All three therapeutic options would be effective in the treatment of patients with hyperthyroid conditions like Graves’ disease, whereas patients with toxic adenoma or toxic multinodular goiter should have either radioactive iodine therapy or surgery since these patients rarely go into remission.
ATDs are preferred as primary treatment, whereas definitive therapy is reserved only for patients with persistent or recurrent hyperthyroidism. Additionally, patients are given β blockers for the relief of the symptoms of thyrotoxicosis.
The antithyroid drugs are propylthiouracil, thiamazole, and carbimazole. All are actively transported into the thyroid where they inhibit iodide oxidation by inhibiting thyroid peroxidase and the coupling of the iodotyrosines to synthesize T4 and T3. These drugs might also have anti-inflammatory and immunosuppressive effects.
Thiamazole has several advantages over propylthiouracil, such as better efficacy, longer half-life, and duration of action once-daily dosing compared with two to three times daily dosing of propylthiouracil; and less severe side-effects.
Reports of liver damage in patients who had received propylthiouracil prompted the US Food and Drug Administration to reassess the role of propylthiouracil in the management of treatment against propylthiouracil as the first-line therapy.
The starting dose of thiamazole depends on the severity of the hyperthyroidism and the size of the thyroid gland. Mild hyperthyroidism and small glands need 10–15 mg of thiamazole daily, and severe hyperthyroidism and large thyroids need 20–40 mg daily.
The starting dose of propylthiouracil is usually 50–150 mg administered three times daily. Thyroid function should be checked 4–6 weeks after initiation of therapy and then every 2–3 months once the patient is euthyroid although we usually see the patient every 4 months when they are euthyroid.
TSH might remain suppressed for several months, which is why serum T4 and T3 should be monitored to assess the efficacy of therapy. Once euthyroidism is achieved, a maintenance dose of thiamazole of 5–10 mg daily or 50 mg propylthiouracil two or three times daily, or lower, should be continued for 12–18 months, and even longer duration of therapy.
A drawback of ATD therapy is the high rate of relapse of hyperthyroidism after the drug has been discontinued. Relapse is more frequent in the first year than subsequent years, particularly in the first 6 months after stopping the drug, but uncommon after 4–5 years.
Patients at higher risk of recurrence are those with severe hyperthyroidism, large goiter, high T3: T4 ratios, and persistently suppressed TSH.
Minor side-effects of ATDs occur in about 5% of patients. These side-effects include pruritus, arthralgia, and gastrointestinal distress.
Major side-effects of ATDs are rare.
Agranulocytosis, in which the absolute granulocyte count is less than 500 cells/mm³.
Patients usually present with fever or a sore throat, or both, and sometimes with other less common symptoms such as chills, diarrhea, and myalgia. Treatment of agranulocytosis and its associated infections might be also necessary, such as administration of broad-spectrum antibiotics.
Other very rare hematological side-effects of ATDs include aplastic anemia, thrombocytopenia, and hypoprothrombinemia.
Another major side-effect is hepatotoxicity. It usually develops within 3 months of therapy and the incidence peaks in the first 30 days of treatment.
Hepatotoxicity can rarely present as the acute liver failure, which is associated with propylthiouracil more frequently than with thiamazole, and might require the liver transplant.
Vasculitis is a very rare complication that has been reported during therapy with ATDs. Vasculitis is often associated with antineutrophil cytoplasmic antibody and is more frequent in patients taking propylthiouracil than in those taking thiamazole.
Patients might present with fever, arthralgia, and skin involvement, or might have organ failure—mainly of the kidneys and lungs.
Radioactive iodine therapy
Radioactive iodine therapy is safe and cost-effective. Absolute contraindications include pregnancy, breastfeeding, planning pregnancy, and inability to comply with radiation safety recommendations. In patients with thyroid nodules whose biopsy samples are suspicious for or diagnostic of thyroid cancer, radioactive iodine is contraindicated and surgery is recommended.
Management of patients receiving radioactive iodine therapy
Some patients, especially elderly patients and those with comorbidities (in particular cardiovascular complications) or severe thyrotoxicosis, might need pretreatment with ATDs. Some argue that thiamazole pretreatment has no effect on the efficacy of radioactive iodine therapy, but is protective because it lowers baseline thyroid hormone concentrations before radioactive iodine therapy.
Follow-up of patients who receive radioactive iodine therapy:
Thyroid function should be monitored 1–2 months after radioactive iodine therapy. Some suggest measuring free T4 no more than 6 weeks after radioactive iodine therapy, to detect hypothyroidism, especially in patients at risk for developing or worsening Graves’ orbitopathy.
If the patient is still thyrotoxic 1–2 months after radioactive iodine therapy, thyroid function should be monitored every 4–6 weeks until the patient is euthyroid or hypothyroid. Levothyroxine replacement should be started as soon as hypothyroidism occurs. Subsequent monitoring is important because some patients given radioactive iodine might have transient hypothyroidism, followed by the relapse of hyperthyroidism
These patients are usually younger, have larger goiters, and have received pretreatment with propylthiouracil. Patients with relapsed or persistent hyperthyroidism after 6 months can be given radioactive iodine again.
One side-effect is acute thyroiditis. It occurs in 1% of patients, lasts for a few weeks, and is easily treated with non-steroidal anti-inflammatory drugs (NSAIDs) and β blockers for the associated exacerbation of hyperthyroidism. Some patients with severe cases might need glucocorticoids. Cancer incidence is slightly higher in patients who are hyperthyroid than in those who are euthyroid but is not associated with the type of thyroid treatment.
Thyroidectomy is the most successful treatment for Graves’ hyperthyroidism. Thyroidectomy is particularly recommended in patients with the following characteristics: large goiters or low uptake of radioactive iodine (or both); suspected or documented thyroid cancer
Surgical complications are rare. The most frequent complication is hypocalcemia due to permanent hypoparathyroidism, followed by permanent recurrent laryngeal nerve injury. The risk of these complications is lower when thyroidectomy is done by a high-volume thyroid surgeon.
Thyroid disorder is an increasing disorder amongst endocrine diseases in India. The seriousness of thyroid disorders should not be underestimated as can lead to death in a significant number of cases. Allopathic medicines available for the treatment of thyroid disorder are quite effective in the long-term but leads to adverse effects.