The production of T4 and T3 in the thyroid gland is regulated by the hypothalamus and pituitary gland. To ensure stable levels of thyroid hormones, the hypothalamus monitors circulating thyroid hormone levels and responds to low levels by releasing thyrotropin-releasing hormone (TRH). This TRH then stimulates the pituitary to release thyroid stimulating hormone (TSH).9,10 When thyroid hormone levels increase, production of TSH decreases, which in turn slows the release of new hormone from the thyroid gland.
Cold temperatures can also increase TRH levels. This is thought to be an intrinsic mechanism that helps keep us warm in cold weather.11
Elevated levels of cortisol, as seen during stress and in conditions such as Cushing’s syndrome, lowers TRH, TSH and thyroid hormone levels as well.12,13
The thyroid gland needs iodine and the amino acid L-tyrosine to make T4 and T3. A diet deficient in iodine can limit how much T4 the thyroid gland can produce and lead to hypothyroidism.14
T3 is the biologically active form of thyroid hormone. The majority of T3 is produced in the peripheral tissues by conversion of T4 to T3 by a selenium-dependent enzyme. Various factors including nutrient deficiencies, drugs, and chemical toxicity may interfere with conversion of T4 to T3.15
Another related enzyme converts T4 to an inactive form of T3 called reverse T3 (rT3). Reverse T3 does not have significant thyroid hormone activity.16
Ninety-nine percent of circulating thyroid hormones are bound to carrier proteins, rendering them metabolically inactive. The remaining “free” thyroid hormone, the majority of which is T3, binds to and activates thyroid hormone receptors, exerting biological activity.17 Very small changes in the amount of carrier proteins will affect the percentage of unbound hormones. Oral contraceptives, pregnancy, and conventional female hormone replacement therapy may increase thyroid carrier protein levels and, thereby, lower the amount of free thyroid hormone available.18