Thyroid hormone production is regulated by a feedback system involving the hypothalamus and pituitary gland in the brain and also the thyroid gland located in the neck.

The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the pituitary gland to secrete thyroid-stimulating hormone (TSH).

Changes in TSH often occur before the actual level of thyroid hormones in the body becomes too high or too low. A high TSH level happens when the thyroid gland is not making enough thyroid hormone (primary hypothyroidism), as the body regulates and tries to stimulate more thyroid hormone production. When the TSH level is low it indicates that the thyroid is producing too much thyroid hormone.  Occasionally, a low TSH may result from an abnormality in the pituitary gland, which prevents it from making enough TSH to stimulate the thyroid (secondary hypothyroidism).

TSH then stimulates the thyroid gland to produce and secrete the thyroid hormones T4 (thyroxine). T4 exists both protein-bound and free T4 hormone.  T4 is converted to T3 (triiodothyronine) by the removal of an iodine atom.

T3 tests are most useful to diagnosis hyperthyroidism (which would have an elevated T3 level). T3 testing rarely is helpful in the hypothyroid patient, since it is the last test to become abnormal. 

Reverse T3 is a biologically inactive protein that is structurally very similar to T3, but the iodine atoms are placed in different locations, which makes it inactive. Some reverse T3 is produced normally in the body, but is then rapidly degraded. In general, measurement of reverse T3 does not help determine whether hypothyroidism exists or not, and is not clinically useful.