Thyroid Drugs and Antithyroid Agents

Thyroid Physiology & Regulation - Gland Central Control

• HPT Axis: Hypothalamus secretes TRH (Thyrotropin-Releasing Hormone), stimulating Anterior Pituitary to release TSH (Thyroid-Stimulating Hormone). TSH acts on thyroid gland to produce $T_3$ & $T_4$.
• Regulation:
  • Negative feedback: ↑$T_3$/$T_4$ levels inhibit TRH & TSH secretion.
  • Iodide levels: Essential for hormone synthesis; excess acutely inhibits (Wolff-Chaikoff effect).
• Hormones:
  • $T_4$ (Thyroxine): Major circulating prohormone; converted to $T_3$ peripherally.
  • $T_3$ (Triiodothyronine): More potent, active form; primarily from $T_4$ deiodination.

⭐ Wolff-Chaikoff effect: High iodide acutely inhibits thyroid hormone synthesis (organification) & release. Autoregulatory; escape phenomenon follows.

Hypothyroidism & Thyroid Drugs - Low & Slow Fixes

• Goal: Euthyroid state. Monitor TSH (target 0.5-2.5 mIU/L).
• Levothyroxine (T4): Preferred drug.
  • Oral, daily. Start: 1.6 mcg/kg/day; elderly/cardiac: 12.5-25 mcg/day.
  • Take on empty stomach.
• Liothyronine (T3): Potent, rapid onset, short t½.
  • Uses: Myxedema coma, diagnostic.
• 📌 "Low & Slow": starting dose & titration.

Hyperthyroidism & Antithyroid Agents - Fast & Furious Takedown

• Thioamides: Inhibit thyroid peroxidase (TPO).

  Feature	PTU (Propylthiouracil)	Methimazole (MMI)
  MOA	Inhibits TPO; ↓ peripheral T4→T3 conversion	Inhibits TPO (more potent)
  Uses	Thyroid storm, 1st trimester pregnancy (📌 PTU for Pregnancy & Peripheral)	Preferred (except above)
  Specific ADRs	Hepatotoxicity, ANCA+ vasculitis	Teratogenic (aplasia cutis), cholestasis

• Iodides (Lugol’s, SSKI): Wolff-Chaikoff effect (↓TH synthesis/release), ↓ gland vascularity. Use: Pre-op, thyroid storm. ⚠️ Escape phenomenon.
• Radioactive Iodine ($^{131}I$): Destroys follicles. Dose: 5-15 mCi. CI: Pregnancy. ADR: Hypothyroidism.
• Beta-blockers (e.g., Propranolol): Symptomatic relief (Propranolol 40-80mg q6h in storm); high doses ↓ T4→T3.

⭐ Agranulocytosis (WBC < 500/mm³) is a critical ADR of thioamides (PTU/MMI). Presents with fever, sore throat. Management: Stop drug immediately + G-CSF.

Special Situations & ADRs - Tricky Thyroid Tales

• Thyroid Storm: Life-threatening! ABCs, Propranolol, PTU (preferred, blocks T4→T3), then Iodine (1hr later), Hydrocortisone.

• Myxedema Coma: IV Levothyroxine (300-500 mcg bolus, then 50-100 mcg/day) + IV Hydrocortisone (rule out adrenal insufficiency).
• Antithyroids in Pregnancy/Lactation:

  Drug	Pregnancy	Lactation
  PTU	✅ 1st trimester (MMI teratogenic)	✅ Preferred (low milk transfer)
  Methimazole	✅ 2nd/3rd trimester; ❌ 1st (aplasia cutis)	Monitor infant TFTs

• Key ADRs:
  • Thionamides: Agranulocytosis (⚠️ Sore throat, fever - STOP drug!), rash.
  • PTU: Severe hepatotoxicity (Black Box Warning).

⭐ Amiodarone-Induced Thyrotoxicosis (AIT): Type 1 (↑synthesis, vascular) → Thionamides. Type 2 (destructive, non-vascular) → Steroids.

High‑Yield Points - ⚡ Biggest Takeaways

• Levothyroxine (T4): Drug of choice for hypothyroidism; long half-life.
• Thioamides (Methimazole, PTU): Treat hyperthyroidism by inhibiting thyroid peroxidase.
• PTU: Blocks peripheral T4→T3 conversion; preferred in 1st trimester pregnancy, thyroid storm.
• Methimazole: Generally preferred over PTU (less hepatotoxic), except specific cases.
• Radioactive Iodine (I-131): For thyroid ablation in hyperthyroidism/cancer.
• Beta-blockers: Control hyperthyroidism symptoms (tachycardia, tremors).
• Agranulocytosis: Serious thioamide side effect; monitor fever/sore throat_