**8.1. Antithyroid drugs**

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.

Antithyroid drugs can be used as a primary treatment or as a preparatory treatment before radioiodine or surgery. The antithyroid drugs are usually started in higher doses. The starting dose of methiomazole or carbimazole is 10-20 mg every 8-12 hours and that of propylthiouracil is 100-200 mg every 6-8 hours. Once euthyroidism is achieved which usually takes 4-5 weeks, methimazole can be given in single daily dose while propylthiouracil is given in multiple daily doses throughout the treatment. There are two treatment strategies for using antithyroid drugs. In titration regimen, antithyroid drugs are started in high doses and dose can be gradually decreased to maintain euthyroid state. In Block and Replace regimen, the antithyroid drugs are maintained in high doses and subsequently levothyroxine is added to maintain the euthyroid status. At present there is no proven advantage of block and replace regimen over titration regimen.

Thyroid Hormone Excess: Graves' Disease 173

iodine is inhibition of hormone release. Iodine also decreases the vascularity of thyroid gland. All of these effects of iodine are transient and lasts only for a few days or weeks. Now a days iodine is used only for preoperative preparation for Graves' disease and in the management of thyrotoxic crisis. The usual dose of Lugol's solution is 3-5 drops three times per day and that of SSKI is 2-3 drops twice daily. Iodine decreases the effect of subsequently

Iodinated radio contrast agents like iopanoic acid, and sodium ipodate acts by blocking the peripheral conversion of T4 to T3 and inhibition of hormone release. They are ideally used in emergency situations when rapid control of thyrotoxicosis is needed or in preoperative

Lithium also acts as a thyroid constipating agent (block the release of thyroid hormones). Lithium also potentiates the beneficial effect of radioiodine. The usual dose of lithium is 450- 900 mg per day in divided doses. Serum lithium concentration should be maintained at

Dexamethasone in high doses (8mg/day) decreases the T4 secretion by the thyroid gland, inhibit the peripheral conversion of T4 to T3, and has immunosuppressive effect. Effect on peripheral conversion of T4 to T3 is additive to propylthiouracil. Glucocorticaids are

β- blockers do not affect the synthesis or secretion of thyroid hormones. Many of the symptoms & signs of thyrotoxicosis are due to hypersensitivity of the sympathetic nervous system to thyroid hormones. Thus use of β- blockers in thyrotoxicosis, improve the signs and symptoms mediated by the sympathetic nervous system. Tachycardia, palpitation, tremor, anxiety, excess sweating, lid retraction improves with β- blockers. Propranolol has additional advantage over other β- blockers. It inhibits the peripheral conversion of T4 to T3. β- blockers reduce cardiac output without altering oxygen consumption, can have adverse effect in liver, where the arteriovenous oxygen difference is already elevated in the hyperthyroid state. Propranolol is most commonly used agent but other β- blockers can also be used. It is used in a dose of 20-60 mg every 6-8 hours. Short acting agents like esmolol is used for intravenous purpose. Long acting agents like atenolol or metoprolol are used for prolonged treatment. β- blockers should be rapidly tapered and discontinued once stable

indicated for the treatment of ophthalmopathy, dermopathy and in thyrotoxic crisis.

administad thionamides and radioiodine for severe weeks.

preparation or while awaiting the response of radioiodine.

They act by intititing the transport of iodine to thyroid gland.

1meEq/L. No adverse effects are reported with this dose of lithium.

**8.3. Thiocyanate and perchlorate** 

**8.4. Lithium** 

**8.5. Glucocorticoids** 

**8.6. β- blockers** 

euthyroidism it achieved.

Patient should be reviewed clinically and biochemically after every 3-4 weeks. Dose of antithyroid drugs is adjusted based on the TT4 or FT4 level, as TSH level often remain suppressed for several months. The usual daily maintenance dose of carbimazole or methimazole is 2.5 – 10 mg and that of propylthiouracil is 50-100 mg. When TSH level become normal, it can also be used to monitor therapy. Size of the goiter decreases in about 30-50% of patients during treatment. In remaining patients it may remain unchanged or even enlarge. Increase in goiter size is one of the earliest manifestations of iatrogenic hypothyroidism. The other features are weight gain, lethargy, fatigue and other signs of mild hypothyroidism.

Maximum remission rate with antithyroid drugs is 30-50%, which can be achieved by continuation of the drug for 6-18 months or even longer. Most of the relapses occur within first 3-6 months after discontinuation of drug. Suppressed TSH level below the normal limit is the first signal of relapse even in the presence of a normal serum T4 level. In most of the studies, the relapse rate is 50-80%.48,49 Most important predictor of relapse is goiter size.50 Other factors influencing recurrence of Graves' disease include high TSHR-Ab concentration, large iodine intake, marked residual goiter, short duration of antithyroid drug treatment and previous recurrence. Factors which favor long term remission after therapy include the initial presence of T3 toxicosis, a small goiter, decrease in the size of goiter, and return of TSH to normal during treatment, the return of serum thyroglobulin to normal, and low iodine diet.

Most common side effects of thionamides are pruritus, skin rash, urticaria, fever and arthralgia. These may resolve spontaneously or after substituting another drug. Rare but major side effects are hepatitis, cholestasis, SLE like syndrome, ANCA positive vasculitis and most importantly agranulocytosis. Major side effects occur in less than 1% of patients.Antithyroid drugs should be stopped and not restarted if patient develop major side effects.
