The review demonstrates that TSH serum levels are poor indicators of T3 tissue levels and that despite normal serum thyroid levels patients may have low tissue T3 and be functionally hypothyroid. It reports the effects of stress, depression, pain, dieting, insulin resistance, leptin, exercise, iron deficiency, inflammation, environmental toxins, testosterone and growth hormone on T3 tissue levels under individual headings.
There have been recent advances in understanding of the local control of thyroid activity and metabolism, including deiodinase activity and thyroid hormone membrane transport. The goal of this review is to increase the understanding of the clinical relevance of cellular deiodinase activity. The physiologic significance of types 1, 2 and 3 deiodinase (D1, D2 and D3, respectively) on the intracellular production of T3 are discussed along with the importance and significance of the production of reverse T3. The difference in the pituitary and peripheral activity of these deidoidinases under a wide range of common physiologic conditions results in different intracellular T3 levels in the pituitary and peripheral tissues, resulting in the inability to detect low tissue levels of thyroid hormone in peripheral tissues with TSH testing. This review demonstrates that extreme caution should be used in relying on TSH or serum thyroid levels to rule out hypothyroidism in the presence of a wide range of conditions, including physiologic and emotional stress, depression, dieting, obesity, leptin insulin resistance, diabetes, chronic fatigue syndrome, fibromyalgia, inflammation, autoimmune disease, or systemic illness, as TSH levels will often be normal despite the presence of significant hypothyroidism. The review discusses the significant clinical benefits of thyroid replacement in such conditions despite having normal TSH levels and the superiority of T3 replacement instead of standard T4 therapy.
With an improved understanding of thyroid physiology that includes the local control of intracellular activation and deactivation of thyroid hormones by deiodinases, it becomes clear that standard thyroid tests often do not reflect the thyroid status in the tissues of the body, other than the pituitary. This is especially true with physiologic and emotional stress, depression, dieting, obesity, leptin insulin resistance, diabetes, chronic fatigue syndrome and fibromyalgia, inflammation, autoimmune disease, or systemic illness. Consequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator of normal or low tissue levels of T3 in the presence of any such conditions, making the TSH a poor marker for the body’s overall thyroid level.
In order to be appropriately and thoroughly evaluated for thyroid dysfunction and obtain optimal treatment, it is important that patients find a thyroidologist who understands the limitations of standard thyroid testing and can clinically evaluate patients by taking an extensive inventory of potential signs and symptoms that may be due to low tissue thyroid levels despite normal standard thyroid tests.