Liothyronine (T3 / Cytomel) — Active Thyroid Hormone — Thyroid Hormones
Active form of thyroid hormone. FDA-approved for hypothyroidism. Narrow therapeutic index requiring careful monitoring.
Overview
Liothyronine sodium (Cytomel, Triostat) is the synthetic form of triiodothyronine (T3), the biologically active thyroid hormone. Unlike levothyroxine (T4), which requires peripheral deiodination to T3 for activity, liothyronine directly activates thyroid hormone receptors (TR-alpha and TR-beta) in target tissues. T3 is approximately 3-5 times more potent than T4 and has a faster onset of action (hours vs days). FDA-approved for hypothyroidism, myxedema coma, and TSH suppression, liothyronine is most commonly used in combination with levothyroxine in patients who remain symptomatic on T4 monotherapy. The American Thyroid Association (ATA) does not recommend routine T3 combination therapy but acknowledges that a subset of hypothyroid patients may benefit, particularly those with polymorphisms in the DIO2 gene that impair T4-to-T3 conversion. Liothyronine has a short half-life (approximately 1 day, vs 7 days for T4), producing fluctuating T3 levels with once-daily dosing and potential symptoms of over- and under-replacement within the same day. For this reason, twice-daily dosing or sustained-release compounded formulations are often preferred. In bodybuilding, liothyronine is misused at supraphysiologic doses (50-100 mcg/day) for fat loss, which carries significant risks including muscle catabolism, cardiac arrhythmia, and thyroid axis suppression.
Indications
- FDA-approved: Hypothyroidism (monotherapy or combination with T4)
- FDA-approved: Myxedema coma (IV formulation)
- FDA-approved: TSH suppression test (diagnostic)
- Off-label: Combination T4/T3 therapy for persistent hypothyroid symptoms
- Off-label: Treatment-resistant depression (augmentation)
- Misuse: Fat loss at supraphysiologic doses (bodybuilding — dangerous)
Mechanism of Action
Liothyronine (T3) directly binds nuclear thyroid hormone receptors (TR-alpha and TR-beta) without requiring deiodination
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Liothyronine (Cytomel) | 5 mcg | Once or twice daily | Starting dose; combination therapy with T4 |
| Liothyronine | 12.5-25 mcg | Divided into 2 doses daily | Typical replacement dose range |
| Liothyronine (sustained-release) | 7.5-15 mcg | Once daily | Compounded SR formulation for stable levels |
| Liothyronine (Triostat) | 25-50 mcg | IV bolus | Myxedema coma — emergency use only |
Evidence Grade
GRADE B
Safety & Contraindications
- Narrow therapeutic index — small dose changes produce significant clinical effects
- Cardiac risk: tachycardia, arrhythmia, angina — especially in elderly and cardiac patients
- Bone loss: excess thyroid hormone accelerates osteoporosis (especially postmenopausal women)
- Muscle catabolism at supraphysiologic doses — counterproductive for body composition
- Short half-life causes T3 level fluctuations — multiple daily dosing may be needed
- Thyroid axis suppression with exogenous use — recovery may be prolonged
- Drug interactions: warfarin, insulin, oral hypoglycemics, cardiac glycosides