Generic Name

Synthroid

Mechanism

• In‑vitro & in‑vivo: Synthroid is a thyroxine (T4) analogue that enters cells via the OCT4 transporter and is deiodinated to the biologically active triiodothyronine (T3) primarily by type 1 deiodinase in the liver, kidney, and skeletal muscle.
• Receptor Activation: T3 binds to thyroid hormone receptors (TRα & TRβ) in the nucleus, modulating transcription of genes involved in basal metabolic rate, protein synthesis, and cholesterol metabolism.
• Peripheral Conversion: About 80‑90 % of the administered T4 is converted to T3; the remainder retains potency directly on TRs.

Pharmacokinetics

• Absorption: Oral, 70‑80 % bioavailability; peak plasma levels at ~6–8 h (Cmax).
• Distribution: Highly bound (>99 %) to plasma proteins (α1‑acid glycoprotein, transthyretin); crosses the placenta and the blood‑brain barrier.
• Metabolism: Primarily hepatic, via 5′‑deiodination; also glucuronidation and sulfation.
• Elimination half‑life:
• Children: ~4–7 days
• Adults: ~7 days
• Elderly: ~8 days (due to reduced hepatic clearance)
• Excretion: Urine (≈90 %); feces (≈10 %).

Indications

• Primary Hypothyroidism (e.g., Hashimoto thyroiditis, post‑thyroidectomy).
• TSH‑Suppression Therapy in differentiated thyroid carcinoma (papillary or follicular).
• Myxedema or severe hypothyroid states (emergency replacement).
• Congenital Hypothyroidism when combined with iodine supplementation.
• Pre‑operative thyroid hormone stabilization in thyroid surgery candidates.

Contraindications

• Contraindicated
• Untreated thyrotoxic crisis (e.g., thyroid storm).
• Severe, uncontrolled cardiovascular disease (ischemic heart disease, arrhythmias).
• Septic shock or acute heart failure.
• Warnings
• Pregnancy: T4 is crucial for fetal neurodevelopment; discontinue only if truly needed.
• Pediatric: Initiate ≤ 2 weeks after birth only if warranted.
• Scleroderma or other connective‑tissue disorders: May precipitate flares.
• Precautions
• Monitor glucose in diabetics.
• Anticipate electrolyte abnormalities in patients with adrenal insufficiency.

Dosing

• Adults
• *Initial adult dose*: 1.6 µg/kg/day (≈ 21–25 µg for a 70‑kg person).
• *Maintenance*: 12.5‑25 µg daily (for 80‑90 % of patients).
• *TSH‑suppression*: 25‑75 µg daily; adjust based on TSH target (<0.1 mIU/L).
• Children
• 1.6 µg/kg/day; increase to 2 µg/kg/day if free T4 remains low.
• Elderly
• Start at 12.5‑25 µg; titrate slowly (4‑6 weeks intervals).
• Pregnancy
• Increase by ~25 % during the first trimester; revisit quarterly.
• Administration
• Take on an empty stomach 30–60 min before breakfast.
• No concurrent calcium, iron, soy, or PPIs within 4 h.
• If missing a dose, ingest immediately; if close to the next dose, skip and resume the normal schedule.

Adverse Effects

• Common
• GI upset (nausea, diarrhea, abdominal pain).
• Headache, dizziness, fatigue (often resolution with dose adjustment).
• Serious
• Cardiovascular: supraventricular or ventricular arrhythmias, tachycardia, angina, myocardial infarction.
• Cognitive: anxiety, irritability, insomnia, mood changes.
• Metabolic: weight loss, heat intolerance, tremor.
• Endocrine: silent thyroiditis, thyroid auto‑immune flare.
• Rare
• Injection site reaction (rare oral formulations).

Monitoring

Clinical Pearls

• Timing is Key: Even a single missed dose can elevate TSH in patients with tight TSH targets; use an “always‑on” low‑dose maintenance strategy for elderly or CV‑high‑risk patients.
• Drug Interactions Matter: Calcium carbonate, iron hydroxide, and soy products actively bind levothyroxine. Use a >4‑hour separation; consider a 30‑minute pre‑meal administration with water alone.
• Adrenal Insufficiency Watch: In primary adrenal insufficiency, levothyroxine can precipitate adrenal crisis; assess cortisol and consider hydrocortisone before dose escalation.
• ESR/CRP Rise: An abrupt rise in ESR/CRP without infection or thyroid storm may signal silent thyroiditis; hold when critical.
• Pediatric Pharmacokinetics: Younger children (<5 y) have a shorter half‑life; thus, dose intervals can be tapered sooner, but always titrate slowly.

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