T4

The body has a feedback system that turns thyroid hormone production on and off. When the level of T4 in the bloodstream decreases, the hypothalamus (an organ in the brain) releases thyrotropin releasing hormone, which stimulates the pituitary gland (an organ below the hypothalamus) to release thyroid-stimulating hormone (TSH), which in turn stimulates the thyroid gland to make and/or release more T4. As blood concentrations of T4 increase, TSH release is inhibited.

T4 makes up nearly 90% of thyroid hormones, while T3 makes up less than 10%. Inside the thyroid gland, T4 is bound to a protein called thyroglobulin. When the body requires thyroid hormone, the thyroid gland releases stored T4 into circulation. In the blood, T4 is either free (not bound) or protein-bound (primarily bound to thyroxine-binding globulin). The concentration of free T4 is only about 0.1% of that of total T4. T4 is converted into T3 in the liver or other tissues. T3, like T4, is also highly protein-bound, but it is the free forms of T3 and T4 that are biologically active. Free T3 is also 4 to 5 times more active than free T4 in circulation.

If the thyroid gland does not produce sufficient T4, due to thyroid dysfunction or to insufficient TSH, then the affected patient experiences symptoms of hypothyroidism such as weight gain, dry skin, cold intolerance, irregular menstruation, and fatigue. If the thyroid gland produces too much T4, the rate of the patient’s body functions will increase and cause symptoms associated with hyperthyroidism such as increased heart rate, anxiety, weight loss, difficulty sleeping, tremors in the hands, and puffiness around dry, irritated eyes.

The most common causes of thyroid dysfunction are autoimmune-related. Graves’ disease causes hyperthyroidism and Hashimoto’s thyroiditis causes hypothyroidism. Both hyper- and hypothyroidism can also be caused by thyroiditis (thyroid inflammation), thyroid cancer, and excessive or deficient production of TSH. The effect of these conditions on thyroid hormone production can be detected and monitored by measuring the total T4 (includes bound and free portion) or the free T4 (unbound form).