Treatment with Thyroid Hormones with “Normal” Blood Tests
The presence of thyroid dysfunction in nonthyroidal illness (NTIS Nonthyroidal Illness Syndrome, previously known as the Euthyroid sick syndrome) is well-described in the medical literature and is particularly receiving attention in recent years in the critical care literature. This is believed to represent both hypothalamic-pituitary axis dysfunction (thus a “normal” TSH in the presence of clinical hypothyroidism) as well as altered peripheral metabolism of tetraiodothyronine (production of rT3 instead of T3 in tissues) and perhaps changes in hormone binding. In addition, there are environmental causes of thyroid hormone resistance at the receptor level in our modern world . As one example, PCB’s actually cause mental retardation in the developing fetus by interfering with thyroid hormone binding to its receptor or gene activation normally induced by thyroid hormone.
The result of all of these factors is that often in persons with other illnesses (autoimmune disease, chronic fatigue syndrome, chronic infection), or even after significant weight loss or other stressors, there will be a clinical syndrome consistent with hypothyroidism (cold intolerance, constipation, dry skin, depression, etc.) without clear laboratory evidence of hypothyroidism. In this situation, I often have people measure basal body temperatures as a nonspecific indicator, and if these run low in conjunction with suggestive symptoms, I will give a trial of therapy of thyroid hormone replacement. If there is no improvement in symptoms, we consider that a failed trial and stop the hormones. If symptoms improve on the thyroid hormone, we then monitor for toxicity and decrease the dose if the TSH is suppressed. I have found this to make a significant difference in the quality of life for many of my patients, and feel it is safe as long as laboratory monitoring is performed. If patients are feeling well, many of them later can taper off the thyroid replacement, after the underlying illness that triggered the syndrome has been addressed.
Treatment of Hypothyroidism with Armour or Dessicated Thyroid rather than Levothyroxine
Another controversial point is the use of armour thyroid rather than levothyroxine for thyroid hormone replacement. The medical literature is split as to whether there is any benefit to providing a mixture of T3 with T4 as opposed to pure T4 replacement therapy. A 1999 study published in the New England Journal of Medicine found improved control of symptoms of hypothyroidism, particularly psychiatric symptoms, with combination therapy. Other studies have shown no difference, but many of those studies have excluded participants with a history of depression.
There are unrelated studies in the psychiatric literature reporting the use of liothyronine(cytomel, pure T3) for the augmentation of antidepressant therapy, even in persons who are clinically euthyroid, often with dramatic results (up to doubling of the response rate compared to the placebo group). There is also a body of literature addressing genetic polymorphisms in the D1, D2, and D3 iodothyronine deiodinases and their impact on thyroid function and hormone levels, confirming a plausible basis for genetic differences in the handling of thyroid hormones.
I have found, and the above studies support this, that many patients feel fine on levothyroxine , in which case I am happy to continue this as their primary thyroid replacement. There is a significant subset of patients, however, often those with chronic dysthymia or depression, who notice an improvement in symptom control when placed on armour thyroid instead.
One issue with armour thyroid is that the ratio of T3:T4 is 1:5, whereas a more normal ratio in humans is often 1:10. Laboratory monitoring of patients on armour will thus often reveal a low free T4 with a normal TSH, and if symptoms are controlled I will leave this as is. Some patients feel symptoms of excessive thyroid replacement (palpitations, nervousness, shaky hands, etc.) related to the high T3, however, and in those patients I will generally switch to levothyroxine or, in a few patients (and myself!), use a combination of the two to more closely approximate normal thyroid physiology.
Connie Basch, M.D March 2008
