its entirety please visit our website.

-Stuart R. Chipkin, MD, Joseph S. Alpert, MD

This article originally appeared in the May 2021 issue of The American Journal of Medicine.

To read the related paper mentioned in this article, follow this link.

 

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