ncbi.nlm.nih.gov/pmc/articl...
Whilst I don't agree especially with the cost effectiveness bits comparing ATD therapy to RAI or TT, this piece is chocked full of details about ATD, RAI, TT. Worth a read since many of us always wonder how long we can go on with Graves on ATD therapy.
I highlight below, the parts pertaining to ATD therapy.
The goals of treatment in Graves’ disease have been an efficient control of symptoms, restoration of euthyroidism, with least adverse effects ...
Most treated patients in Graves’ disease eventually go on to develop hypothyroidism regardless of the treatment modality used.
This awareness of inevitable hypothyroidism with Graves’ disease has led to a change in the objective of treatment. Previously, therapies were selected with the goal of achieving euthyroidism. Instead, hypothyroidism is now the goal of treatment, to ensure that hyperthyroidism does not recur.
The ATDs used belonged to thionamide class and includes methimazole (MMI), carbimazole, and propylthiouracil (PTU).
Maximum clinical response occurs after a latent period of 4-6 weeks and ATD therapy should be continued for a period of 12-18 months after achieving euthyroidism.
A major clinical drawback of ATD therapy is the high rate of relapse seen after discontinuation of therapy.
Irrespective of the treatment duration, the best long-term remission rate achieved with the use of these drugs alone is about 40-50%.[2,3] These rates are even lower in children's, men, older patients, smokers, those with large goiters, and more active disease.
Prolonged drug therapy has not been shown to increase the likelihood of lasting remission. (Questionable)
No difference in remission rates have been seen in subjects treated with for 24 versus 12 months[4] or 42 versus 18 months.[2]
Weetman reviewed prospective trials comparing different duration of treatment and showed that remission rates are not improved with ATD therapy beyond 18 months in adults.[5]
In cases of relapse with an ATD, there is little chance that a second course of treatment will resul t in permanent remission.
High recurrence rate seen with ATD therapy necessitates prolonged ATD therapy, which decreases the cost-effectiveness of therapy because of the need of repeated clinic visits, thyroid function testing, and cost of drug.
These factors promote poor drug compliance, especially in children who need prolonged ATD therapy.
Recurrent untreated hyperthyroidism causes deterioration in the quality of life and may increase morbidity particularly in the elderly who are at risk for conditions like atrial fibrillation.
Hence, need arises of more definitive treatment modalities for toxic Graves’ disease that are focused on “cure” of the disease and create a stable situation earlier in the course of therapy.
Not only this, use of ATD therapy has been associated with various side effects.
Mild side effects, occurring in 20% of the patients, include: Skin reactions, arthralgias, gastrointestinal symptoms, abnormal sense of taste, and occasional sialadenitis.
The serious side effects include agranulocytosis, fulminant hepatic necrosis, and antineutrophil cytoplasmic antibody (ANCA) positive vasculitis; and these can happen anytime during the course of therapy.
Agranulocytosis occurs in 0.1-0.3% of patients and elderly patients and those at higher doses are at higher risk.
Discontinuation of therapy is needed if symptoms such as fever, sore throat or mouth ulcers should develop or absolute neutrophil count falls to less than 1,500 cell/μl.[8]
PTU has been associated with fulminant hepatic necrosis and is the third most common cause of drug related liver failure, accounting for 10% of the entire drug related liver transplantations. The hepatotoxic drug effect can continue despite drug discontinuation and can be fatal.
Vasculitis positive for ANCAs has also been reported as a rare complication of PTU use.[10]
MMI is associated with cholestasis rather than hepatic necrosis.
Steven-Johnson syndrome is another life-threatening complication observed with MMI use in children.
Many times hyperthyroid subjects taking ATDs conceive and then issue of teratogenicity with the use of ATDs during pregnancy comes.
MMI has been associated with aplasia cutis, a localized defect of the skin on the vertex of the scalp and with other congenital anomalies such as esophageal and choanal atresia.[11]
PTU is therefore preferred over MMI or carbimazole during pregnancy.
High doses of PTU in pregnant women, on the other hand expose the fetus to the risk of fetal hypothyroidism.[12]
Examination of 31 cohort studies identified adverse effects of ATDs in 692/5,136 (13%) patients. These were more common with MMI, mainly owing to dermatologic complications, while hepatic effects were more common with PTU use.
In conclusion, the high relapse rate and not so rare fatal side effects seen with ATD therapy compel us to consider other definite modes of treatment for toxic Graves’ disease.
What is the prognosis for someone with Graves’ disease?
Graves Disease the challenge 
