**6. Medical treatment**

There are three ways by which GD is treated. One is by oral treatment with antithyroid drugs which reduces synthesis of thyroid hormones second is Radioactive iodine ablation where radioactive iodine is used to burn thyroid follicles and third one being thyroid surgery where thyroid gland is removed so that thyroid synthesising machinery is taken outside the body [20, 24]. ATD represent the most commonly used therapy in Europe, Asia, and in the meantime in the USA [25, 26]. The main ATD are thionamides, such as propylthiouracil (PTU), carbimazole (CBZ), and the active metabolite of the CBZ as, methimazole (MMI). CBZ is not an active substance; it has to be decarboxylated to MMI in the liver. Thionamides inhibit the coupling of iodothyronines and hence reduce the biosynthesis of TH [27]. These drugs mainly inhibit function of thyroperoxidase, reducing oxidation and the organification of iodide. ATD are indicated as a first-line treatment of GD, particularly in younger subjects, and for short-term treatment of GD before definitive RAI therapy or thyroidectomy [20]. ATD also helps to reduce TRAb levels and rates of remission of GD. PTU at very high doses also inhibits deiodination of T4 to T3 [28]. However, this effect is of use in case of thyrotoxicosis crisis but for long term use

this effect is not of much use. The starting dose of MMI is usually 10–30 mg daily in divided doses depending on the severity of hyperthyroidism (CBZ 15–60 mg/ day). PTU is given 100 mg every 8 h. titration regimen is used through the Corse of disease, means as disease goes in remission, dose is gradually reduced based on severity of the illness. Thyroid function tests are reviewed 3–4 weekly intervals after initial treatment, and the dose is titrated based on T4 and T3 levels. TSH values remain suppressed for long time hence more reliable is T3 & T4 reports but measuring T4 does add value to report as sometimes overtreatment increases TSH values in short span. The usual daily maintenance doses of ATD in the titration regimen are 2.5–10 mg of MMI and 50–100 mg of PTU. Some have also advocated block and replacement regimen to avoid severe hypothyroidism during treatment where MMZ in dose of 30–50 mg daily along with thyroxin replacement is used throughout the Corse but side effects of ATD are more with this kind of regimen [28].

## **6.1 Adverse events**

Common side effects of ATD are allergic reactions which include rash, urticaria, and arthralgia (1–5%). Minor cutaneous reactions are managed with antihistaminics without stopping the ATD. Substituting an ATD may also be helpful [28]. In the case of a serious allergic reaction like hepatitis, a lupus-like syndrome, and agranulocytosis (neutrophil count <500/mL), which occurs in 0.1–1.0% of cases, it's better to avoid ATD in patients as risk of severity of allergic reaction may increase and it's better to use alternative ways of treatment [29]. Agranulocytosis may occur abruptly within 3 months after the initiation of ATD therapy [30]. The risk of ATD-induced agranulocytosis and pancytopenia at 100 and 150 days after the initiation of ATD was 0.28 and 0.29%, respectively [31].
