Thyroid Hormone: T4-T3 Combination Therapy

Thyroid Hormone (TH) is produced by the thyroid gland in response to the release of thyroid stimulating hormone (TSH) from the pituitary gland. TH helps the body convert food into energy and heat, regulates body temperature, and impacts many other hormonal systems in the body.

TH exists in two major forms: thyroxine (T4), an inactive form that is produced exclusively by the thyroid gland; and triiodothyronine (T3), the active form of thyroid hormone. About 20 percent of T3 is produced by the thyroid gland, with the remainder produced through conversion of T4 in various tissues of the body when more T3 is needed. Some people may transform T4 into a non-usable form called Reverse T3.

TH helps control heart rate and blood pressure and therefore TH imbalance has a profound effect on cardiovascular fitness. When TH levels drop, the liver no longer functions properly and produces excess cholesterol, fatty acids, and triglycerides, which increase the risk of heart disease. Hypothyroidism (low levels of thyroid hormone) is the second leading cause of high cholesterol, after diet. High cholesterol may also increase the risk of Alzheimer's disease, and severe hypothyroidism can cause symptoms similar to those of Alzheimer's disease.

The drug most commonly used to treat hypothyroidism is a type of T4 known as levothyroxine (brand name Synthroid®). A study published in December 2009 in the European Journal of Endocrinology evaluated quality of life, depression and anxiety rating scales and patients’ preferences and concluded that a combination of T4/T3 is superior to treatment with only T4 (levothyroxine) for hypothyroidism.

Some previous studies have shown the superiority of the combination therapy while others have found no difference. This inconsistency has led some experts to conclude that there is no benefit of using T3 for thyroid hormone therapy. Doctors often point to the risk of side effects with T3 therapy as a reason not to use T3, but the above mentioned study, which replaced part of the T4 dose with 20 mcg of T3, showed that there was no difference with regard to side effects. According to the authors, during the T4/T3 combination therapy, five people experienced side effects including palpitations, excessive sweating, and psychological instability. During the T4-only therapy, nine people reported the same side effects.

The theory behind the use of synthetic T4 alone (levothyroxine) is that the thyroid makes T4 which the body converts to T3. However, in some people, the conversion to T3 may be inadequate, and this is why T3 may therapy may also be needed in some patients. Synthetic T3 (liothyronine) is commercially available only as an immediate-acting preparation, which may cause undesirable side effects including heart palpitations in the recommended dose of 50-100 mcg. That is why some practitioners choose to use lower doses of T3 or provide T3 as a sustained release preparation, both of which are available from our compounding pharmacy.

Armour Thyroid® (Desiccated Natural Thyroid, Thyroid USP) is a blend of T4-T3 that is also used to treat hypothyroidism. Many patients prefer Desiccated Natural Thyroid, reporting that they simply do not feel as well when they take levothyroxine alone or with liothyronine. Recently, there has been a nationwide shortage of Armour Thyroid® in some strengths, and the manufacturer has not indicated any date when all strengths of the product will be back on the market.

Currently, Desiccated Natural Thyroid - Thyroid USP (porcine) - is available in all strengths only through compounding pharmacies. The specifications for Thyroid USP (porcine) powder require that each grain contains levothyroxine (T4) 34.2-41.8 mcg and liothyronine (T3) 8.1-9.9 mcg. This produces a T4:T3 ratio of 4.22:1 to meet the stringent standards for a U.S. Pharmacopeia monograph, with a permissible variance of ± 10%.

By prescription, we can compound Thyroid USP in the doses that your patients need, and can omit problem-causing fillers and excipients that are found in the commercial product but may not be tolerated by all patients. We welcome your questions and the opportunity to work with patients and their health care providers to solve medication problems.

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