Low T3 Level: An Indication for Treatment?

I am an adult psychiatric nurse practitioner, and a significant part of my practice has been the treatment of subclinical hypothyroidism. Whenever a patient has depression and low energy, I measure free T₄, free T₃, and thyroid-stimulating hormone (TSH) levels. In most of the subclinical hypothyroidism I have detected, the TSH level is normal. In many cases, the only level that is low is the free T₃. When liothyronine is prescribed for these patients, their symptoms of depression and tiredness decrease and their need for antidepressants has, in a few cases, been eliminated.

My goal is to get patients' levels to the middle of the normal ranges for free T₄ (1.1 ng/dL) and free T₃ (3.3 pmol/L). I have found that a free T₃ level of less than 2.7 pmol/L is significant and that supplementation makes a difference. A free T₄ level of less than 1.0 ng/dL with a corresponding free T₃ level of less than 2.8 pmol/L is significant enough to treat, and I have not been disappointed in the results of treatment.

My experience is all anecdotal, and these tests do cost more than a standard approach. However, I believe that the end result is cost-effective when one considers the number of failed trials with medications, continuation of depression, and patient nonproductivity seen with more standard therapy. I would be interested to hear what an expert thinks of this approach.

-John V. Billings, MS, ARNP
  Spokane, Wash

First, the definition of subclinical hypothyroidism is an elevated serum TSH level with normal free T₄ and T₃ levels, so the approach you describe is not a treatment for subclinical hypothyroidism. Second, free T₃ assays are notoriously variable. Third, non-thyroidal illness, including depression, may suppress serum T₃ and free T₃ levels; only in severe cases, in which TSH levels are also suppressed, could one argue that these patients have acquired central hypothyroidism. However, even in cases in which T₃, free T₃, and TSH levels are all suppressed, most experts do not recommend treatment. Finally, liothyronine (T₃) treatment should increase T₃ levels but reduce T₄ levels, because of negative feedback on pituitary TSH; this effect should make it difficult to maintain a free T₄ level of 1.1 ng/dL unless only tiny doses of liothyronine are administered.

A large body of literature suggests that liothyronine may be of benefit in depression; however, in most studies, liothyronine was used pharmacologically to cause mild hyperthyroidism, with its associated risks to the heart (atrial arrhythmias) and bone (osteoporosis). Experts have long argued that patients feel better when given a little more thyroid hormone, based on anecdotal experience similar to yours, as well as non-blind trials. Hypothyroid symptoms were recently the subject of double-blind, randomized controlled studies. In one study, patients could not distinguish their usual dose of thyroxine from doses that were 25 to 50 µg/d higher. In other studies, up to 40% of patients given placebo had improved symptom scores. Because hypothyroid symptoms are so nonspecific and because overzealous treatment with thyroid hormone can be dangerous, I do not think that empiric treatment of low free T₃ levels with liothyronine is appropriate in the absence of benefit demonstrated in a blind trial.

- Douglas S. Ross, MD
  Associate Professor of Medicine
  Harvard Medical School
  Cambridge, Mass