Drug Treatment of Thyrotoxicosis
The antithyroid drugs interfere with the manufacture of thyroid hormone in the thyroid cell, but carbimazole may also suppress production of the thyroid stimulating antibodies. The drug of choice is generally carbimazole, but propylthiouracil should be used during pregnancy.
The majority of patients placed on antithyroid drugs will have normal thyroid function tests within four to six weeks and side effects are rare. There is a high relapse rate however, with 45% becoming thyrotoxic again after the first 12 months of treatment, and 20% of the remainder relapsing in each of the subsequent 5 years. Thus only about 50% of patients are cured long-term and need no further treatment, but the rest will need either radioactive iodine or surgery.
Antithyroid drugs (Carbimazole and propylthiouracil)
These drugs may be given in two ways:
1. Titration method: Thionamide dose is individualised, depending on the initial severity of disease and response. An initial divided dose of 10–30 mg daily of carbimazole is usually satisfactory. Response should be assessed after 2–4 weeks and periodically thereafter, with a minimum eventual frequency of every third month.
Initial high doses should be progressively reduced to once-daily maintenance doses of 2.5–10 mg/day. Serum TSH tends to be the last of the thyroid function tests to return to normal, but the antithyroid drug dose should be reduced earlier as the T4 and T3 levels start to fall, to prevent the onset of hypothyroidism ('overshoot').
Occasionally, in very active Graves disease, thionamide therapy can lower serum free T4 level below normal, while free T3 level remains raised, and the patient remains hyperthyroid. Thionamide dose should thus not be reduced on the basis of serum free T4 level alone.
2. Block and replace method: Large doses of antithyroid drugs are given with thyroid hormone. This combined thionamide and thyroxine therapy regimen is useful for patients with unstable hyperthyroidism, in whom small variations in thionamide dose cause major fluctuations in thyroid function, but does not increase the likelihood of long-term remission.
The advantage of this method is that it is an easy regime (40 mg of carbimazole with 100 ug of thyroxine all taken first thing in the morning) although it cannot be used in pregnancy.
Side effects of these drugs are rare and usually trivial, but include:
- Bone marrow damage: This is rare and presents as sore throat, fever and mouth ulcers. If this occurs, the patient must report to hospital immediately and stop the tablets. Recovery of the bone marrow occurs in 2 weeks.
- Rashes, pruritus, or joint swelling are common. If the symptoms are mild then the drug may be continued, but in severe cases the carbimazole should be changed to propylthiouracil or vice versa.
Beta-blockers
These drugs can control most of the symptoms of thyrotoxicosis, especially those of the cardiovascular system, but should not be used in heart failure and are completely contraindicated in patients with a history of asthma.
The drug is useful when combined with antithyroid drugs or radioactive iodine and may be stopped when these treatments have come into effect. Beta-blockade is usually achieved by giving propanolol in a dose of 20-40mg 8 hourly. It can be used to prepare even the most toxic patient for surgery, but the beta-blocker should be continued over the perioperative period and for a week afterwards to cover the 8 day half-life of T4 and prevent the onset of thyroid storm.
Iodine
Iodine itself has a remarkable ability to control thyrotoxicosis, and may be the only available agent when other antithyroid drugs cannot be tolerated. Its effect is short lived but it is useful in patients who are allergic to antithyroid drugs and cannot take beta-blockers.
Seven to ten days treatment with Lugol's iodine (0.5ml three times a day) or potassium iodide tablets will allow the most severe thyrotoxic patient to undergo safe surgery. The effect is short lived however, and there is a small window of opportunity for surgery.