Thyroid drugs

Definition and Therapeutic Significance

Thyroid drugs are pharmacological agents used to manage disorders of the thyroid gland, which include conditions of hormone excess (hyperthyroidism), deficiency (hypothyroidism), inflammation (thyroiditis), thyroid nodules, and thyroid cancer. These drugs are broadly classified into two categories:

1. Thyroid hormone replacement drugs, used to treat hypothyroidism and prevent recurrence of thyroid cancer.

2. Antithyroid drugs, used to reduce thyroid hormone synthesis or release in hyperthyroidism.

Both categories are essential in restoring and maintaining euthyroid status and preventing complications such as cardiovascular disease, osteoporosis, myxedema coma, and thyroid storm.

---

Classification of Thyroid Drugs

1. Thyroid Hormone Replacement Agents

2. Antithyroid Agents (Thionamides and others)

3. Adjunctive Drugs in Hyperthyroidism

4. Radioactive Iodine and Iodide Preparations

5. Thyroid Diagnostic Agents

---

1. Thyroid Hormone Replacement Agents

These drugs compensate for low or absent endogenous thyroid hormone.

a. Levothyroxine (Synthetic T4)

• Mechanism: Converts to triiodothyronine (T3) in peripheral tissues; binds to nuclear thyroid hormone receptors.

• Indications: Primary hypothyroidism, Hashimoto’s thyroiditis, post-thyroidectomy, thyroid cancer suppression.

• Dosing: 1.6 mcg/kg/day (adults); adjusted based on TSH.

• Brands: Synthroid, Eltroxin, Euthyrox, Eltroxin, Levoxyl, Euthyrox.

• Adverse Effects: Hyperthyroid symptoms (palpitations, insomnia, weight loss), cardiac strain.

• Drug Interactions:

  • Decreased absorption: Calcium, iron, sucralfate, PPIs

  • Increased clearance: Carbamazepine, rifampin, sertraline

  • Enhanced effects: Warfarin (bleeding risk)

b. Liothyronine (Synthetic T3)

• Mechanism: Active thyroid hormone; faster onset and shorter half-life than T4.

• Indications: Rapid replacement in myxedema coma, adjunct in hypothyroidism nonresponsive to T4.

• Brands: Cytomel (U.S.), Tertroxin (U.K.).

• Limitations: Fluctuating serum levels, cardiotoxicity.

c. Desiccated Thyroid Extract (DTE)

• Source: Porcine thyroid gland; contains T3 and T4 in non-physiologic ratios.

• Brands: Armour Thyroid, Nature-Throid.

• Controversy: Lack of standardization; not recommended by major guidelines (e.g., ATA).

---

2. Antithyroid Drugs

Used to reduce thyroid hormone production, primarily in hyperthyroidism and Graves’ disease.

a. Thionamides

i. Methimazole (MMI)

• Mechanism: Inhibits thyroid peroxidase (TPO) → blocks iodine organification and coupling.

• Indications: First-line treatment for Graves’ disease (non-pregnant adults).

• Dosing: 5–30 mg/day depending on severity.

• Advantages: Once-daily dosing; lower hepatotoxicity than PTU.

• Adverse Effects: Agranulocytosis, rash, hepatotoxicity, teratogenicity (1st trimester).

ii. Propylthiouracil (PTU)

• Mechanism: Same as MMI; also inhibits peripheral conversion of T4 to T3.

• Indications: Thyroid storm, first trimester pregnancy, methimazole intolerance.

• Dosing: 50–150 mg TID.

• Adverse Effects: Hepatotoxicity (boxed warning), agranulocytosis, vasculitis.

Monitoring:

• Baseline CBC, liver function tests.

• TSH, free T4 every 4–6 weeks until euthyroid.

b. Potassium Iodide (Lugol’s solution, SSKI)

• Mechanism: Wolff–Chaikoff effect; inhibits thyroid hormone release.

• Indications: Preoperative thyroidectomy prep, thyrotoxic crisis.

• Dosing: Drops daily for 7–10 days.

• Adverse Effects: Iodism (metallic taste, salivary gland swelling), allergic reactions.

---

3. Adjunctive Drugs in Hyperthyroidism

a. Beta-Blockers

• Example: Propranolol 10–40 mg q6h

• Use: Symptomatic control (palpitations, tremor, anxiety)

• Additional Effect: Inhibits peripheral conversion of T4 to T3 (propranolol)

b. Glucocorticoids

• Example: Dexamethasone, hydrocortisone

• Use: Thyroid storm, orbitopathy, T4 to T3 conversion inhibition

---

4. Radioactive Iodine (RAI) and Iodide Preparations

a. Iodine-131

• Mechanism: Selectively destroys thyroid follicular cells via beta radiation.

• Indications: Graves’ disease, toxic nodular goiter, thyroid cancer ablation.

• Route: Oral solution or capsule (single dose).

• Contraindications: Pregnancy, breastfeeding, severe orbitopathy.

b. Thyroid Uptake Scans

• Use: Differentiate causes of hyperthyroidism; assess nodule function.

---

5. Thyroid Diagnostic and Adjuvant Agents

a. Recombinant Human TSH (rhTSH, Thyrogen)

• Use: Stimulate iodine uptake for cancer surveillance

• Form: IM injection prior to radioiodine therapy

b. Perchlorate and Thiocyanate

• Mechanism: Compete with iodide for uptake into thyroid; rarely used due to toxicity.

---

Adverse Reactions and Monitoring Summary

Agent	Common Adverse Effects	Serious Risks	Monitoring
Levothyroxine	Palpitations, anxiety, weight loss	Atrial fibrillation, osteoporosis	TSH, T4 (every 6–8 weeks until stable)
Methimazole	Rash, arthralgia	Agranulocytosis, hepatotoxicity	CBC, LFT, TSH, free T4
PTU	Rash, GI upset	Severe liver injury, vasculitis	CBC, LFT, TSH, free T4
RAI therapy	Radiation thyroiditis, hypothyroidism	Worsening orbitopathy	TSH, thyroglobulin, neck ultrasound

Drug Interactions

• Levothyroxine: Reduced absorption with calcium, iron, bile acid sequestrants; enhanced clearance with enzyme inducers.

• Thionamides: Additive bone marrow suppression with other myelotoxic agents.

• Beta-blockers: Additive bradycardia with digoxin.

• RAI: Discontinued antithyroid drugs before treatment to maximize uptake.

---

Special Populations

• Pregnancy:

  • Hypothyroidism: Levothyroxine is safe and essential; increase dose by 30% on confirmation of pregnancy.

  • Hyperthyroidism: PTU preferred in 1st trimester; methimazole in 2nd and 3rd trimesters.

• Pediatrics:

  • Require weight-based dosing.

  • Monitor growth, development, and TSH regularly.

• Elderly:

  • Initiate thyroid hormone therapy at lower doses due to cardiac sensitivity.

---

Examples of Brands and Generics

Generic Name	Brand Name(s)	Drug Class
Levothyroxine	Synthroid, Euthyrox	T4 Replacement
Liothyronine	Cytomel	T3 Replacement
Methimazole	Tapazole	Antithyroid (TPO inhibitor)
Propylthiouracil	PTU	Antithyroid
Potassium Iodide	Lugol’s, SSKI	Iodide preparation
Propranolol	Inderal	Beta-blocker (symptom control)
Iodine-131	Hicon	Radioactive iodine
Thyrotropin alfa	Thyrogen	Diagnostic agent