Treating Thyroid Disease With Triiodothyronine (T3) Drugs

Research suggests it has a rightful place in therapy

T3, natural desiccated thyroid, NDT, levothyroxine, Armour Thyroid
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The American Association of Clinical Endocrinologist (AACE) and American Thyroid Association (ATA) issued guidelines endorsing the use of the drug levothyroxine (marketed under the brand names Synthroid, Levoxyl, and others) as the standard of care for people diagnosed with hypothyroidism (low thyroid function). It is a synthetic hormone known to be safe and effective in replenishing low levels of the thyroid hormone thyroxine, also known as T4.

If you are on levothyroxine but are not feeling well, another drug known as Cytomel (liothyronine) may help. This is the synthetic form of the hormone triiodothyronine, known as T3, which is equally important to healthy metabolic function. Other endocrinologists endorse the use of natural desiccated thyroid (NDT), a form of dried hormones derived from pigs or cows.

Thyroxine vs. Triiodothyronine

Thyroxine (T4) and triiodothyronine (T3) are the two major hormones produced by the thyroid gland. Their role is to regulate metabolism (the conversion of oxygen and calories into energy). Of the two, T3 has four times the hormonal "strength" of T4.

This is because T3 is considered the "active" form of thyroid hormone. It is derived from T4, the "storage" hormone, through a process known as monodeiodination in which T4 loses an atom of iodine to become T3.

While T3 drugs like Cytomel may seem the ideal choice for hormone replacement therapy, T3 is rapidly absorbed in the intestines and can build up quickly, leading to symptoms of hyperthyroidism (overactive thyroid).

By contrast, T4 drugs like levothyroxine are absorbed more gradually and are able to maintain a steady state in the blood, providing the body with all the T4 it needs to synthesize T3.

Another concern is that T3 drugs can affect the T4 blood tests used to monitor the effectiveness of hormone replacement therapy. For these reasons, many doctors consider T3 drugs unnecessary.

Benefits of T3 Treatment

There remains ongoing debate within the endocrinology community about many facets of thyroid treatment, including the appropriate time to start treatment, the use of TSH to direct the initiation of treatment, and the appropriateness of natural desiccated hormones when compared to synthetic hormones.

The benefits of T3 have also been under debate. Despite resistance from many in the treating community, a growing body of research is shedding light on the appropriate use of T3 drugs in people with hypothyroidism. Among them:

  • Research published in the Journal of Clinical Endocrinology reported that a genetic defect, known as a deiodinase polymorphism, can significantly interfere with the conversion of T4 into T3, explaining why some people on levothyroxine fail to respond to treatment.
  • A review of 15 studies by researchers in Spain concluded that the combination of levothyroxine and liothyronine improved mood, quality of life, and overall cognition in people with hypothyroidism compared to levothyroxine alone.
  • Another study overseen by the National Institute of Diabetes and Digestive and Kidney Diseases concluded that supplemental T3 can lower cholesterol levels, reduce body weight, and offer better resolution of hypothyroid symptoms without any additional risks compared to levothyroxine alone.
  • A landmark Danish study showed that levothyroxine plus T3 improved all quality of life measures, including general health, social functioning, mental health, vitality, sensitivity, depression, and anxiety. Moreover, 49 percent of the study participants preferred the combination treatment, compared to only 15 percent who preferred levothyroxine alone.

    The results suggest that T3 drugs are underused and may appropriate for people in whom levothyroxine fails to provide relief. Moreover, when used in combination therapy, concerns about T3-induced hyperthyroidism may be less warranted.

    Cytomel (Liothyronine)

    Cytomel (liothyronine) is used to treat hypothyroidism. It can also be used to treat other thyroid disorders such as goiter or as an adjunctive treatment to thyroid cancer therapy. It was first approved for use by the U.S. Food and Drug Administration in 1956 and is today marketed under different brand names, including Triostat, Levoxyl, and Levothroid.

