**7. Laboratory diagnosis**

Diagnosis of Graves' disease can be confirmed by measurement of serum TSH and total thyroxine (TT4) and triiodothyronine (TT3). Serum TSH level is suppressed or undetectable with increased TT4 and TT3 level in patients of Graves' disease. Serum TSH level is the most sensitive test. The free T4 (FT4) and free T3 (FT3) levels are increased more than that of TT4 and TT3. Measurement of FT4 and FT3 are expensive, and there is more chance of laboratory errors. FT4 and FT3 can be measured in conditions associated with high serum TBG level like pregnancy, oral contraceptive use and chronic liver disease. In patients of Graves' disease serum T3 level is proportionately more elevated than the serum T4 level. In upto 12% of patients, especially in the iodine deficient areas, only TT3 or FT3 is elevated with a normal TT4 or FT4 level, a condition known as T3 toxicosis. Conversely in some patients (iodine induced hyperthyroidism, drugs like amiodarone and propronolol which block the conversion of T4 to T3), only TT4 or FT4 is elevated with normal TT3 and FT3 (T4 toxicosis). Serum thyroglobulin level is high in all cases of thyrotoxicosis except factitious thyrotoxicosis.

Thyroid Hormone Excess: Graves' Disease 171

In Graves' disease thyroid tissue typically become hypoechoic because of reduction in colloid content, increase in thyroid vascularity and lymhocytic infiltration. In colour flow doppler there is a distinct pattern characterized by markedly increased signals, inferior thyroid artery and itrathyroidal artery velocities more than 40 cm/s. This pattern, in conjunction with a hypoechoic pattern allows distinction from Hashimoto's thyroiditis.

If a patient presented with diffuse goiter with clinical and biochemical thyrotoxicosis, ophthalmopathy and positive autoimmune markers like anti TPO antibody or TSHR-Ab, diagnosis of Graves' disease is straight forward. In absence of these classical features radionuclide scan (I123, I131, Tc99m) in the most reliable distinguishing test. In case of Graves' disease there is diffuse and high uptake, whereas in patients with toxic adenoma or toxic multinodular goiter there is patchy uptake. In patients with thyroiditis and factitious thyrotoxicosis there is decreased uptake. In patients with TSH producing adenoma, there is also a diffuse goiter, but TSH is inappropriately normal or increased instead of suppress TSH of graves' disease. Panic attacks, mania, pheochromocytoma and malignancy can be

There is no ideal treatment option present targeting the basic pathogenic mechanisms of Graves' disease. Available treatment options target the increased synthesis of thyroid hormones by antithyroid drugs, or ablation of thyroid tissue by surgery or radioiodine. Antithyroid drugs are the predominant therapy in Europe and Japan whereas radioiodine is first line of treatment in USA. No single treatment is optimal and patients often require

Thionamides are the main antithyroid drugs which includes propylthiouracil, carbimazole and methimazole. Thionamides act by inhibiting the enzyme thyroid peroxidase, reducing the oxidation and organification of iodide and coupling of iodotyrosines. Carbimazole is not an active drug, and in body it is converted to active metabolite methimazole. Proylthiouracil, in addition to inhibit thyroid hormone synthesis, also inhibits the peripheral conversion of T4 to T3. Methimazole is ten times more potent than prophylthiouracil. Half life of methimazole is about 6 hours while that of prophylthiouracil is about 90 minutes. Duration of action of methimazole is more than 24 hours while that of propylthiouracil is 12- 24 hours. Transplacental transfer of prophylthiouracil is lowest. Antithyroid drugs do not block the release of preformed hormones, so euthyroidism is not obtained until intrathyroidal hormone store is depleted. These drugs also reduce thyroid antibody level.

**7.2. Thyroid ultrasound** 

**7.3. Differential diagnosis** 

easily ruled out by thyroid function test.

**8. Treatment** 

multiple treatment.

**8.1. Antithyroid drugs** 

Anti TPO antibody can be detected in upto 90%43,44 of patients with Graves' disease whereas anti-thyroglobulin antibody is present in 50-80% cases.45,46 They are useful in confirming the presence of thyroid autoimmunity but they are of limited diagnostic value. TSHR-Ab assay is very sensitive and specific (upto 98%) for the diagnosis of Graves' disease. But TSHR-Ab assay is quite expensive and not widely available. TSHR-Ab assay is indicated only when clinical and laboratory diagnosis are not clear. Indications for TSHR-Ab assay are:


TSHR-Ab assay is also a useful indicator of the degree of disease activity. It can also predict the prognosis of Graves' disease. There is more chance of relapse in patients with persistently high TSHR-Ab level after cessation of antithyroid drug.47

Associated hematological abnormalities include increased RBC mass, leucopenia with relative lymphocytosis, monocytosis and eosinophilia, increased factor VIII level. Other associated abnormalities include elevated liver enzymes, bilirubin and ferritin.
