Uploaded on

 

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to like this
No Downloads

Views

Total Views
691
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
22
Comments
1
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide
  • 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.

Transcript

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