Chronic physiologic stress results in decreased D1 activity (11,12,13-17,234) and an increase in D3 activity (1,195,196), decreasing thyroid activity by converting T4 into reverse T3 instead of T3 (1,195,196,216,234). Conversely, D2 is stimulated, which results in increased T4 to T3 conversion in the pituitary and reduced production of TSH (11,16,18-22,234). The increased cortisol levels seen with stress also contribute to physiologic disconnect between the TSH and peripheral tissue T3 levels (16,18-20). This stress induced reduced tissue T3 level and increased reverse T3 results in tissue hypothyroidism and potential weight gain, fatigue, and depression (12,13,194,217-219). This vicious cycle of weight gain, fatigue, and depression that is associated with stress can be prevented with supplementation with timed-released T3 (25,26,52,121-124,199,201-215,220,221) but not T4 (52,197-199,201,222,223).
The reduced immunity from chronic stress has been thought to be due to excess cortisol production; but the associated reduction in tissue thyroid levels are shown to play a larger role in the decreased immunity seen with stress, and thyroid supplementation is shown to reverse the stress induced reduction in immunity (217).
As with stress, treatment with prednisone or other glucocorticoid will suppress D1 and stimulate D3, reducing T4 to T3 conversion and increasing T4 to reverse T3, causing a relative tissue hypothyroidism that is not detected by TSH testing (12,18-21,194,218,224). This low cellular thyroid level certainly contributes to the weight gain and other associated side-effects with such treatment. Thus, in stressed patients or those treated with corticosteroids, there are reduced tissue T3 levels that are not reflected by the TSH level, making the TSH an inappropriate marker for tissue levels of T3.