Liothyronine — Thyroid hormone / T3 replacement
Liothyronine is synthetic T3 (triiodothyronine), the biologically active form of thyroid hormone. While T4 (levothyroxine) is the primary thyroid secretory product, T3 is ~3–4x more potent and mediates most thyroid hormone effects directly at the receptor (TRα, TRβ). Key distinction from T4: liothyronine does NOT require peripheral conversion by DIO1/DIO2 enzymes, making it directly available regardless of deiodinase activity. Clinical applications: (1) Combination T3+T4 therapy for hypothyroid patients who remain symptomatic on levothyroxine despite normal TSH — relevant in Thr92Ala DIO2 polymorphism carriers (~15% of population); (2) T3 accelerated protocol for depression augmentation (STAR*D, TR-AugD studies); (3) T3-only protocols for thyroid cancer in preparation for radioiodine scanning (faster washout than T4). Shorter half-life requires BID/TID dosing.
Overview
This page is part of Hormonaly's evidence-graded compound library. All clinical claims are linked to peer-reviewed sources via our dual-layer citation verification pipeline.
Compound Class
Thyroid hormone / T3 replacement
Mechanism of Action
Liothyronine is synthetic T3 (triiodothyronine), the biologically active form of thyroid hormone. While T4 (levothyroxine) is the primary thyroid secretory product, T3 is ~3–4x more potent and mediates most thyroid hormone effects directly at the receptor (TRα, TRβ). Key distinction from T4: liothyronine does NOT require peripheral conversion by DIO1/DIO2 enzymes, making it directly available regardless of deiodinase activity. Clinical applications: (1) Combination T3+T4 therapy for hypothyroid patients who remain symptomatic on levothyroxine despite normal TSH — relevant in Thr92Ala DIO2 polymorphism carriers (~15% of population); (2) T3 accelerated protocol for depression augmentation (STAR*D, TR-AugD studies); (3) T3-only protocols for thyroid cancer in preparation for radioiodine scanning (faster washout than T4). Shorter half-life requires BID/TID dosing.
Regulatory Status
FDA-approved. Cytomel (brand). Multiple generic forms. Compounded sustained-release T3 available but not FDA-approved.
Evidence Level
Moderate — ATA 2014 rates evidence for T4+T3 combination as 'weak/insufficient'; however, multiple RCTs and the TRUST trial show subset benefit. STAR*D evidence for depression augmentation is robust.