Sat 1420-thyrotoxicosis- -seasons

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Sat 1420-thyrotoxicosis- -seasons

  1. 1. 5/23/2014 1 Marshall Dahl MD PhD FRCPC cert Endo Clinical Professor, University of British Columbia marshall.dahl@vch.ca Tel 604 875 5577 Fax 604 875 5188 • Faculty: Marshall Dahl • Relationships with commercial interests: – None – Nada – Nil
  2. 2. 5/23/2014 2 • None CFPC CoI Templates: Slide 2 Not applicable
  3. 3. 5/23/2014 3  Review endocrine physiology of thyroid gland  Five selected types of thyrotoxicosis- understand:  Pathophysiology  Clinical presentation  Investigations  Treatment
  4. 4. 5/23/2014 4  Multiple Etiologies  5 are common  Diagnosis needed for appropriate management  Differentiation can often be made through history and physical examination  23 woman presents for care  Chief Complaint:  “I went to the fitness club and a guy came up to me and said that I should get my thyroid checked!”  “I looked on the internet- I think that it’s overactive!”
  5. 5. 5/23/2014 5  Some findings of thyrotoxicosis are present regardless of the etiology  What symptoms?  What physical findings?
  6. 6. 5/23/2014 6  She wants you to know that her mother and sister have “overactive thyroids”.  She has noticed that her eyes have become more prominent  She’s pretty sure from her reading that she has Graves’ disease  What findings are specific to this condition?
  7. 7. 5/23/2014 7 Weetman, A. P. N Engl J Med 2000;343:1236-1248 Clinical Manifestations of Graves' Disease Pathogenesis of Graves' Disease. Weetman AP. N Engl J Med 2000;343:1236-1248.
  8. 8. 5/23/2014 8 Weetman, A. P. N Engl J Med 2000;343:1236-1248 Bahn, R. S. et al. N Engl J Med 1993;329:1468-1475 Computed Tomographic Scans of the Orbits (Axial Views) in a Patient with Graves' Ophthalmopathy (Panel A) and a Normal Subject (Panel B)
  9. 9. 5/23/2014 9  >60% of cases of thyrotoxicosis  HLA-DR, CTLA-4, but 20% concordance monozygotic twins  Women in North America: 0.5/1000 (20 year incidence)  Women:Men 10:1  Peak: age 40-60, but any age possible Disease Etiology Specific Symptoms Signs Lab Tests Other tests Graves’ TSI Orbitopathy, Dermopathy Firm, rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 TSH receptor antibody* Third generation assay sens 97%, spec 99%. JCEM 98, 6, June 2013, Barbesino
  10. 10. 5/23/2014 10  Radioiodine  Two day procedure  Isotope limited:  Tuesday, Wednesday  Good for etiology  Good for structure  Good if planning iodine therapy  Pertechnetate  Same day procedure  Short notice  Quick result  Good for high uptake  Not good for structure
  11. 11. 5/23/2014 11 Disease Etiology Specific Symptoms Signs Lab Tests Uptake # Pattern Graves’ TSI Orbitopathy, Dermopathy Firm, rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 +ve TSHr Ab High Diffuse
  12. 12. 5/23/2014 12  Contra-indicated in pregnancy and breast- feeding  Can’t be performed in the face of recent radio- contrast dye:  IVP  CT  Angiography  Tracer can’t compete with large exogenous iodine dose for uptake  Kelp pills  57 year old woman  Chief Complaint:  “It’s the worst flu I’ve ever had! I’ve got a fever, I ache all over and I’ve got the worst sore throat and earache!”  “Can I get some antibiotics?”
  13. 13. 5/23/2014 13  “Flu” started with runny nose and cough  Progressed to fever, generalized myalgia, ear pain, pain with swallowing  Thyroid is enlarged, tender, firm, no nodes Pearce, E. N. et al. N Engl J Med 2003;348:2646-2655
  14. 14. 5/23/2014 14 Pearce, E. N. et al. N Engl J Med 2003;348:2646-2655
  15. 15. 5/23/2014 15 Disease Etiology Specific Symptom s Signs Lab Tests Uptake # Pattern Graves’ Disease TSI Orbitopathy, Dermopathy Rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 High Diffuse Sub-acute Thyroiditis Auto- immune+/- viral Pain, tenderness Firm, tender gland ↓ TSH ↑ Free T4 None None  58 year old woman  Symptoms of thyrotoxicosis  Enlarged neck for many years  2010:  TSH 0.1 (0.5-5.5),  Free T4 20 (11-22)  2014:  TSH < 0.01, Free T4 35
  16. 16. 5/23/2014 16  General Appearance: thyrotoxic  HR 100, BP 150/80  Lid-lag, stare, no proptosis  Thyroid asymmetrically enlarged  It is quite firm, irregular, non-tender with no adenopathy
