Update In Hyperthyroidism

Transcription

1 Update In Hyperthyroidism CME Away India & Sri Lanka March 23 - April 7, 2018 Richard A. Bebb MD, ABIM, FRCPC Consultant Endocrinologist Medical Subspecialty Institute Cleveland Clinic Abu Dhabi

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3 Barriers To Change

4 Disclosure of Commercial Support This program has not received financial support, or in-kind support, from any Pharmaceutical Company. Potential for conflict(s) of interest: None to declare

5 Faculty/Presenter Disclosure Faculty: Richard Bebb Relationships with commercial interests: None to report

6 Learning Objectives: Diagnosis of hyperthyroidism Treatment of hyperthyroidism Issues specific to the Elderly Issues Specific to pregnancy

7 Sub Clinical or Mild Hyperthyroidism What are the risks of non-treatment?

8 Subclinical Hyperthyroidism Atrial Fibrillation Epidemiologic Study: Low TSH vs. A-fib Framingham database: 2007 patients 60 y.o. No A-fib at onset of 10 yr follow-up Patients grouped according to initial TSH Low (< 0.1 mu/l) Slightly low ( mu/l) Normal (> 0.4 but < 5.0 mu/l) Sawin, et al. N Engl J Med. 1994;331:

9 TSH (uu/ml) SUBCLINICAL HYPERTHYROIDISM ATRIAL FIBRILLATION Framingham > P=0.05 <0.1 P< %/10 yrs RELATIVE RISK SAWIN CT et al NEJM 331: , 1994

10 Atrial Fibrillation Incident atrial fibrillation by thyroid group TSH < 0.1 TSH euthyroid subclinical hypothyroid overt hypothyroid Years Incidence (per 1000 person-years) 126 (p=0.001) 59 (p=0.007) 31 Cappola et al, JAMA. 2006;295:

11 Subclinical Hyperthyroidism and Fracture Risk Blum M et al, JAMA. 2015;313(20):

12 Survival vs Serum TSH Age >60yrs TSH > <0.5 Parle J et al Lancet 358:861,2001

13 Case 1: 34 yr female 2 month history of anxiety, heat intolerance, palpitations, ease of sweating and 4 kg (9 lb) weight loss No FHx of thyroid disease Thyroid symmetrically enlarged, 2 x normal, stare, mild conjunctival injection, sinus rhythm TSH < 0.05 (N miu/l) {uu/ml} Free T4 44 (N pmol/l) {4.1 ng/dl}

14 Case 1: Your Next Step 1) Order a repeat TSH, T4, CBC and ESR 2) Order a thyroglobulin and a free T3 3) Order repeat free T4 & TSH & a free T3 4) Order a thyroid ultrasound 5) Order a 24 hour I 123 uptake and scan of thyroid

15 Case 1: Uptake & Scan Grave s Disease 77 % uptake at 24 hours (N 10-35%); pattern homogeneous

16 Options of Therapy 1) Anti-thyroid Drug therapy 2) Radioactive Iodine I-131 3) Thyroidectomy

17 Antithyroid Drugs The Most Common Treatment for Graves Disease in the United States Brito et al Thyroid 2016

18 ATA Guidelines: Antithyroid Drug Choice RECOMMENDATION 13 Methimazole should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm, and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgery.

19 Case 1: ATD therapy outcome Her chance of remission after 12 to 18 months of antithyroid drug therapy is: 1) 80% 2) 60% 3) 40% 4) 20% European Journal of Endocrinology, 2005, Vol 153, Issue 4, A systematic review of drug therapy for Graves hyperthyroidism P. Abraham, et al

20 Antithyroid Drug Side-Effects PTU Minor rash, GI distress 1-5% Major % Agranulocytosis MMI 1-5% (dose related) % (dose related) Drug-Induced Lupus, Arthritis, Vasculitis?<1%?<0.1% Hepatotoxicity Hepatocellular?0.1%-0.01% Avoid in young patients Usually Cholestatic (Less Common)

21 Duration of Antithyroid Drug Therapy RECOMMENDATION 22 If MMI is chosen as the primary therapy for GD, the medication should be continued for approximately months, then discontinued if the TSH and TRAb levels are normal at that time. Strong recommendation, high-quality evidence.

