**3. Diagnosis**

Measurement of Free T4/Free T3 and TSH is the initial diagnostic test. In overt hyperthyroidism FT4 and FT3 are elevated but in milder hyperthyroidism FT4 may be normal with only FT3 elevation. TSH R antibody is sensitive (97%) and specific (98%) tool for accurate diagnosis of GD [7]. High resolution ultrasound reveals diffuse goiter and hypoechogenicity. Diagnosis is confirmed by thyroid scintigraphy by Tc 99 pertechnatate or I 123 scintigraphy. Scintigraphy is definitely needed for diagnosis.

### **4. Treatment options**

Anti-thyroid drugs (ATD) are used in the initial management of GD with aim to achieve euthyroidism. Once patient is euthyroid it should be maintained to achieve remission. About half of the patients go into remission after 18 to 24 months of treatment with ATD. Patients without remission and recurrent disease (30–40% in the first 12 months and approximately 50–60% in long term) require definitive therapy. Definitive therapy is either surgical or medical ablation of all thyrocytes. The options are radioactive iodine (RIA) or thyroidectomy. After ablative therapy thyroid hormone replacement is provided to control hypothyroidism. There are reports of use of long term ATD to achieve remission. Choice between RIA and thyroidectomy are influenced by physician, patient, institutional and geographical beliefs and practice patterns. The most "effective" therapy for both physician's and patient perspective will be which will provide rapid euthyroidism and prevent recurrences.

Early and rapid euthyroidism is desirable in all GD patients as it decreases mortality and halts eye disease progression. In a retrospective cohort study of 4189 GD patients regardless of the method of treatment, low TSH at 1 year following GD diagnosis was associated with a 55% increase in cardiovascular mortality (atrial fibrillation, heart failure, pulmonary hypertension, angina pectoris, and stroke) [8]. Lillevang et al. in a cohort study of 235,547 individual investigated association between hyperthyroidism and mortality in both treated and untreated groups and concluded that decreased TSH increases mortality in both groups and with every duration of 6 months of suppressed TSH was associated with 11–13% increase in total mortality [9]. Dale et al. found that even transient hypothyroidism during treatment was associated with greater weight-gain during medical treatment in 162 consecutive hyperthyroid patients [10]. Even consensus statement of the European Group on Graves' orbitopathy (EUGOGO) recommends avoidance of hypothyroidism as it can cause exacerbation of thyroid eye disease [11].

Thyroidectomy is the only modality of treatment which can provide both rapid euthyroidism and prevent recurrence. There are reports of RAI worsening GD ophthalmopathy [12, 13]. In a systematic review of literature between 2001 and 2011which included retrospective and prospective studies (14,245 patients) on the

comparison of RAI and surgery as best definitive treatment for GD, reported surgery to be 3.44 times more likely to be successful than RAI (*P* < .001). And total thyroidectomy (TT) was 95.45 times more successful than RAI (*P* < .001) and concluded thyroidectomy as the most successful modality for the management of GD [14].
