Controversies In The Diagnosis and Treatment of Hypothyroidism

Diagnosis of hypothyroidism: Why TSH testing may not be an accurate marker of tissue thyroid levels

Hypothyroidism is a common disorder characterized by an inadequate cellular thyroid effect to meet the needs of the tissues. Typical symptoms of hypothyroidism include the following: fatigue, weight gain, depression, cold extremities, muscle aches, headaches, decreased libido, weakness, cold intolerance, water retention, premenstrual syndrome (PMS), and dry skin. Low thyroid causes or contributes to the symptoms of many conditions, but the deficiency is often missed by standard thyroid testing. This is frequently the case with such conditions as depression, hypercholesterolemia (high cholesterol), menstrual irregularities, infertility, PMS, chronic fatigue syndrome (CFS), fibromyalgia, fibrocystic breasts, polycystic ovary syndrome (PCOS), hyperhomocysteinuria (high homocystine), atherosclerosis, hypertension, obesity, diabetes, and insulin resistance.

The TSH test is generally considered the most sensitive marker of peripheral tissue levels of thyroid. We believe this view, however, is incorrect. Most endocrinologists and other physicians erroneously assume that, except for unique situations, a normal TSH is a clear indication that the person’s tissue thyroid levels are adequate (symptoms are not due to low thyroid). But a more thorough understanding of the physiology of hypothalamic-pituitary-thyroid axis and tissue regulation of thyroid hormones exposes as clearly erroneous the widely held belief that the TSH is an accurate marker of the body’s overall thyroid status.

The TSH is inversely correlated with pituitary T3 levels; but with physiologic stress (1-32), depression (33-38), insulin resistance and diabetes (28,39,116,117), aging (30,40-49), calorie deprivation (dieting)(27, 50-57), inflammation (5-8,22,108,109-111), PMS (58,59), chronic fatigue syndrome and fibromyalgia (60,61), obesity (112,113,114), and numerous other conditions (1-32), increasing pituitary T3 levels are often associated with diminished cellular and tissue T3 levels and increased reverse T3 levels in the rest of the body (1-62) (see pituitary diagram). The pituitary is both anatomically and physiologically unique, reacting differently to inflammation, chronic calorie reduction (dieting) and physiologic stress than every other tissue in the body (1-20,50-52,62,63). During physiologic stress or dieting there is a reduced conversion of T4 to T3 and an increase in the formation of the anti-thyroid reverse T3 in tissues throughout the body except for the pituitary, where local mechanisms to increase pituitary T3 levels (1-63).


Physiologic stress, depression, emotional stress and chronic dieting also result in the abnormal stimulation other mechanisms that reduce cellular thyroid activity but is not detected by standard blood tests. This abnormal metabolic pathway converts T4 into a substance called tetraiodothyroacetic acid (Tetrac) and T3 into a substance called triiodothyroacetic acid (Triac) (128-132). The levels of Tetrac and Triac increase two to twelve-fold with dieting or physiologic stress (129-132). Both these substances are selectively taken up by the pituitary and suppress TSH production but have no effect in the rest of the body (128,129,134-137). Everts et al found that Triac is twice as potent as T3 at suppressing TSH secretion and 20 times more potent than T4 at suppressing TSH secretion (137). Thus, with physiologic or emotional stress, chronic dieting, depression and inflammation, the pituitary T3 levels do not correlate with T3 levels in the rest of the body–the TSH does not rise despite significant cellular hypothyroidism. This is another reason that the TSH is not a reliable or sensitive marker of an individual’s true thyroid status if such common conditions are present and is another reason that a TSH cannot be relied upon as an accurate marker for tissue thyroid status.

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