Management of Hyperthyroidism

1. Management of Hyperthyroidism • Baylor College of Medicine • Med-Peds Continuity Clinic • Anoop Agrawal, M.D.

2. Epidemiology • Incidence in adults: • 2% of women • 0.2% of men • In children and adolescents: • Seen in 0.02% (1:5000) • Girls:boys ratio 5:1

3. Diagnosis • Clinical features • Confirm with measurement of serum thyrotropin (TSH) and total or free thyroxine (T4) • low TSH, and high T4 • Occassionally, T4 will be normal - T3 should be measured for the possibility of triiodothyronine toxicosis

4. Case 1 • A 27 yo female with the following thyroid function tests: • TSH normal, Free T4 normal, Tot T4 elevated • What are the likely scenarios? • pregnancy, OCPs, inherited increase in TBG

5. Differential Diagnosis • What is the most common cause of hyperthyroidism? • Grave’s Disease • What are the other common causes? • Toxic nodular goiter - single or multiple • Thyroiditis - subacute, silent, postpartum • Iatrogenic

6. Differential Diagnosis

7. Case 2 • A 40 year old woman presents with symptoms of tachycardia, anxiety and jitteriness. Physical exam finds a slightly enlarged thyroid gland. Her serum studies show a low TSH with elevated Free T4. What is your next step? • radioiodine uptake measurement

8. Case 2 continued • Her radioiodine uptake demonstrated diffuse uptake of iodine. What is the diagnosis and what are her treatment options? • Grave’s disease • Tx options: 1) antithyroid medications, 2) radioablation, 3)surgery

9. Antithryoid Drugs • Thionamides • Beta blockers • Inorganic Iodide

10. How are thionamides used? • Thionamides try to cause permanent remission of Grave’s disease. • Mechanism of action: inhibit the organification of iodide and coupling of iodothyrinones • Two main types: Methimazole (MME), Propylthiouracil (PTU)

11. How are thionamides used? • MME is once daily vs. TID for PTU • MME is has a more rapid effect. • Hence, MME is preferred over PTU except in pregnancy because MME can cause .... to the fetus • aplasia cutis congenita

12. Aplasia Cutis Congenita Congenital absence of skin

13. What is their efficacy? • Clinical trials have varied and controversy hangs over various aspects of their use. • Rates of remission has ranged from 10-75%. In the US, only a 30% remission is seen. • Studies with a longer duration of therapy (2 years) had higher rates of remission. • Disadvantage of long term therapy - need of monitoring, and poor compliance

14. Management of Thionamides • Starting dose of MME is 10 to 20mg daily. • MME has a dose dependent response time - the higher the dose, the more rapid the effect • After initiation, follow TFTs in 4 to 6 weeks to adjust dosing. • Use T3 and T4 levels to adjust dose, as TSH levels may remain low for up to several months after T3 and T4 have normalized

15. Management of Thionamides • Monitor for side effects • Agranulocytosis is a dose dependent side effect of MME. For PTU, it is not dose related. • Monitoring involves recognition of clinical signs: fever or sore throat • Routine WBC measurement not needed • Agranulocytosis is an absolute contraindication to drug therapy

16. Other Drugs • β-Blockers: aid in reducing symptoms and signs of disease • some inhibition of peripheral conversion • all agents in this class are effective, hence selecting once a day drugs (i.e. atenolol) may improve compliance • Inorganic Iodide: inhibits release of hormones for a few days to weeks, hence useful for short term therapy, i.e. thyrotoxic crisis

17. Radioiodine Therapy • Mechanism: destroy thyroid tissue to achieve either a euthyroid or hypothyroid state • In the US, over 60% of endocrinologists select radioiodine as first-line therapy for Grave’s disease. • It is the preferred therapy for women desiring pregnancy in the near future. After RAI, they must wait 4-6 months before conceiving.

18. Why RAI for Graves? • Advantages: higher remission rates - 10% will fail first treatment and require a second dose of 131I • Disadvantage: hypothyroidism - is dose dependent • Contraindications: pregnancy (absolute), ophthalmopathy (relative - RAI may cause or worsen this condition)

19. Management with RAI • If pt is on an antithyroid drug, it should be stopped 3-4 days prior to RAI, and resumed 3-4 days after. • However, it is uncertain how drug therapy impacts RAI efficacy. • Post-ablation: common to see radiation thyroiditis - manifested by thyroid pain, tenderness, and swelling. Also, transient worsening of hyperthyroidism for 1-2 wks.

20. Treatment of other causes • Toxic nodular goiter: RAI only!, antithyroid drugs ineffective • RAI destroys the autonomous nodules, leaving remainder of thyroid intact • these patients rarely will become hypothyroid • Painless thyroiditis: resolves within weeks, symptomatic tx with β-blocker sufficient

21. Conclusion • There are various methods to manage Grave’s disease. • Selection of choice will depend upon discussion of risks and benefits with the patient. • Surgery (partial thyroidectomy) is reserved for treatment failures. • Other causes of hyperthyroidism have more clear treatment choices.

22. References • Franklyn, JA. The Management of Hyperthyroidism. NEJM 1994;330:1731-1738. • Ross, DS. Treatment of Grave’s hyperthyroidism. UpToDate 2006.