For hypothyroidism (underactive thyroid), do you need to give triiodothyronine (T3) in addition to levothyroxine (T4), and what type of T3 should be checked?

From the Guidelines

For most patients with hypothyroidism, levothyroxine (T4) alone is sufficient treatment, and additional triiodothyronine (T3) therapy is not routinely needed. The standard approach is to start with levothyroxine monotherapy, typically at a dose of 1.6 mcg/kg/day, adjusted based on thyroid-stimulating hormone (TSH) levels 1. When monitoring thyroid function, the primary lab value to check is TSH, with a target range of 0.4-4.0 mIU/L for most adults. Free T4 levels may also be checked, especially during dose adjustments. Routine testing of T3 levels (either total T3 or free T3) is not recommended for patients on standard levothyroxine therapy. However, in specific situations where patients continue to experience symptoms despite normal TSH levels on levothyroxine alone, free T3 levels may be checked to assess peripheral conversion of T4 to T3. Combination T4/T3 therapy remains controversial and should only be considered in select patients who have persistent symptoms despite optimal T4 therapy and normal TSH levels 1. This approach works because T4 serves as a prohormone that is converted to the more active T3 in peripheral tissues, providing stable hormone levels throughout the day for most patients. Some key points to consider when treating hypothyroidism include:

• The principal treatment for hypothyroidism is oral T4 monotherapy (levothyroxine sodium) 1.
• Hyperthyroidism is treated with antithyroid medications (such as methimazole) or nonreversible thyroid ablation therapy (for example, radioactive iodine or surgery) 1.
• The optimal screening interval for thyroid dysfunction is unknown 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.
• The effects of treatment of thyroid dysfunction on important clinical outcomes may be independent of any known intermediate outcomes 1.

From the FDA Drug Label

The rapid onset and dissipation of action of liothyronine sodium (T3), as compared with levothyroxine sodium (T4), has led some clinicians to prefer its use in patients who might be more susceptible to the untoward effects of thyroid medication Liothyronine Sodium Tablets, USP may be used in preference to levothyroxine (T4) during radioisotope scanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of T4 to T3 is suspected.

For hypothyroidism, T3 (liothyronine sodium) may be given in addition to T4 (levothyroxine) in certain situations, such as:

• When impairment of peripheral conversion of T4 to T3 is suspected
• During radioisotope scanning procedures
• In patients who might be more susceptible to the untoward effects of thyroid medication The type of T3 that should be checked is serum T3 levels, as the drug label mentions that the wide swings in serum T3 levels follow the administration of liothyronine sodium (T3) 2.

From the Research

Hypothyroidism Treatment with T3 and T4

• For patients with hypothyroidism, levothyroxine (T4) is the standard treatment, but some patients may not fully respond to T4 therapy alone 3.
• In such cases, adding triiodothyronine (T3) to the treatment regimen may be considered, with a starting dose of 2.5-7.5 mcg of liothyronine (LT3) once or twice a day 3.
• The type of T3 to be checked is not explicitly specified, but studies suggest that measuring T3 levels may not be informative in assessing T4 over-replacement in hypothyroid patients 4.

T3 Testing in Hypothyroidism

• T3 testing is not recommended for assessing levothyroxine (T4) over-replacement in hypothyroid patients, as T3 levels can be normal even in over-replaced patients 4.
• However, measuring the T3/T4 ratio may be useful in assessing clinical response to levothyroxine replacement in patients with hypothyroidism, with lower ratios associated with persistent symptoms 5.
• Studies have shown that T3 levels can be subnormal in patients with severe primary hypothyroidism, even when T4 levels are normal, and that T3 concentrations can be used to assess the adequacy of T4 replacement therapy 6.

Combination Therapy with T4 and T3

• Combination therapy with T4 and T3, such as liothyronine (LT3) or desiccated thyroid extract (DTE), may be considered for patients who do not respond to T4 therapy alone 3, 7.
• However, the use of compounded T4/T3 therapy is not recommended, as it can lead to iatrogenic hypothyroidism and other adverse effects 7.
• The American Thyroid Association recommends against the routine use of compounded thyroid hormone therapy, and instead suggests using FDA-approved T4 and T3 preparations 7.