What is the difference between Levothyroxine (T4) and Liothyronine (T3)?

From the Guidelines

T4 (thyroxine) and T3 (triiodothyronine) are thyroid hormones with distinct differences in function and medical use, with T4 being the primary hormone produced by the thyroid gland and serving mainly as a prohormone that gets converted to the more active T3 in tissues throughout the body. For most people with hypothyroidism, T4 replacement (levothyroxine) is the recommended first-line treatment, typically starting at 25-50 mcg daily for mild cases or 1.6 mcg/kg body weight, with dose adjustments based on TSH levels every 6-8 weeks until stabilized 1. T3 is the more metabolically active hormone, producing effects about four times more potent than T4, but with a shorter half-life (1 day versus 7 days for T4) 1.

Key Differences Between T4 and T3

• T4 is the primary hormone produced by the thyroid gland, while T3 is the more active form of the hormone.
• T4 has a longer half-life (7 days) compared to T3 (1 day).
• T4 is generally used as the first-line treatment for hypothyroidism, while T3 is reserved for special situations.

Medical Use of T4 and T3

• T4 replacement (levothyroxine) is the recommended first-line treatment for most people with hypothyroidism.
• T3 medication (liothyronine) is generally reserved for special situations like myxedema coma, preparation for radioactive iodine treatment, or as combination therapy when T4 alone doesn't resolve symptoms despite normal lab values 1.
• The body's natural conversion process from T4 to T3 allows for stable hormone levels, which is why T4 monotherapy works well for most patients, providing consistent hormone availability while avoiding the peaks and troughs associated with direct T3 supplementation 1.

Important Considerations

• The optimal screening interval for thyroid dysfunction is unknown 1.
• Treatment is generally recommended for patients with a TSH level that is undetectable or less than 0.1 mIU/L, particularly those with overt Graves disease or nodular thyroid disease 1.
• Long-term randomized, blinded, controlled trials of screening for thyroid dysfunction would provide the most direct evidence on any potential benefits of this widespread practice 1.

Recommendation

For most people with hypothyroidism, T4 replacement (levothyroxine) is the recommended first-line treatment, with T3 medication (liothyronine) reserved for special situations. This approach provides consistent hormone availability while avoiding the peaks and troughs associated with direct T3 supplementation, and is supported by the available evidence 1.

From the FDA Drug Label

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues. The mechanisms by which thyroid hormones exert their physiologic action are not well understood. These hormones enhance oxygen consumption by most tissues of the body, increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins T4 contains four iodine atoms and is formed by the coupling of two molecules of diiodotyrosine (DIT) T3 contains three atoms of iodine and is formed by the coupling of one molecule of DIT with one molecule of monoiodotyrosine (MIT). The higher affinity of levothyroxine (T4) for both thyroid-binding globulin and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone

The main difference between Levothyroxine (T4) and Liothyronine (T3) is:

• Chemical structure: T4 contains four iodine atoms, while T3 contains three iodine atoms.
• Biological activity: T3 is the more active form of the hormone, with the majority (approximately 80%) of T3 being derived from T4 by deiodination in peripheral tissues.
• Half-life: T4 has a longer half-life compared to T3, with a half-life of 6-7 days for T4 and approximately 2-1/2 days for T3 2, 3.
• Protein binding: T4 has a higher affinity for thyroid-binding globulin and thyroid-binding prealbumin, resulting in higher serum levels and a longer half-life compared to T3 2, 3.

From the Research

Difference between Levothyroxine (T4) and Liothyronine (T3)

• Levothyroxine (T4) is a synthetic form of the thyroid hormone thyroxine, which is converted to triiodothyronine (T3) in the body 4, 5, 6.
• Liothyronine (T3) is a synthetic form of the thyroid hormone triiodothyronine, which is the active form of thyroid hormone 5, 6, 7.

Key Differences

• T4 is converted to T3 in the body, whereas T3 is the active form of thyroid hormone that directly affects the body's metabolism 6, 7.
• T4 has a longer half-life than T3, which means it stays in the body longer 5, 8.
• Some patients may not respond well to T4 alone and may require T3 supplementation to alleviate symptoms of hypothyroidism 5, 6, 7.

Clinical Use

• T4 is the standard treatment for hypothyroidism, but some patients may prefer combination therapy with T3 5, 8.
• The use of T3 supplementation is controversial, and more research is needed to determine its effectiveness and safety 5, 6, 7.
• The T3/T4 ratio may be used as a marker of clinical response to levothyroxine replacement in patients with hypothyroidism 7.