What is liothyronine and what is its typical dosing for hypothyroidism?

Liothyronine: Synthetic T3 for Hypothyroidism

Liothyronine is synthetic triiodothyronine (T3), the active thyroid hormone, used primarily as an alternative or adjunct to levothyroxine in hypothyroidism, with typical starting doses of 5-25 mcg daily depending on indication. 1

What is Liothyronine?

Liothyronine is the synthetic form of T3, the more metabolically active thyroid hormone compared to T4 (levothyroxine). 1 Unlike levothyroxine, which requires peripheral conversion to T3, liothyronine provides direct T3 replacement. 2 The drug has a rapid onset of action but also rapid dissipation, with metabolic effects persisting only a few days after discontinuation. 1

Standard Dosing by Indication

Mild Hypothyroidism

• Starting dose: 25 mcg daily 1
• Increase by up to 25 mcg every 1-2 weeks as needed 1
• Usual maintenance: 25-75 mcg daily 1

Myxedema (Severe Hypothyroidism)

• Starting dose: 5 mcg daily 1
• Increase by 5-10 mcg daily every 1-2 weeks 1
• Once 25 mcg daily is reached, may increase by 5-25 mcg every 1-2 weeks 1
• Usual maintenance: 50-100 mcg daily 1

Combination Therapy with Levothyroxine

• Reduce levothyroxine dose by 25 mcg/day and add 2.5-7.5 mcg liothyronine once or twice daily 2
• This approach is recommended for patients who remain symptomatic on levothyroxine monotherapy despite normalized TSH 2
• The typical LT4/LT3 ratio in combination therapy approximates 4:1 2

Special Populations

Elderly or Pediatric Patients:

• Start with 5 mcg daily 1
• Increase only by 5 mcg increments at recommended intervals 1

Congenital Hypothyroidism:

• Starting dose: 5 mcg daily with 5 mcg increments every 3-4 days 1
• Infants may require only 20 mcg daily for maintenance 1
• At 1 year: 50 mcg daily may be required 1
• Above 3 years: full adult dosage may be necessary 1

Key Clinical Considerations

Advantages Over Levothyroxine

• Rapid onset makes it preferable during radioisotope scanning procedures, allowing more abrupt and shorter-duration hypothyroidism induction 1
• May be preferred when impairment of peripheral T4 to T3 conversion is suspected 1
• Some clinicians prefer it for patients more susceptible to untoward effects of thyroid medication due to its rapid cutoff 1

Important Limitations and Risks

• Wide swings in serum T3 levels follow administration, which can be problematic 1
• More pronounced cardiovascular side effects compared to levothyroxine 1
• These disadvantages tend to counterbalance the stated advantages of rapid action 1

Evidence for Combination Therapy

• Trials following almost 1000 patients for nearly 1 year indicate that LT4+LT3 therapy can restore euthyroidism while maintaining normal TSH, similar to LT4 alone 2
• An observational study of 400 patients with mean follow-up of ~9 years showed no increased mortality or morbidity risk from cardiovascular disease, atrial fibrillation, or fractures after age adjustment compared to LT4-only patients 2
• However, numerous randomized trials have failed to show consistent benefit of combination therapy over levothyroxine monotherapy 3, 4

When to Consider Liothyronine

The decision should be reserved for:

• Patients with confirmed overt hypothyroidism who remain symptomatic after adequate levothyroxine treatment (TSH 0.3-2.0 mU/L for 3-6 months) 3
• After excluding other comorbidities that could explain persistent symptoms 3
• As a shared decision between patient and clinician 3

Levothyroxine monotherapy should remain first-line treatment for newly diagnosed hypothyroid patients, as it has been the standard of care for over 40 years. 2, 5

Critical Pitfalls to Avoid

• Never start liothyronine as first-line therapy for newly diagnosed hypothyroidism—levothyroxine remains the treatment of choice 2
• When switching from levothyroxine or other thyroid preparations, discontinue the other medication first, initiate liothyronine at low dosage, and increase gradually, bearing in mind residual effects may persist for several weeks 1
• Transient hypertriiodothyroninemia with combination doses is unlikely to exceed reference range but requires monitoring 2
• Individual clinicians should not feel obliged to continue liothyronine started by others if they judge it not in the patient's best interest 3