Mechanism of action
The mechanisms of action are not completely understood. Some scientists believe that anti-thyroids inhibit iodination of tyrosyl residues in thyroglobulin. It is thought that they inhibit the thyroperoxidase catalyzed oxidation reactions by acting as substrates for the postulated peroxidase-iodine complex, thus competitively inhibiting the interaction with the amino acid tyrosine. Propylthiouracil additionally may reduce the de-iodination of T4 into T3 in peripheral tissues.
The most dangerous side-effect is agranulocytosis (1/250, more in PTU); this is an idiosyncratic reaction which generally resolves on cessation of drug. It occurs in about 0.2 to 0.3% of cases treated with antithyroid drugs. Others include granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia, and for propylthiouracil severe, fulminant liver failure. Patients on these medications should see a doctor if they develop sore throat or fever.
Usage in Graves' disease
In Graves' disease, treatment with antithyroid medications must be given for six months to two years, in order to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells.
A randomized control trial testing single dose treatment for Graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups). But generally both drugs are considered equivalent.
A study has shown no difference in outcome for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are an elevated level of thyroid stimulating hormone receptor antibodies (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity 39%, specificity 98%), a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.
- Manna D, Roy G, Mugesh G (2013). "Antithyroid Drugs and their Analogues: Synthesis, Structure and Mechanism of Action". Acc. Chem. Res. 11: 2706–15. doi:10.1021/ar4001229. PMID 23883148.
- Zambrana, J.; Zambrana, F.; Neto, F.; Gonçalves, A.; Zambrana, F.; Ushirohira, J. (2005). "Agranulocytosis with tonsillitis associated with methimazole therapy". Brazilian journal of otorhinolaryngology 71 (3): 374–377. PMID 16446945. 
- Bahn, RS, Burch, HS, Cooper, DS, Garber, JR, Greenlee, CM, Klein, IL, Laurberg, P, McDougall, IR et al. (July 2009). "The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration.". Thyroid : official journal of the American Thyroid Association 19 (7): 673–4. doi:10.1089/thy.2009.0169. PMID 19583480.
- Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A (2001). "Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism". Clin. Endocrinol. (Oxf) 54 (3): 385–90. doi:10.1046/j.1365-2265.2001.01239.x. PMID 11298092.
- Glinoer D, de Nayer P, Bex M (2001). "Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study". Eur. J. Endocrinol. 144 (5): 475–83. doi:10.1530/eje.0.1440475. PMID 11331213.