Antithyroid agents

Treatment approaches and classification

The treatment of hyperthyroidism (thyrotoxicosis) is based on three main approaches: conservative (pharmacotherapeutic), surgical, and combined. Medical therapy utilizes drugs with various sites of action.

According to their mechanism of action, antithyroid agents are divided into five groups:

1. Destructive to follicular cells: radioactive iodine preparations ($^{131}\text{I}$).
2. Inhibitors of glandular iodine uptake: transport system inhibitors (potassium perchlorate).
3. Inhibitors of hormone synthesis: thiourea derivatives (thiamazole).
4. Inhibitors of TSH production: high-dose iodine preparations.
5. Symptomatic agents: beta-blockers, which do not affect the gland itself but eliminate the manifestations of the disease.

Drugs that inhibit hormone synthesis and iodine uptake

Thiamazole (also known by the synonyms methimazole, mercasolil, and tirozol) acts by blocking the enzyme peroxidase. This leads to the inhibition of tyrosine iodination and, consequently, to a decrease in the synthesis of the main thyroid hormones — triiodothyronine (T3) and thyroxine (T4). The drug is prescribed for oral administration in diffuse toxic goiter. It is important to note that the use of thiamazole during pregnancy and lactation is strictly limited. During this period, propylthiouracil becomes the drug of choice. Its main advantage is that it binds more strongly to blood plasma proteins and crosses the placental barrier significantly less.

Potassium perchlorate works differently: it inhibits the ability of the thyroid gland to capture and accumulate iodine. The mechanism is based on the drug competing with ionized iodine for follicular cell transport systems. Potassium perchlorate is administered orally for mild to moderate forms of toxic goiter, and the course of therapy can last up to 12 months.

Both drugs have a number of serious side effects. Thiamazole can cause dyspeptic disorders (nausea, vomiting). Potassium perchlorate is characterized by high toxicity, particularly hepatotoxicity. Both groups are characterized by hematotoxicity — suppression of hematopoiesis, which can manifest as leukopenia, thrombocytopenia, agranulocytosis, and aplastic anemia. In addition, due to the decrease in hormone levels via negative feedback, these agents exert a goitrogenic effect (provoke a compensatory increase in goiter size).

Radioiodine therapy and supportive pharmacotherapy

Radioactive iodine preparations ($^{131}\text{I}$) are positioned as "first-line" agents abroad. After administration, the isotope is actively captured by the thyroid gland and incorporated into thyroglobulin. The isotope emits $\gamma$-rays and $\beta$-particles, but it is specifically the $\beta$-particles that exert a pronounced cytotoxic effect on the follicular epithelium, destroying them. The half-life of the isotope is 8 days, but radiation in the body is detected for about two months. The antithyroid effect persists for 1–2 months after a single dose. The outcome of such therapy in 80% of patients is the development of hypothyroidism.

For combination therapy and minimization of side effects, supportive agents are used:

• Inorganic non-radioactive iodine preparations: they inhibit the production of thyroid-stimulating hormone (TSH) by the adenohypophysis. Their clinical significance lies in the prevention of the goitrogenic effect caused by thiamazole and potassium perchlorate.
• Beta-blockers (represented by propranolol): while not true antithyroid drugs, they exert a sympatholytic effect. Their goal is the relief of thyrotoxicosis symptoms. They effectively eliminate tremor, tachycardia, arrhythmias, and agitation. Propranolol is actively used for preoperative preparation of patients and to reduce symptoms during radioactive iodine therapy.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The mechanism of development of the goitrogenic effect via the negative feedback principle.
• Hematotoxicity of antithyroid drugs: pathogenesis of agranulocytosis and aplastic anemia.
• Pharmacokinetics of radioactive iodine and principles of radiation safety.
• Features of preoperative preparation of patients with thyrotoxicosis.

Other topics in the section "Hormone preparations, their synthetic substitutes, and antagonists"

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