    Formulation and Dosage

    Cytomel is available as a round, white to off-white tablet in a 5-microgram (mcg), 25-mcg, and 50 -mcg dose. The dosage varies by the condition and the level of thyroid gland dysfunction:

    • For mild hypothyroidism, the recommended starting dosage is 25 mcg once daily. Daily dosage may then be increased by up to 25 mcg every one to two weeks. The usual maintenance dose is 25 to 75 mcg once daily.
    • For severe hypothyroidism, the recommended starting dosage is 5 mcg once daily. This may be increased by 5 to 10 mcg daily every one to two weeks. When 25 mcg daily is reached, the dosage may be increased by 5 to 25 mcg every one to two weeks until a satisfactory response is attained. The usual maintenance dose is 50 to 100 mcg once daily. 
    • For goiter, the recommended starting dosage is 5 mcg once daily. This dosage may then be increased by 5 to 10 mcg daily every one to two weeks. When a 25 mcg dosage is reached, it may be increased every week or two by 12.5 or 25 mcg. The usual maintenance dosage is 75 mcg once daily.
    • For congenital hypothyroidism in newborns, the recommended starting dosage is 5 mcg once daily, increasing by 5-mcg increment every three to four days until the desired response is achieved. Infants a few months old may require only 20 mcg daily for maintenance. At year one, 50 mcg daily may be required. Above three years, a full adult dosage may be necessary.

      Side Effects

      With the exception of triggering hyperthyroid symptoms, side effects from Cytomel are rare. In rare cases, skin reactions, generally mild, have been reported.

      Interactions

      Cytomel is known to interact with certain common medications. Among them:

      • Cytomel and other thyroid hormone drugs can enhance blood clotting. If you are taking anticoagulants (blood thinners) like warfarin, your doctor may need to increase your dose to compensate for this effect.
      • Cytomel can also increase blood insulin levels. The routine monitoring of your blood glucose is recommended if you have diabetes. In some cases, a dose adjustment of your diabetes drugs or insulin may be needed.
      • Estrogen-based contraception may interfere with the bioavailability of Cytomel (the amount of active drug circulating in the blood. Cytomel doses may need to be increased if you are on estrogen-based birth control.
      • Cytomel can potentially increase the side effects of tricyclic antidepressants and even trigger bouts of arrhythmia (abnormal heartbeats). An alteration in the antidepressant dose or a substitute antidepressant may be needed.

      Antacids and the cholesterol-lowering drugs Colestid (colestipol) and Questran (cholestyramine) can interfere with the absorption of Cytomel. To avoid this, always separate the doses of Cytomel and the other drugs by at least four hours.

      Contraindications and Considerations

      Cytomel should not be used in people with untreated adrenal insufficiency (when the adrenal gland do not produce enough of the hormone cortisol) or thyrotoxicosis (excessive thyroid levels by any cause).

      Cytomel is not absorbed in fetal tissue and is therefore considered safe during pregnancy. While liothyronine can be passed through breastmilk, the amount secreted is so small as to be considered harmless.

      Natural Desiccated Thyroid

      Some doctors have found success in treating their thyroid patients with natural desiccated thyroid, also known as NDT. NDT is derived from the dried (desiccated) thyroid gland of pigs or cow and provides T3, T4, and other thyroid hormones found in the human thyroid gland.

      NDT is marketed under various brand names in the United States, including Armour Thyroid, Nature-Throid, and WP Thyroid.

      While natural desiccated thyroid hormone has been used for more than a century to treat thyroid disorder, it has not been approved by the FDA for such treatment.

      Despite this, a growing number of doctors and patients have embraced the NDT as the natural alternative to levothyroxine and liothyronine, including former Secretary of State Hillary Rodham Clinton.

      Formulation and Dosage

      Most NDT brands come in an off-white tablet in 15-, 30-, 60-, 90-, 120-, 180-, 240-, and 300-milligram (mg) doses. Dosages can vary by your condition, lab test results, and response to treatment:

      • For mild hypothyroidism, most doctors start with a 30-mg dosage once daily, increasing by 15 mg per day for six weeks or until the desired response is achieved. The usual maintenance dose is 180 mg once daily.
      • For severe hypothyroidism, it is best to start at a lower dose and increase gradually until the desired response is achieved. The usual maintenance dose is 180 mg once daily.
      • For congenital hypothyroidism, the once-daily dosage varies by age: 15-30 mg for under 6 months, 30-45 mg for 6 to 11 months; 45-60 mg for 1 to 5 years; 60-90 mg for 5 to 12 years; and 90-180 mg for over 12.

      Side Effects

      NDT can potentially cause hyperthyroidism if overused, improperly used, or used without regular thyroid blood testing. Beyond this, side effects are rare, although skin reactions have been known to occur.

      Interactions

      The interactions for NDT are similar to those for Cytomel. Be sure to speak with your doctor about any and all drugs you may be taking, whether they are prescription, over-the-counter, nutritional, homeopathic, naturopathic, traditional, or herbal.

      Contraindications and Considerations

      As with Cytomel, NDT should not be used in people with untreated adrenal insufficiency or thyrotoxicosis and is considered safe during pregnancy and breastfeeding.

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