22 Case 1: Continued She is started on Methimazole ( carbimazole) 10 mg po BID and tapered down to 10 mg once per day over 3 months. She feels vastly improved. Free T4 normalized, TSH slightly suppressed but measurable. She presents to your clinic and advises you she is now pregnant at 7 weeks GA

23 Case 1: Your Advise 1) Stop the Methimazole / Carbimazole as she will not need it during pregnancy. 2) Increase the dose to normalize the TSH. 3) Switch her to PTU ( Propylthiouracil). 4) Advise termination of the pregnancy.

24 Aplasia Cutis secondary to Methimazole: This may be a complication of Methimazole use during pregnancy

25 Case one: continued She is converted to PTU and has a successful pregnancy. She flares post delivery and you up-titrate her medication. 11 weeks post partum you note her pulse is irregularly irregular. A 12 lead confirms atrial fibrillation. Should she be anticoagulated? Yes No Maybe Unsure

26 Case 2: 47 yr male 2 week history of heat intolerance, general malaise, night sweats, weakness, tachycardia and anterior neck discomfort Thyroid 2.5 times normal, tender. No eye signs TSH < 0.05 (N miu/l) {uu/ml} Free T4 35 (N pmol/l) {3.4 ng/dl}

27 Case 2: Additional test that might be helpful include: 1) CBC 2) Free T3 3) anti-thyroperoxidase (AMA) titer 4) ESR 5) 24 hour uptake and scan of thyroid

28 Case 2: 24 hour uptake and scan of thyroid results < 1% uptake at 24 hours ESR elevated, mild anemia Diagnosis: Subacute thyroiditis Graphic from: Am Fam Physician 2000;61: ,1054.

29 Case 2: Your Advice? 1) methimazole 20 mg po once per day 2) beta blockade for symptom control 3) prednisone mg po OD for 1 week 4) NSAID therapy

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31 Case 3: 62 yr woman 12 month history of fatigue, loose bowel motions, proximal muscle weakness and progressively poor balance 2 cm R thyroid nodule, HR 110, mild stare TSH < 0.05 (N miu/l) {uu/ml} Free T4 18 (N pmol/l) {1.7 ng/dl}

32 Case 3: Your next step? 1) order a I hour uptake and scan 2) order thyroid stimulating immunoglobulins 3) repeat the TSH & free T4 along with a free T3 4) review the patients medications

33 Case 3: Results Free T3 level twice normal, repeat Free T4 still normal Diagnosis: T3 toxicosis from an autonomous nodule

34 Case 3: Toxic Nodule 1) Advise anti-thyroid drug therapy for 18 months 2) Advise radioactive iodine therapy 3) Advise sub-total thyroidectomy

35 Radioiodine Dose: Fixed Dose or Calculated Dose? Systematic Review and Meta analysis Rooij et al. Eur J. Endocrinol 2009 Fixed or calculated: outcomes are the same.

36 Rates of Hypothyroidism After Radioiodine for Solitary Toxic Adenomas Nygaard et al. Clin Endocrinol 1999

37 Common Causes of Hyperthyroidism Grave s Disease Toxic Nodule Toxic Multi-nodular gland Inflammatory Thyroiditis Sub-acute Silent Post-Partum Drug Induced (Amiodarone, Interferon)

38 Uncommon Cause of Hyperthyroidism Thyrotoxicosis Factitia Choriocarcinoma / Molar Pregnancy Struma Ovarii TSH producing pituitary tumors Selective TSH or T4 resistant states

39 Toxic Multinodular Goiter (TMG)

40 Toxic Multinodular Goiter (TMG)

41 Severe Exophthalmia

42 Thyroid Dermopathy

43 Thyroid Acropathy Clubbing and Osteoarthropathy

44 Onycholysis

45 Issues specific to the elderly: 1)Graves disease is most common in the young. Toxic multinodular gland is most common in the very old. 2)The elderly often have minimal symptoms: Masked Hyperthyroidism Single System Hyperthyroidism Cardiac and adrenergic symptoms less due to decreased potential heart rate and common use of beta blockers 3) Atypical presentations Falls Diarrhea Unexplained Weight loss

46 Treatment of hyperthyroidism in the very elderly: Surgery is generally avoided as increased risk Radioactive I-131 favored as hyperthyroidism less tolerated and the desire to NEVER have it return is high by both patient and physician Anti-thyroid drugs may be used in the short term to render the patient euthyroid and provide a respite to recover health prior to definitive I-131

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