T3 / Liothyronine

Active thyroid hormone. FDA-approved for hypothyroidism, myxedema coma, and TSH suppression in thyroid cancer. For a euthyroid 20yo with no symptoms, T3 is net-negative — it suppresses endogenous thyroid axis, accelerates bone loss, and adds CV strain (afib risk, tachycardia) for zero cognitive benefit. Bodybuilding "high-T3 cutting protocols" are an established cause of arrhythmia, muscle catabolism, and post-cycle hypothyroid rebound. Modest TRD adjunct signal exists (STAR*D), but irrelevant absent depression diagnosis.

T3 (3,3',5-triiodothyronine) is the active form of thyroid hormone. T4 (levothyroxine) is a prohormone that the body converts to T3 via deiodinase enzymes (D1/D2) — meaning T4 is the body's slow-release reservoir, while T3 acts immediately.

T3 enters cells, binds nuclear thyroid hormone receptors (TRα and TRβ), and the receptor-hormone complex binds thyroid response elements (TREs) on DNA, modulating transcription of hundreds of genes. The downstream effects:

• Metabolic rate (BMR): ↑ mitochondrial biogenesis, ↑ Na/K-ATPase activity, ↑ uncoupling protein expression — net heat and oxygen consumption rise
• Cardiovascular: ↑ β-adrenergic receptor density on myocardium → ↑ heart rate, ↑ contractility, ↑ cardiac output. This is why hyperthyroidism causes palpitations and afib.
• Protein metabolism: Biphasic — physiologic doses are anabolic (growth-promoting); supraphysiologic doses are catabolic (muscle breakdown, the bodybuilding hazard)
• CNS: TRβ in brain regulates mood, cognition; this is the basis for TRD adjunct use
• Bone: ↑ osteoclast activity → bone resorption → osteoporosis with chronic excess

Compared to T4: T3 has half-life ~2.5 days vs T4's ~7 days, and ~4× higher receptor potency. Cytomel peaks 2-4 hours post-dose, making it harder to dose-stabilize than T4 — this is one reason endocrinologists default to T4 monotherapy for hypothyroidism.