The Thyroid Conundrum

What to do when symptoms don't match up.
May 7, 2021
Arana Crisler, Fort Wayne Endocrinology
The Thyroid Conundrum

Thyroid hormone is perhaps the most widely misunderstood of all hormones. When a patient presents with a variety of chronic or progressive hypothyroid-like symptoms, yet the thyroid stimulating hormone (TSH) level is normal on repeat testing, what do you do? 

Consider not only that the thyroid gland produces two major thyroid hormones: levothyroxine (T4) and liothyronine (T3), but involves complex pathways including several iso-forms of deiodinase called type I deiodinase (D1) and type II deiodinase (D2). D2 is predominantly found in the pituitary gland and D1 is found in the peripheral tissues such as fat and muscle cells. The deiodinase enzyme is extremely susceptible to inactivation by endocrine disruptors, with D2 being relatively more resistant to disruptors. Hence D2 in the pituitary gland may be functioning optimally while D1 is being disrupted. 

What follows is a dichotomy of physiological effects with the possibility of the pituitary gland signaling adequate thyroid status by virtue of a normal TSH level. Meanwhile, the rest of the body, governed by D1, might be experiencing hypothyroidism. This explains how some patients experience clinical hypothyroid or hypometabolic states despite a TSH level within normal range. It is important to note that in such cases T4 replacement alone, such as levothyroxine, will not provide significant benefits since the main problem lies in the peripheral conversion of T4 to T3 by the enzyme D1. 

Various medical society guidelines for the treatment of hypothyroidism fail to address this issue. These guidelines narrowly apply to a subset of primary hypothyroidism, leaving out the many patients who suffer from hypometabolism despite normal TSH levels. Leaving out an acknowledgement of the greater thyroid system and trying to apply these guidelines to such patients is inadequate. 

Guidelines are manufactured by a small group of individuals and typically issue a disclaimer that they are not to be considered standard of care or all encompassing, and that care must be evaluated on a case by case basis. Holding one’s feet to the fire based on guidelines would be effectively commoditizing the art of medical practice and would be counterproductive to the health of the patient. These guidelines are meant to be a starting point in managing disease states. 

Furthermore, studies that discredit the use of T3 replacement have used a very small dose of T3 replacement, such as 5mcg, with a conclusion that it made no difference. Hence, had they used a therapeutic dose of T3, consider how the conclusions on T3 replacement’s clinical effectiveness might be quite different. Sir William Osler once remarked, listen to your patient; she/he is telling you the diagnosis. Perhaps it is time we heed Dr. Osler’s advice and apply it in our day to day practice.


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