Wilson's Syndrome- Reverse T3 Dominance

The thyroid is a small, butterfly-shaped gland located just below the Adam's apple. This gland plays a very important role in controlling your body's metabolism, that is, the rate at which your body uses energy. It does this by producing thyroid hormones (primarily thyroxine, or T4, and triiodothyronine, or T3). These thyroid hormones tell the cells in your body how fast to use energy and create proteins. The thyroid gland also makes calcitonin, a hormone that helps to regulate calcium levels in the blood by inhibiting the breakdown (reabsorption) of bone and increasing calcium excretion from the kidneys.

In a healthy patient a normal thyroid gland secretes all of the circulating T4 (about 90 to 100mcg daily) and about 20% of the circulating T3. The T4 made by the thyroid gland circulates throughout the body and is converted into roughly equal amounts of T3 and reverse T3. Most of the biological activity of thyroid hormones is due to T3. It has a higher affinity for thyroid receptors and is approximately 4 times more potent than T4. Because 80% of serum T3 is derived from T4 in tissues such as the liver and kidney, T4 is considered a pro-hormone. No receptors have ever been identified for T4.

Reverse T3 (rT3) is virtually inactive having only 1% the activity of T3 and being a T3 antagonist binds to T3 receptors blocking the action of T3. Normal metabolism of T4 requires the production of the appropriate ratio, or balance, of T3 to rT3. If the proportion of rT3 dominates then it will antagonize T3 thus producing hypothyroid symptoms despite sufficient circulating levels of T4 and T3. Reverse T3 has the same molecular structure as T3 however its three dimensional arrangement (stereochemistry) of atoms is a mirror image of T3 and thus fits into the receptor upside down without causing a thyroid response and thus preventing or antagonizing the active T3 from binding to the receptor acting as a metabolic break.

Reverse T3 dominance, also known as Wilson's Syndrome, is a condition that exhibits most hypothyroid symptoms although circulating levels of T3 and T4 are within normal test limits. The metabolism of T4 into rT3 is in excess when compared to T3 therefore it is a T4 metabolism malfunction rather than a straight forward thyroid deficiency. Periods of prolonged stress, may cause an increase in cortisol levels as the adrenal glands respond to the stress. The high cortisol levels inhibit the conversion of T4 into T3 thus reducing active T3 levels. The conversion of T4 is then shunted towards the production of the inactive reverse T3. This reverse T3 dominance may persist even after the stress passes and cortisol levels have returned to normal as the reverse T3 itself may also inhibit the conversion of T4 to T3 thus perpetuating the production of the inactive reverse T3 isomer. Also conversion of T4 into T3 is decreased in the following cases that need to be rules out, such as hypoglycemia (low blood sugar-possibly due to low carb diets), adrenal exhaustion, nutritional deficiencies (such as Vit B6, B12, Zinc, Vit E and iodine) and/or low sex hormone (such as testosterone).

Therefore, besides testing for TSH, Free T4, Free T3, rT3, is also tested, and a ratio of T3/rT3 is obtained. If reverse T3 dominance is present appropriate therapy is needed to safely treat the patient, and relieve all symptoms that brought them into the physician's office in the first place.