What is an LT3 (Liothyronine) preparation?

What is an LT3 Preparation?

LT3 (liothyronine) is a synthetic form of the thyroid hormone triiodothyronine (T3), available as liothyronine sodium tablets in doses of 5 mcg, 25 mcg, and 50 mcg, used primarily as a substitute for levothyroxine during thyroid cancer preparation procedures or in combination therapy for hypothyroid patients who remain symptomatic on levothyroxine alone. 1

Chemical Structure and Formulation

• Liothyronine sodium is the synthetic sodium salt form of L-triiodothyronine (L-T3), chemically distinct from the naturally occurring thyroid hormone but biologically equivalent 1
• The preparation contains liothyronine as the active ingredient, with inactive ingredients including calcium sulfate, microcrystalline cellulose, hypromellose, talc, and colloidal silicon dioxide 1
• 25 mcg of liothyronine is approximately equivalent to 1 grain of desiccated thyroid or thyroglobulin and 0.1 mg of levothyroxine (L-thyroxine) 1

Available Dosage Forms

• 5 mcg tablets (debossed with "5" and "220") 1
• 25 mcg tablets (scored and debossed with "25" and "222") 1
• 50 mcg tablets (scored and debossed with "50" and "223") 1

Pharmacokinetic Properties

• LT3 reaches maximum serum concentration (Tmax) at approximately 1.8 hours after oral administration 2
• The drug exhibits a two-compartment pharmacokinetic model with a rapid distribution phase (half-life of 2.3 hours) and a slow elimination phase (half-life of 22.9 hours) 2
• Standard immediate-release LT3 produces a characteristic serum T3 peak at 2 hours, returning to basal levels by 24-36 hours 3

Clinical Applications

Thyroid Cancer Preparation

• LT3 serves as a substitute for levothyroxine (LT4) in thyroid cancer patients during preparation for radioiodine ablation or diagnostic whole body scans 2
• The typical substitution ratio is 1:3 mcg/mcg (LT3:LT4), administered three times daily for at least 30 days before nuclear medicine procedures 2

Combination Therapy for Hypothyroidism

• For patients remaining symptomatic on LT4 monotherapy despite normalized TSH, combination therapy with LT4+LT3 can be considered on a trial basis 4
• The recommended starting approach involves reducing the LT4 dose by 25 mcg/day and adding 2.5-7.5 mcg liothyronine once or twice daily 4
• The recommended LT4/LT3 ratio ranges from 13:1 to 20:1 5
• Approximately 5-10% of hypothyroid patients remain symptomatic despite achieving target TSH levels on LT4 alone, and these patients may benefit from LT3 addition 5

Important Clinical Considerations

Dosing Strategy

• Twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase serum T3 concentration without significant peaks above the reference range 2
• The goal of combination therapy is to achieve a physiological ratio of free T3/free T4 (FT3/FT4) while maintaining non-suppressed TSH 5

Safety Profile

• Transient episodes of hypertriiodothyroninemia with recommended doses of LT4 and LT3 are unlikely to exceed the reference range and have not been associated with adverse drug reactions 4
• Trials following almost 1000 patients for nearly 1 year indicate that LT4+LT3 therapy can restore euthyroidism while maintaining normal serum TSH, similar to LT4 monotherapy 4
• An observational study of 400 patients with mean follow-up of approximately 9 years showed no increased mortality or morbidity risk from cardiovascular disease, atrial fibrillation, or fractures after age adjustment compared with patients taking only LT4 4

Comparison with Other Thyroid Preparations

• Unlike desiccated thyroid extract (DTE), which contains a fixed LT4/LT3 ratio of approximately 4:1 and requires a mean daily dose containing approximately 11 mcg T3 to normalize TSH, synthetic LT3 allows for more precise dosing adjustments 4
• Patients on LT4 replacement alone show the highest rates of elevated reverse T3 (20.9%), while those on preparations containing LT3 demonstrate the lowest reverse T3 levels 6

Emerging Formulations

• A metal-coordinated form of LT3 known as poly-zinc-liothyronine (PZL) exhibits approximately 30% lower peak concentration (Cmax) that is delayed by 1 hour and extends into a plateau lasting up to 6 hours, followed by sustained levels exceeding ½ of Cmax at 24 hours 3
• PZL avoids the typical T3 peak seen after oral administration of standard LT3, potentially providing more stable serum T3 levels 3

Clinical Pitfalls to Avoid

• Fixed-dose LT3 therapy without individualized adjustment can result in supraphysiologic T3 levels 2
• Newly diagnosed hypothyroid patients should be treated with LT4 monotherapy first; LT3 combination therapy should only be considered for patients who have unambiguously not benefited from LT4 alone 4
• There is currently no evidence-based guide for identifying which hypothyroid patients will benefit from LT3, though polymorphism of the deiodinase 2 (D2) genes may predict better response to combination therapy 5