Canadian Endocrine Review Course 2014
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1 Canadian Endocrine Review Course 2014 Amiodarone & Thyrotoxicosis Iodine, A Catch 22 Ally P.H. Prebtani Associate Professor of Medicine Internal Medicine, Endocrinology & Metabolism McMaster University Canada
2 Canadian Endocrine Review Course Ally Prebtani has no potential for conflict of interest with this presentation
3 Faculty/Presenter Disclosure Faculty: Dr Ally Prebtani Rela3onships with commercial interests:* Grants/Research Support: NONE Speakers Bureau/Honoraria: NONE Consul3ng Fees: NONE Other: NONE
4 Disclosure of Commercial Support This program has received financial support from Eli Lilly/ Boehringer Ingelheim, Novo Nordisk, Pfizer, Sanofi, Astra/BMS, Merck, NovarHs, Serono/EMD, Janssen in the form of an Unrestricted EducaHonal Grant This program has not received in- kind support from any commercial organizahon
5 Amiodarone & Iodine Class III Anti-arrhythmic Similar structure to thyroid hormone 37% Iodine by weight 75mg Iodine in 200mg tablet Releases 10% free Iodine = 7.5mg od Normal intake = mg od Lipophilic Fat, Heart, Skeletal Muscle, Thyroid t 1/2 = days
6 Prevalence
7 Amiodarone Physiology Inhibits intrapituitary & peripheral 5 DI Dec T4 --> T3 conversion Inhibits Peripheral T4 & T3 uptake Desethylamiodarone (DES) Metabolite T3 antagonist Iodine Inhibits 5 DI Transient (10-14d) Wolf-Chaikoff effect
8 Effects on TFT s Euthyroid Patients Test Up to 3 mos > 3 mos T4 Inc Inc T3 Dec Dec TSH Transient inc N < 20 rt3 Inc Inc
9 Pathophysiology Amiodarone Direct Cytotoxic effect (Type II) Inflammation --> thyroiditis Autoimmune (Type I) Iodine Very controversial Jod-Basedow effect (Type I) Increased hormone production Cytotoxic (Type II)?? Autoimmune (Type I)
10 Risk Factors Hx Thyroid Dysfunction Iodine deficiency Family History Autoimmune Goitre/MNG Thyroid Antibodies
11 Clinical Apathetic/Subtle Older, Beta-blocked, decreased T3 Cardiac Arrhythmias, Ischemia, CHF Neuro Weakness, Mental status, Depression Weight loss, Fatigue Thyroid Gland Goitre, Nodule(s), Bruit Orbitopathy, Skin
12 DDx Type I Increased thyroid hormone production Jod-Basedow effect due to excess Iodine Pre-existing thyroid dysfunction Type II Grave s & MNG Preformed T4/T3 release due to destruction Normal thyroid gland More abrupt, 1-3 month duration, Self-limited Mixed Hypothyroid phase
13 Clues to DDx 80% Dx Tc-99m Scan ok on Tx Duration Thyroid Bx?? JCEM, Daniels GH, 86(1), 3-8, 2001
14 Other Clues Spontaneous remissions common Monitor for Hypothyroidism Repeat TFT testing in 6 weeks
15 Management Can be difficult No large RCT s Sick patients High Intrathyroidal Iodine content < Effective Antithyroid Drugs (ATD) Long t 1/2 Can t usually d/c Amiodarone Therapy depends on Type I vs Type II Often can t differentiate Mixed
16 Amiodarone Discontinuation Effects long-lasting, several months Potential Paradoxical danger esp CVS Beta-blockade T3 DES as T3 antagonist Loss of Iodine effect on release of T4 Continue ATD & taper 24hr urine Iodide normal Over 3-6 months
17 Antithyroid Drugs Type I, Mixed, Uncertain & Sick Higher doses needed since ++ Intrathyroidal Iodine Methimazole (MMZ) 30-60mg daily Propylthiouracil(PTU) mg qid
18 Glucocorticoids Type II, Mixed, Uncertain & Sick Prednisone 40-60mg X 7-14 days Taper over 2-3 months Esp if ++ CVS Sx Rapid effect in days Normal in 1 week if Type II Anti-inflammatory decreased thyroglobulin proteolysis Dec T4 --> T3
19 Potassium Perchlorate (KClO4) Type I, Mixed, Uncertain & Sick po 250 mg q6h (use < 1 month) Discharges Iodine from thyroid gland Decreases Iodide uptake Increases ATD efficacy Concerns Aplastic anemia Nephrotic syndrome Not big issue if < 1 month & monitoring
20 Lithium Type I, Not 1st line Tx Similar mechanism as Iodine Dickstein G et al. Am J Med 1997 May;102(5): n = 21, not randomized 5 Amio withdrawal & 7 PTU mg 11 week recovery 9 PTU 300 mg & Li daily (sicker) 4 week recovery w/o ADR (p < 0.01)
21 I-131 Type I Definitive Tx If RAIU >> 1%, Repeat prn? rtsh stimulation Once stable Radiation thyroiditis Eye disease Contact precautions Hypothyroidism
22 Thyroidectomy Definitive Tx Refractory to medical Tx Thyroid storm Cardiac instability When immediate euthyroid state required Low morbidity & mortality despite thinking Possible under local anesthesia depends on surgeon & centre
23 Plasmapheresis Severe Transient effect Variable success Case reports only
24 Other Iopanoic Acid Type I & II? If Prednisone contraindicated Pre-op Decreases T4/T3 release T4 --> T3 Vascularity Cholestyramine Binds thyroid hormone Dialysis
25 Suggested Approach Thyrotoxicosis (confirmed on repeat testing in 6 weeks) Hx & Physical d/c Amiodarone if possible Beta-Blockade TPO, Tg Ab, TRAB RAIU CFDS/Ultrasound IL-6? Type I Type II Uncertain Mixed/Sick ATD KClO4 prn? Lithium Glucocorticoids? Iopanoic Acid ATD Glucorticoids prn KClO4 prn? Lithium ATD Glucocorticoids KClO4 prn? Lithium Iopanoic Acid Cholestyramine I-131 Thyroidectomy I-131 Thyroidectomy I-131 Thyroidectomy Plasmapheresis Dialysis
26 Bottom Line Not uncommon but limited EBM Presentation Apathetic, CV Sx Types Clues I & II, Mixed Not always easy to DDx Hx & PE Labs Imaging Tx Response Management Depends on Type Often empirical Ongoing Monitoring important
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