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Drug treatment of Graves'disease

The hyperthyroidism of Graves' disease is treated either by 
1.Reducing the synthesis of thyroid hormone using antithyroid drugs or   
2.Reducing the amount of thyroid tissue with radioiodine (Iodine131) treatment or by thyroidectomy
Antithyroid drugs include
Thionamides such as propylthiouracil, carbimazole and the active metabolite of the carbimazole that is methimazole. 
Effects of these drugs are following
1.Inhibit the function of TPO(thyroperoxidase) 
2.Reduce oxidation and organification of iodide. 
3.These drugs also reduce thyroid antibody levels 
4.They enhance rate of remission. 
Drug dosage
The initial dose of carbimazole or methimazole is usually 10–20 mg given every 8 or 12 h, but after euthyroidism is restored once-daily dosing is possible. 
Propylthiouracil is given at a dose of 100–200 mg every 6–8 h, this drug is given in divided doses are usually throughout the course. 
Lower doses of each drug may suffice in areas of low iodine intake as thyrotoxicosis improves.
Ttitration regimen 
In titration regimen the starting dose of antithyroid drugs can be gradually reduced once euthyroidism is achieved.The titration regimen is often preferred beause of the following
1.To minimize the dose of antithyroid drug 
2.It provides an index of treatment response
Block-replace regimen
Alternatively, high doses may be given combined with levothyroxine supplementation .
The advantage of this regimen is this will avoid drug-induced hypothyroidism. 
Monitoring treatment response
Thyroid function tests and clinical manifestations are reviewed every 3–4 weeks after starting drugs and the dose is titrated based on unbound T4 levels in blood. Most patients do not achieve euthyroidism until 6–8 weeks after initiation of treatment. 
TSH levels often remain suppressed for several months and therefore it do not provide a sensitive index of treatment response
The usual daily maintenance doses of antithyroid drugs in the titration regimen are
2.5mg –10 mg of carbimazole or methimazole
50–100 mg of propylthiouracil
Time taken for remission
Maximum remission rates are achieved by 18–24 months for the titration regimen 
6 months for the block-replace regimen. 
Patients with severe hyperthyroidism and large goiters are most likely to relapse once treatment stops, close follow up is required  in all patients for relapse during the first year after treatment and at least annually thereafter.
The common side effects of antithyroid drugs
Rash, urticaria, fever, and arthralgia (seen in 1–5% of patients).These side effect may resolve spontaneously or after substituting an alternative drug. 
Rare but major side effects include
Hepatitis, an SLE-like syndrome; and,the most important agranulocytosis (seen in <1%).
Antithyroid drug should be stopped and not to be restarted if a patient develops major side effects
Written instructions should be provided regarding the symptoms of possible agranulocytosis (sore throat, fever, mouth ulcers) and the patients should be advised to stop treatment and a complete blood count shoud be checked to confirm that agranulocytosis is not present
Propranolol (20–40 mg every 6 h) or longer-acting beta blockers such as atenolol is given  to control adrenergic symptoms, especially in the early stages of disease.
Beta blockers are especially useful in patients with thyrotoxic periodic paralysis
Anticoagulation should be considered in all patients with atrial fibrillation.Digoxin doses need to be increased in the thyrotoxic state