Treatment Of Graves

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  • Things to consider: Would you change treatment if the patient was male? What if they had a large goitre? They were a smoker? What if the patient was older?
  • 26. Cooper DS. The side effects of antithyroid drugs. Endocrinologist 1999;9:457–76. 27. Pearce SH. Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK. Clin Endocrinol (Oxf) 2004;61(5):589–94.
  • 26. Cooper DS. The side effects of antithyroid drugs. Endocrinologist 1999;9:457–76. 27. Pearce SH. Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK. Clin Endocrinol (Oxf) 2004;61(5):589–94.
  • Treatment Of Graves

    1. 1. The treatment of Graves’ disease: What we do and the evidence behind it. Bijay Vaidya Ali Chakera
    2. 2. Outline <ul><li>Case based discussions </li></ul><ul><li>Review of the evidence </li></ul><ul><li>Cases </li></ul><ul><ul><li>Simple Graves’ disease </li></ul></ul><ul><ul><li>Graves’ disease with eye problems </li></ul></ul><ul><ul><li>Graves’ disease and pregnancy </li></ul></ul>
    3. 3. Case 1 <ul><li>A 43 ♀ presents with symptoms of thyrotoxicosis. </li></ul><ul><li>o/e: Sinus tachycardia Small diffuse goitre No evidence of thyroid eye disease </li></ul><ul><li>TSH <0.01mu/L FT4 45pmol/L (12-24) </li></ul><ul><li>Positive TSH receptor antibodies </li></ul>
    4. 4. What would you do? <ul><li>To discuss: </li></ul><ul><ul><li>What treatment would you offer this lady? </li></ul></ul><ul><ul><li>How long would you treat her for? </li></ul></ul><ul><ul><li>Why have you chosen the option that you have chosen? </li></ul></ul>
    5. 5. What your colleagues do? <ul><li>Locally: </li></ul><ul><li>Nationally: </li></ul>
    6. 6. Preferred treatment options for initial treatment of Graves’ Vaidya et al . Clinical Endocrinology (2008) 68 , 814
    7. 7. What are the questions? <ul><li>Initial treatment </li></ul><ul><ul><li>Drugs vs radioiodine vs surgery </li></ul></ul><ul><li>Optimal drug treament </li></ul><ul><ul><li>CBZ vs PTU </li></ul></ul><ul><ul><li>B&R vs Dose titration </li></ul></ul><ul><ul><li>Duration of treatment </li></ul></ul><ul><li>On what basis should we be treating? </li></ul><ul><ul><li>Most effective? </li></ul></ul><ul><ul><li>Most cost-effective? </li></ul></ul><ul><ul><li>Least side-effects? </li></ul></ul><ul><ul><li>Ease of therapy </li></ul></ul><ul><ul><li>Individualised therapy </li></ul></ul>
    8. 8. What should we use as initial treatment?
    9. 9. <ul><li>Short-term efficacy </li></ul><ul><ul><li>Drugs – Cure: 30-50% </li></ul></ul><ul><ul><li>RAI – Cure: 85%-95% </li></ul></ul><ul><ul><li>Surgery – Cure: 100% </li></ul></ul><ul><li>Long-term efficacy </li></ul><ul><ul><li>No significant difference in QoL 14-21 years after randomisation to antithyroid drugs, RAI or surgery (Abraham-Nordling et al. Thyroid. 2005; 15(11): 1279-86) </li></ul></ul>Efficacy
    10. 10. Cost-effectiveness <ul><li>Radioactive iodine Patel et al. Thyroid. 2006; 16(6): 593-598 </li></ul><ul><ul><ul><li>135 patients with thyrotoxicosis 61% - thionamide, 35% - RAI, 4% - surgery </li></ul></ul></ul><ul><ul><ul><li>Cost per ‘cure’ – thionamide (73%), surgery (100%), RAI (95%) </li></ul></ul></ul><ul><li>Qari et al. Saudi Medical Journal. 2001; 22(10): 907-9 </li></ul><ul><ul><ul><li>100 patients – retrospective Cost per ‘cure’ – thionamide (11%), surgery (54%), RAI (96%) </li></ul></ul></ul>Thionamide £3763 RAI £1375 Surgery £6551 Thionamide £21800 RAI £275 Surgery £6500
    11. 11. Side-Effects/Problems <ul><li>Thionamides </li></ul><ul><ul><li>Common </li></ul></ul><ul><ul><li>Agranulocytosis </li></ul></ul><ul><ul><li>Hepatitis </li></ul></ul><ul><li>RAI </li></ul><ul><ul><li>Short-term restrictions </li></ul></ul><ul><ul><li>Long-term hypothyroidism </li></ul></ul><ul><li>Surgery </li></ul><ul><ul><li>Hypocalcaemia </li></ul></ul><ul><ul><li>Larygeal nerve palsy </li></ul></ul>
    12. 12. What is the best drug therapy?
    13. 13. Medical Treatment <ul><li>Which drug is best </li></ul><ul><li>B&R versus Dose Titration </li></ul><ul><li>Duration of treatment </li></ul>
