Anterior Pituitary Hormones, Thyroid Hormone and Thyroid Inhibitors

❓ Enumerate the antithyroid drugs. Explain the ac- Ans.

tion of the thioamides giving the indications, advantages

and adverse effects of each of them.

➡Hyperthyroidism is caused due to excess of circulating thyroid hormone.

Drugs used in the treatmen of hyperthyroidism are classified as follows:

i. Thyroid hormone synthesis inhibitors or antithyroid

drugs (thioamides or thiourea derivatives): Propylthio-

uracil, methimazole, carbimazole

ii. Inhibitors of iodide trapping (inhibitors): Thiocyanates

and perchlorates

iii. Hormone release inhibitors: lodine, iodides of Nat and

K and organic iodide

iv. Thyroid tissue destroying agent: Radioactive iodine

v. Others: Propranolol, atenolol, diltiazem, dexamethasone

The mechanism of action of thioamides (thiourea derivatives),

eg. propylthiouracil, methimazole, carbimazole are as follows:

Thioamides act by reducing hormone synthesis.

They inhibit thyroid peroxidase enzyme, which converts

iodide to iodine.

They inhibit iodination of tyrosine residues in thyro-

globulin.

They inhibit coupling of iodotyrosine residues (MIT

and DIT).

Propylthiouracil

Propylthiouracil is less potent and most rapidly absorbed.

It has short half-life and needs to be given every 6-8 h.

It also inhibits the peripheral deiodination of T4 to T3. Other thioamides inhibit this process to a much lesser extent.

Dose: 50-150 mg TDS followed by 25-50 mg BD or

TDS for maintenance

Available as PTU 50 mg

Carbimazole

Carbimazole is a commonly used drug as it is more potent and long acting. Carbimazole acts largely by getting converted to methimazole in the body.

Dose: 5-15 mg TDS initially, maintenance dose is

2.5-10 mg daily in 1-2 divided doses.

Available as Neomercazole, Thyrozol and Antithyrox

5 mg tab.

Adverse Effects

i. Allergic reactions or skin rashes are most common.

ii. Hypothyroidism due to overtreatment is common but

reversible on stopping the drug.

iii. Important side effects are GI intolerance, joint pain,

hepatitis, nephritis, etc.

iv. Rare complications include loss or greying of hair, loss

of taste, fever and liver damage.

v. A less common but most dangerous adverse effect is

agranulocytosis. It is mostly reversible.

Uses

They are used in the long-term treatment of thyrotoxicosis

where surgery is contraindicated or not feasible and radio-

active iodine is contraindicated.

1. Graves disease is diffuse toxic goitre and needs treat-

ment for long term (1-5 years).

ii. Toxic nodular goitre as an altenative when surgery is

not indicated as in elderly patients.

iii. Preoperatively, hyperthyroid patients are made euthyroid with antithyroid drugs and then operated

They are used along with radioactive iodine to hasten

recovery in thyrotoxicosis.

They are used for treatment of thyrotoxic crisis along

with iodide and propranolol.

iv. Thyroid storm or thyrotoxic crisis is sudden, severe

exacerbation of thyrotoxicosis and can be life threatening. Propylthiouracil, oral or rectal potassium iodide,IV hydrocortisone and supportive therapy are needed

immediately.

Advantages

Advantages of antithyroid drugs over surgery or 131I are as

follows:

i. No surgical risks and no chances of injury to parathy-

roids or recurrent laryngeal nerve.

ii. Hypothyroidism, if induced, is reversible.

iii. Can be used in children and young adults also.

Disadvantages

Disadvantages of antithyroid drugs are as follows:

i. Prolonged treatment is needed as relapse rate is high.

ii. Not useful in uncooperative or unintelligent patients.

ii. Drug toxicity