Management of Hyperthyoidism Iraj Nabipour Bushehr University of Medical Sciences

1. Management of HyperthyoidismIraj NabipourBushehr Universityof Medical Sciences

2. Hyperthyroidism • Hyperthyroidism is predominantly a disorder in women. • prevalence of approximately 0.6% among women. • Graves' disease is the most common cause of hyperthyroidism

3. Graves’disease • Graves' disease is an autoimmune disorder caused by an antibody that acts as an agonist on the thyrotropin receptor. • Spontaneous remission in 30% • Ophthalmopathy in one third of patients

4. Hyperthyroidism • iodine deficiency, • the prevalence of toxic adenoma and multinodular goiter increases with age, • more common than Graves' disease in older persons

5. Toxic adenoma and multinodular goiter • cause autonomous, unregulated synthesis of thyroid hormone. • mutation in the thyrotropin receptor gene • not associated with ophthalmopathy • not resolve spontaneously • Radioiodine therapy and surgery

6. Untreated hyperthyroidism • atrial fibrillation, cardiomyopathy, and congestive heart failure. • thyroid storm has a mortality of 20 to 50%. • osteoporosis and fracture.

7. Treatment options • Antithyroid drugs (USA) • Radioiodine therapy (Europe and Japan) • Surgery • a trend towards primary pharmacological treatment

8. Outcomes for treatment • 90% patient satisfaction, • no difference in time to euthyroidism, • and similar rates of sick leave for all three. • long-term quality of life to be similar

9. Reasons for Antithyroid drugs • before radioiodine administration and usually before surgery, several weeks of treatment with an antithyroid drug is administered to achieve a euthyroid state. • in Graves' hyperthyroidism for 1 to 2 years, or longer for remission. • Remission of hyperthyroidism is not expected in toxic adenoma or toxic multinodular goiter.

10. Mechanisms of action • inhibit organification of iodide and coupling of iodothyronines, and hence synthesis of thyroid hormones. • Propylthiouracil also inhibits peripheral mono-deiodination of T4 to T3 • immunosuppressive.

11. Methimazole vs PTU • Compliance is better with methimazole (once daily) • propylthiouracil (two or three times a day) • methimazole is now the starting drug of choice • Methimazole is more effective than propylthiouracil at rapid restoration of euthyroidism

12. Starting dose • starting dose of methimazole is 10–20 mg per day. The equivalent dose of propylthiouracil is 50–100 mg twice daily • most patients have a normalised serum concentration of free T4 after 8–12 weeks. • Thyroid function should be assessed initially every 4–6 weeks

13. Follow-up • Serum TSH might remain suppressed for weeks or months after free T4 has normalised, • a rise in serum TSH above the reference range does necessitate a dose reduction. • Once methimazole dose has been reduced to maintenance levels of 5–10 mg per day, biochemical variables can be monitored less frequently (every 2–3 months).

14. Remission • Treatment duration longer than 18 months is not associated with improved rates of remission. • rate of remission of Graves' hyperthyroidism is roughly 30%.

15. Predict low likelihood of remission • more severe biochemical disease, • male • young age (<40 years) • high concentrations of TSHR antibodies • large goitre • smoking

17. PTU • Should no longer be used as first line treatment in adults or children, unless • the patient is in the first trimester of pregnancy • reports side-effects from methimazole, • if radioiodine or surgery is not an option, • thyroid storm

18. β blockers • improves tremor, palpitation, and anxiety • Propranolol, metoprolol, nadolol, and atenolol are all effective. • a long-acting drug is preferable and can be continued until euthyroidism has been restored by antithyroid drugs

20. Radioiodine (131I) • is similarly processed, • its beta emissions result in tissue necrosis, • effectively ablating functional thyroid tissue over the course of 6 to 18 weeks or more.

21. High-risk patients • with antithyroid drugs for several weeks before radioiodine • elderly persons, • underlying cardiovascular disease • severe hyperthyroid symptoms • concentrations of thyroid hormone two to three times as high as the upper limit of the normal range.

22. Pretreatment with an antithyroid drug • may increase the risk of treatment failure with the initial radioiodine dose • propylthiouracil but not methimazole. • Antithyroid drugs are discontinued 2 to 3 days before the administration of radioiodine.

23. Radioiodine • orally as a single dose of 131I-labeled sodium iodide (Na131I) in liquid or capsule form. • three fixed doses in amounts based on gland size as determined by palpation (5, 10, or 15 mCi)

24. Radioiodine • The cell necrosis induced by radioiodine occurs gradually, and an interval of 6 to 18 weeks or longer must elapse before a hypothyroid or euthyroid state is achieved. • During that interval, hyperthyroidism may transiently worsen. • If the patient was pretreated with antithyroid drugs, they may be resumed 3 to 7 days after radioiodine administration

25. Monitoring • at intervals of 4 to 6 weeks. • When thyroid function has normalized, treatment with beta-blockers and antithyroid drugs is stopped and levothyroxine is administered as indicated • Suppression of serum thyrotropin may be prolonged after successful treatment; therefore measurement of free T4 and T3 is essential for several months after radioiodine therapy.

26. Outcome If sufficient radioiodine is administered, hypothyroidism develops in 80 to 90% of patients with Graves' disease; 14% of patients require additional treatment.

28. Contraindications • Absolute contraindications to radioiodine treatment are pregnancy, lactation, and an inability to comply with radiation safety regulations. • Radioiodine is considered safe for use in women of childbearing age and in older children. • Moderately severe ophthalmopathy • Concurrent administration of glucocorticoids mitigates exacerbations, at least in patients with mild ophthalmopathy. • Patients who are allergic to iodinated radiocontrast agents are usually not allergic to radioiodine.

29. Complications • Radiation thyroiditis • In most studies, radioiodine has not been associated with an increased risk of cancer. • at increased risk for death from cardiovascular disease primarily in the first year after treatment.

30. Relative indications for surgery • large goitre (suspicion or diagnosis of coexisting thyroid cancer are absolute indications), pregnancy (if drug side-effects are serious) or desire for pregnancy, and pronounced ophthalmopathy. • Relapse after a course of antithyroid drugs is also a relative indication.

31. Relative indications for surgery • Total thyroidectomy is the preferred surgical approach in view of the relapse rate after partial thyroidectomy • In experienced hands, the rates of permanent hypoparathyroidism and recurrent laryngeal nerve damage are less than 2% and 1%, respectively.

32. Recommendations • Radioiodine, antithyroid drugs, and surgery are all reasonable • Pretreatment with antithyroid drugs should be considered in elderly persons and in patients with underlying cardiovascular disease, severe hyperthyroid symptoms, or thyroid hormone concentrations that are two to three times the upper limit of the normal range. • Surgery, rather than radioiodine therapy, is recommended for patients with active, moderately severe Graves' ophthalmopathy. • Concurrent use of glucocorticoids should be considered in those with active, mild ophthalmopathy and in smokers. • Patients should be returned to the euthyroid state with antithyroid drugs before surgery to avoid thyroid storm.