34. THYROID AND ANTITHYROID DRUGS

Introduction

The thyroid gland secretes three major hormones – thyroxine (T4), triiodothyronine (T3) and calcitonin. T3 and T4 regulate metabolism, growth and development. Calcitonin helps regulate calcium levels. Low thyroid hormone levels cause hypothyroidism (cretinism in children, myxoedema in adults), whereas excess hormone causes thyrotoxicosis. Thyroid function is controlled by TSH from the anterior pituitary through a feedback mechanism.

Synthesis of Thyroid Hormones

  1. Iodide trapping: Iodide enters follicular cells through sodium–iodide symporter.
  2. Oxidation and iodination: Peroxidase converts iodide to iodine, which attaches to tyrosine residues to form MIT and DIT.
  3. Coupling: Two DIT form T4; one MIT + one DIT form T3.
  4. Release: TSH stimulates endocytosis and breakdown of iodinated thyroglobulin, releasing T3 and T4.
  5. Peripheral conversion: T4 is converted to T3 in liver and kidney. This is inhibited by propylthiouracil, propranolol, iopanoic acid and glucocorticoids.

Mechanism of Action of Thyroid Hormones

Thyroid hormone action resembles that of steroid hormones. T3 binds to nuclear receptors, activates gene transcription and increases protein synthesis. Most T4 converts to T3 inside cells before binding.

Preparations

  • Levothyroxine (T4): oral tablets and IV form
  • Liothyronine (T3): oral/IV (less commonly used)
  • T3 + T4 combinations

Therapeutic Uses of Thyroid Hormones

1. Cretinism and Myxoedema

Levothyroxine is the drug of choice. Early treatment in infants helps normal growth. Elderly and cardiac patients should start with low doses (12.5–25 mcg/day). Young adults may take 50–100 mcg daily. Therapy aims to normalise TSH levels and is usually lifelong.

2. Myxoedema Coma

A life-threatening emergency. Treatment includes:

  • IV levothyroxine
  • IV hydrocortisone
  • Correction of hypothermia and electrolytes
  • Ventilatory support and antibiotics if needed

3. Benign Thyroid Nodule

T4 may be used to suppress TSH and slow nodule growth.

4. Thyroid Carcinoma

T4 suppression therapy reduces TSH stimulation of tumour cells.

Antithyroid Drugs

These reduce synthesis or release of thyroid hormones and are used in hyperthyroidism, Graves’ disease, toxic nodular goitre and thyroid storm.

Classification

  1. Thyroid hormone synthesis inhibitors (Thioamides): Propylthiouracil (PTU), Methimazole, Carbimazole
  2. Anion inhibitors: Thiocyanates, Perchlorates (rarely used)
  3. Hormone release inhibitors: Iodine and iodides
  4. Thyroid tissue-destroying agent: Radioactive iodine (I-131)
  5. Others: Propranolol, Atenolol, Diltiazem, Dexamethasone

Thioamides (PTU, Methimazole, Carbimazole)

Mechanism of Action

  • Inhibit thyroid peroxidase enzyme
  • Block iodination of tyrosine
  • Inhibit coupling of MIT and DIT
  • PTU additionally inhibits peripheral conversion of T4 to T3

Pharmacokinetics

  • Well absorbed orally
  • Carbimazole converts to methimazole
  • Accumulate in thyroid gland
  • Cross placenta — PTU preferred in first trimester

Adverse Effects

  • Skin rashes
  • Joint pain, fever
  • Hepatitis (more with PTU)
  • Rare but serious: Agranulocytosis (stop drug if sore throat/fever appears)
  • Hypothyroidism (reversible)

Uses

  • Long-term treatment of Graves’ disease or toxic nodular goitre
  • Preoperative control of thyrotoxicosis
  • Combined with radioactive iodine for initial control
  • Thyroid storm (PTU preferred)

Anion Inhibitors

Thiocyanates and perchlorates block iodide uptake into the thyroid gland. Due to toxicity and unpredictable response, they are not used clinically.

Iodine and Iodides

These are the fastest acting antithyroid agents. High-dose iodide inhibits hormone synthesis and release (Wolff–Chaikoff effect). Effect is temporary; escape occurs after a few days.

Uses

  • Lugol’s iodine before thyroid surgery
  • Thyroid storm
  • As a mucolytic (KI)
  • As antiseptic (tincture iodine)
  • Goitre prophylaxis (iodised salt)

Adverse Effects

  • Allergic reactions (angioedema, fever, arthralgia)
  • Iodism (headache, sneezing, eye irritation, swelling)
  • Hypothyroidism
  • Fetal goitre (avoid in pregnancy)

Radioactive Iodine (I-131)

Uses

  • Hyperthyroidism due to Graves’ disease or toxic nodular goitre
  • Thyroid adenoma or carcinoma when surgery is unsuitable

Contraindications

  • Pregnancy
  • Children
  • Lactating women

Advantages

  • Simple outpatient treatment
  • Low cost
  • No surgical risks
  • Permanent cure

Disadvantages

  • Slow onset
  • Neck soreness
  • High incidence of hypothyroidism

Beta-Blockers

Propranolol, atenolol and metoprolol quickly relieve symptoms like tremors, palpitations and tachycardia. Propranolol also inhibits T4–T3 conversion.

Uses

  • Symptomatic control until antithyroid drugs act
  • Thyroid storm
  • Preoperative preparation

Thyroid Storm (Thyrotoxic Crisis)

A severe, life-threatening condition characterised by hyperpyrexia, arrhythmias, vomiting and confusion. Precipitated by surgery, infection, trauma or ketoacidosis.

Treatment

  • Hospitalisation and supportive care
  • IV propranolol or oral once stabilised
  • Propylthiouracil via NG tube
  • Sodium ipodate to block hormone release
  • Hydrocortisone to inhibit T4–T3 conversion
  • Cooling, antibiotics and hydration

Detailed Notes:

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