Liothyronine
Liothyronine
Generic Name
Liothyronine
Mechanism
Liothyronine (C15H12I2NO4) is the active synthetic form of the thyroid hormone T3 (triiodothyronine).
• Receptor binding: Diffuses through cell membranes, binds to cytosolic and nuclear thyroid hormone receptors (TRα and TRβ).
• Gene transcription: Induces conformational changes that recruit co‑activators, enhancing transcription of target genes (e.g., Na⁺/K⁺‑ATPase, creatine kinase).
• Metabolic effects:
• ↑ basal metabolic rate (BMR)
• ↑ oxidative phosphorylation and mitochondrial biogenesis
• ↑ lipolysis, β‑oxidation, and gluconeogenesis
• ↑ protein catabolism via ubiquitin‑proteasome pathway
• Cardiovascular impact: Stimulates β‑adrenergic‑mediated increases in heart rate and contractility, amplifying sympathetic tone.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | ~70 % oral bioavailability | Rapidly absorbed; peak plasma Cmax 4–6 h post‑dose |
| Ext. | Gastro‑intestinal dissolution and minimal first‑pass | Food reduces absorption by ~30 % – administer on an empty stomach |
| Distribution | Volume of distribution ~15 L | Highly protein‑bound (~95 % to albumin & transthyretin) |
| Metabolism | Conjugation (glucuronidation, sulfation) in liver, plus deiodination | Converted mainly to inactive 3,5‑diiodo‑4‑thyronolactone (desiodinated) |
| Elimination | Renal excretion of metabolites | Half‑life ~3–5 h (short, but steady‑state effects last weeks) |
| Drug interactions | ↓ absorption with calcium carbonate, iron salts, sucralfate; ↑ clearance with carbamazepine, phenytoin | Tablets may be delayed or contraindicated in gastric pH‑altering drugs |
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Indications
- Primary hypothyroidism (when levothyroxine alone is insufficient or patient desires rapid T3 effect).
- Specific T3‑sensitive conditions:
- Hypothyroidism with residual hypermetabolism symptoms (e.g., low energy, weight loss).
- Congestive heart failure (rare, off‑label) to augment cardiac output.
- Short‑term adjunct in thyroid hormone replacement for postoperative or post‑ablation “bridge” therapy.
- Experimental: Added to levothyroxine in some studies for depression or migraine reduction (off‑label).
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Contraindications
- Contraindicated in:
- Untreated thyrotoxicosis, known hyperthyroidism.
- Acute coronary syndrome (unstable angina, MI).
- Severe aortic stenosis or severe heart failure.
- Pregnancy (excess exposure can harm fetus), lactation.
- Warnings
- Cardiac risk: Watch for arrhythmias, palpitations, tachycardia.
- Addison’s disease: May precipitate adrenal crisis if untreated.
- Headache, insomnia, anxiety: Dose‑dependent neuropsychiatric effects.
- Bone mineral density: Prolonged T3 can increase bone turnover; monitor in osteopenia.
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Dosing
- Adults (primary therapy):
- Start 5–10 µg once daily; titrate in increments of 5 µg every 2–4 weeks.
- Target goal: TSH 0.5–2.5 mIU/L (if combined with levothyroxine) or free T4/T3 monitoring.
- Switching from levothyroxine: 0.9 µg T4 ≈ 1 µg T3 (total daily).
- Adjunct to levothyroxine: 0.4–0.6 µg T3 added; increase gradually.
- Children: 0.5–1.0 µg/kg/day orally; adjust by serum hormone levels and age.
- Take: First thing in the morning on an empty stomach; separate calcium or iron supplements by 4 h.
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Monitoring
| Parameter | Frequency | Target / Goal |
| Serum TSH | Every 6‑8 weeks after dose change | 0.5–2.5 mIU/L (combination) |
| Free T4 | Every 6‑8 weeks | 0.8–1.8 ng/dL |
| Free T3 | Every 6‑8 weeks (if T3‑only) | 3.0–6.0 pg/mL |
| Cardiac | Baseline ECG, follow‑up if symptoms | Sinus rhythm, no arrhythmia |
| Cognitive/psychiatric | Clinical assessment | No worsening anxiety/depression |
| Bone density | Baseline in patients >50 yr or osteopenia | DEXA T‑score maintained |
| Adrenocortical function | In concurrent steroids or adrenal disease | Hydrocortisone dose adjusted if necessary |
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Clinical Pearls
- Timing matters: Liothyronine peaks rapidly; take in the morning to mimic natural circadian rhythm and reduce insomnia.
- Food interaction: Calcium or iron chelate the drug; use a 4‑hour window.
- Dose titration: Incremental 5 µg steps because T3 has a quick half‑life; allows fine tuning of symptoms before cumulative effects accrue.
- Trial with levothyroxine: When adding T3 to levothyroxine, decrease the latter’s dose by approx. 10 % to offset the metabolic boost from T3.
- Heart‑healthy: In patients with coronary disease, monitor pulse/heart rate closely; consider lower starting doses (3–5 µg).
- Pediatric disadvantage: Liothyronine is not FDA‑approved for children; its high potency and short half‑life make dosing imprecise. Prefer levothyroxine with, or without, a low‑dose liothyronine in selective cases under pediatric endocrine care.
- Endocrine feedback loop: High plasma T3 suppresses CRH → ACTH → cortisol; patients on high‑dose T3 should undergo morning serum cortisol testing if symptoms of adrenal fatigue arise.
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