  17. 17. 5/23/2014 17  Worldwide: iodine deficiency  Developed world: genetic and non-immune  Early: diffuse goitre  Later: nodularity  Slow growth with gradual functional “autonomy”- dropping TSH with normal T4  Minority: biochemical and clinical thyrotoxicosis  Some may have local obstructive signs  Avoid exogenous iodine  Jod-Basedow phenomenon  Iodine causes autonomous nodules to overproduce thyroxine  Often older patients  Weight loss, atrial fibrillation, palpitations  No increased risk of malignancy  Biopsy if dominant nodule or increasing size
  18. 18. 5/23/2014 18 Disease Etiology Specific Symptoms Signs Lab Tests Uptake # Pattern Graves’ Disease TSI Orbitopathy, Dermopathy Rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 High Diffuse Sub-acute Thyroiditis Auto- immune+/- viral Pain, tenderness Firm, tender gland ↓ TSH ↑ Free T4 None None Toxic Multi- nodular Goitre “Autonomy” Slow goitre growth Asymmetric, nodular ↓ TSH ↑ Free T4 High Patchy
  19. 19. 5/23/2014 19 Disease Etiology Specific Symptoms Signs Lab Tests Uptake # Pattern Graves’ Disease TSI Orbitopathy, Dermopathy Rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 High Diffuse Sub-acute Thyroiditis Auto- immune+/- viral Pain, tenderness Firm, tender gland ↓ TSH ↑ Free T4 None None Toxic Multi- nodular Goitre “Autonomy” Multifactorial Slow goitre growth Asymmetric, nodular ↓ TSH ↑ Free T4 High Patchy Toxic Nodule TSH receptor mutation Single nodule? Nodule, remainder of thyroid small ↓ TSH ↑ Free T4 High Nodule
  20. 20. 5/23/2014 20  49 year old man with history major depression treated with medication  Improved mood, but weight loss, tachycardia, diaphoresis, tremour  TSH < 0.01  Sertraline  Cytomel  TSH <0.01  Free T4 8 (11-22)  Free T3 9.3 (3.5-6.5)
  21. 21. 5/23/2014 21 Disease Etiology Specific Symptoms Signs Lab Tests Uptake # Pattern Graves’ Disease TSI Orbitopathy, Dermopathy Rubbery gland +/- orbitpathy ↓ TSH ↑ Free T4 High Diffuse Sub-acute Thyroiditis Auto- immune+/- viral Pain, tenderness Firm, tender gland ↓ TSH ↑ Free T4 None None Toxic Multi- nodular Goitre “Autonomy” Multifactorial Slow goitre growth Asymmetric, nodular ↓ TSH ↑ Free T4 High Patchy Toxic Nodule TSH receptor mutation Single nodule? Nodule, remainder of thyroid small ↓ TSH ↑ Free T4 High Nodule Factitious, Iatrogenic Exogenous thyroid hormone History may not be obvious Thyroid not palpable ↓ TSH ↑ Free T4 or T3 None None  Surgery  Sub-total thyroidectomy  Rarely performed  Special cases:  Pregnancy and intolerance of anti- thyroid drugs  <2% recurrence rate  Hypothyroidism common
  22. 22. 5/23/2014 22  Thionamides:  propylthiouracil,  carbimazole and active metabolite methimazole (Tapazole)  Inhibit TPO: reducing oxidation and organification of iodide This image cannot currently be displayed. Methimazole Propylthiouracil Serum Half-life 4-6 hrs 75 minutes Tissue concentration 100X serum (gives 20 hr duration of action) Dosing Single daily 3X/day Time to normalization T3,T4 5.8 weeks 16.8 weeks
  23. 23. 5/23/2014 23  Measure Free T4 monthly (TSH unreliable)  Titrate dose down to maintenance  Maximum remission rate by 18-24 months  Discontinue and monitor for relapse  Methimazole  starting dose: 20-40 mg daily  Maintenance: 2.5-10  PTU  Starting dose: 100-200 TID  Maintenance: 50-100 daily in divided doses  ~4%: rash, urticaria  <3:1,000 agranulocytosis  “Sore throat, high fever- notify physician”  Less common with low dose methimazole  Rarer:  PTU: hepatocellular necrosis  Methimazole: reversible cholestatic jaundice  PTU: vasculitis  Methimazole: scalp defect in neonates
  24. 24. 5/23/2014 24  Either as initial treatment or second-line after relapse following drugs  Progressive destruction of thyroid cells  Calculated dose based on uptake value and size of gland  Hypothyroidism common  Time to normalization 4- 8 weeks  Worsen orbitopathy?  Radioiodine is treatment of choice  Concentrates within toxic nodule  Remainder of thyroid is suppressed and unaffected  Normal thyroid tissue recovers  Surgical resection is also effective  Some centres use repeat injection of ethanol solutions
  25. 25. 5/23/2014 25  During acute inflammation:  If marked local or systemic symptoms:  Prednisone 40-60 mg daily tapered over 6-8 weeks  If less symptomatic:  NSAIDs or ASA  If hypothyroid phase is prolonged and symptomatic:  Thyroxine at modest dose 50-100 ug daily 2-3 months Three additional references?

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