    14. 14. Which drug? <ul><li>Efficacy </li></ul><ul><li>Side-effects </li></ul><ul><li>Ease of regime </li></ul>
    15. 15. Which drug? <ul><li>Efficacy </li></ul><ul><ul><li>No clear difference between drugs </li></ul></ul><ul><ul><li>Nakamura et al . JCEM. 2007; 92: 2157-62 </li></ul></ul><ul><ul><ul><li>PTU vs MMI: MMI – normalises T4 quicker </li></ul></ul></ul>
    16. 16. Normalisation of FT4 with MMI and PTU
    17. 17. Which drug? <ul><li>Side effects </li></ul><ul><ul><li>CBZ has a more favourable side-effect profile </li></ul></ul><ul><ul><ul><li>CBZ – rash 7% </li></ul></ul></ul><ul><ul><ul><li>Methimazole – rash 12% </li></ul></ul></ul><ul><ul><ul><li>PTU – rash and hepatotoxicity (Cochrane) </li></ul></ul></ul><ul><ul><li>Reports of equal side effects (Cooper 1999, Pearce 2004) </li></ul></ul><ul><ul><li>Recent concerns of hepatotoxity with PTU (Cooper 2009) </li></ul></ul>
    18. 18. <ul><li>Higher side effects particularly hepatotoxicity with PTU. </li></ul><ul><li>American data re: hepatotoxicity of PTU </li></ul><ul><ul><li>33 reports of severe liver failure. </li></ul></ul><ul><ul><li>16 liver transplants (1990-2007) </li></ul></ul><ul><ul><li>US est. 1-2 of 15 000 PTU users develop liver failure. </li></ul></ul>The problems of PTU
    19. 19. Which drug? <ul><li>Efficacy </li></ul><ul><ul><li>No clear difference between drugs </li></ul></ul><ul><li>Side-effects </li></ul><ul><ul><li>CBZ has a more favourable side-effect profile </li></ul></ul><ul><li>Ease of regime </li></ul><ul><ul><li>Once daily dosage of CBZ versus PTU </li></ul></ul>
    20. 20. Which regime? <ul><li>B&R versus Dose Titration (Abrahams et al. Cochrane Reviews 2006) </li></ul><ul><ul><li>Efficacy </li></ul></ul><ul><ul><li>Side Effects </li></ul></ul><ul><ul><li>Ease/convenience </li></ul></ul>
    21. 21. Relapse rates: B&R vs Titration
    22. 22. Side effects: B&R vs titration
    23. 23. B&R versus Dose Titration <ul><li>Efficacy </li></ul><ul><ul><li>No difference in relapse rate (Abrahams et al. Cochrane Reviews 2006) </li></ul></ul><ul><li>Side Effects </li></ul><ul><ul><li>Fewer side effects for dose titration </li></ul></ul><ul><ul><li>However large doses used in B&R trials – up to 100mg/day (Razvi et al . Eur J Endo. 2006; 154: 1-4) </li></ul></ul><ul><li>Ease/convenience </li></ul><ul><ul><li>Fewer blood tests with B&R. Evidence? </li></ul></ul>
    24. 24. Duration of treatment
    25. 25. Duration of Treatment <ul><li>Dose titration </li></ul><ul><ul><li>12 – 18 months optimum </li></ul></ul><ul><ul><li>Higher relapses with 6 months in one study </li></ul></ul><ul><ul><li>No advantage of longer treatment </li></ul></ul><ul><li>Block & replace </li></ul><ul><ul><li>No clear consensus </li></ul></ul><ul><ul><li>6 as good as 12 months in one study. ( Weetman AP et al . QJM. 1994; 87 (6): 337–41) </li></ul></ul>
    26. 26. Radioactive iodine and surgery
    27. 27. Radioactive Iodine <ul><li>Fixed dose vs dose calculation </li></ul><ul><ul><li>Studies suggest no difference in outcome between two options. (Leslie et al. BMJ 2007) </li></ul></ul><ul><ul><li>Dose calculation formulae may under-treat Graves’ (Regalbuto et al. JCEM. 2003) </li></ul></ul><ul><ul><li>Consensus emerging that fixed dose is easier and less time consuming. </li></ul></ul>
    28. 28. Radioactive Iodine <ul><li>Medication peri-therapy </li></ul><ul><li>ATD one week either side of RAI results in higher treatment failure and lower hypothyroidism </li></ul>
    29. 29. Surgery <ul><li>Total thyroidectomy recommended over partial surgery </li></ul><ul><li>Grade A recommendation ( Stalberg et al . W J Surgery) </li></ul>
    30. 30. Heged ü s. Endo & Metab Clinic. 2009
    31. 31. Summary <ul><li>No strong evidence base for any therapy for Graves disease </li></ul><ul><li>RAI – most cost effective. </li></ul><ul><li>CBZ give a chance for cure without long-term therapy </li></ul><ul><li>B&R still the ‘best’ option? </li></ul>
    32. 32. Any thoughts?

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