DISEASES OF THE THYROID Pathophysiology and management Edited by Malcolm H. Wheeler MD (Wales), FRCS (Eng) Consultant Surgeon University Hospital of Wales and Cardiff Royal Infirmary Cardiff Wales UK and John H. Lazarus MA, MD (Cantab) FRCP (Lond and Glas) Senior Lecturer and Consultant Physician University of Wales College of Medicine Cardiff Wales UK CHAPMAN & HALL London • Glasgow • Weinheim • New York • Tokyo • Melbourne • Madras Published by Chapman & Hall, 2-6 Boundary Row, London SEI 8HN, UK Chapman & Hall, 2-6 Boundary Row, London SEI 8HN, UK Blackie Academic & Professional, Wester Cleddens Road, Bishopbriggs, Glasgow G64 2NZ, UK Chapman & Hall GmbH, Pappelallee 3, 69469 Weinheim, Germany Chapman & Hall Inc., One Perm Plaza, 41st Floor, New York NY 10119, USA Chapman & Hall Japan, Thomson Publishing Japan, Hirakawacho Nemoto Building, 6F, 1-7-11 Hirakawa-cho, Chiyoda-ku, Tokyo 102, Japan Chapman & Hall Australia, Thomas Nelson Australia, 102 Dodds Street, South Melbourne, Victoria 3205, Australia Chapman & Hall India, R. Seshadri, 32 Second Main Road, CIT East, Madras 600 035, India First edition 1994 © 1994 Chapman & Hall Typeset in 10/12 Palatino by Keyset Composition, Colchester, Essex Printed in Great Britain at the University Press, Cambridge ISBN 0 412 43030 4 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the UK Copyright Designs and Patents Act, 1988, this publication may not be reproduced, stored, or transmitted, in any form or by any means, without the prior permission in writing of the publishers, or in the case of reprographic reproduction only in accordance with the terms of the licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publishers at the London address printed on this page. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. A catalogue record for this book is available from the British Library Library of Congress Catalog Card Number: 93-74436 (05? Printed on acid-free text paper, manufactured in accordance with ANSI/NISO Z39.48-1992 (Permanence of Paper). CONTENTS List of contributors ix Foreword by Sir Richard I. S. Bayliss, KCVO, MD, FRCP xiii Preface xv 1 The Evolution of Treatment of Thyroid Disease 1 (a) Medical aspects 3 Reg Hall (b) History of thyroid surgery 11 Barnard j. Harrison and Richard B. Welbourn 2 Thyroid Physiology 19 (a) Thyroid hormone production, transport and metabolism 21 Georg Hennemann, RoelofDocter and Eric P. Krenning (b) Thyroid hormone action 29 Jayne A. Franklyn (c) Thyroid cell growth 41 Allan E. Siperstein and Orlo H. Clark 3 Etiology of Benign Thyroid Disease 51 (a) Epidemiology 53 Gordon Caldwell and Michael Tunbridge (b) Genetic factors 61 David I. W. Phillips (c) Environmental aspects 73 Eduardo Gaitan (d) Immunological factors 85 Philip S. Barnett and Alan M. McGregor 4 Diagnostic Tests of Thyroid Function and Structure 105 (a) Hormone measurements 107 Rhys John and John H. Lazarus VI Contents (b) Thyroid antibodies 117 Jadwiga Furmaniak and Bernard Rees Smith (c) Thyroid imaging 131 Michael N. Maisey (d) Fine needle aspiration cytology 153 Ronald H. Nishiyama, S. Thomas Bigos and Daniel S. Oppenheim 5 Hyperthyroidism 163 (a) Clinical features 165 John H. Lazarus (b) Graves' disease 171 Anthony P. Weetman (c) The toxic solitary nodule and toxic multinodular goiter 193 Hans Bürgi (d) Other causes of hyperthyroidism 201 John H. Lazarus (e) Surgery for hyperthyroidism 207 Malcolm H. Wheeler 6 Multinodular Goiter: Diagnosis and Management 219 C. Renate Pickardt and Peter C. Scriba 7 The Solitary Thyroid Nodule 231 Malcolm H. Wheeler 8 Hypothyroidism: Etiology and Management 245 Nobuyuki Amino and Junko Tachi 9 Thyroid Disease and Pregnancy 269 John H. Lazarus 10 Etiology of Thyroid Cancer 281 (a) Molecular genetics 283 Raj V. Thakker (b) Growth factors and oncogenes 299 David Wynford-Thomas (c) Radiation-associated thyroid carcinoma 325 /. Francisco Fierro-Renoy and Leslie J. DeGroot 11 Pathology of Thyroid Cancer 343 H. Ruben Harach and Sir E. Dillwyn Williams 12 Clinical Features and Management of Thyroid Cancer (a) Differentiated thyroid carcinoma Norman W. Thompson (b) Anaplastic giant cell thyroid carcinoma Martin Bäckdahl, Bertil Hamberger, Torsten Löwhagen and Göran Lundell (c) Malignant lymphoma of the thyroid Charles /. Edmonds (d) Medullary thyroid carcinoma Jon A. van Heerden and Ian D. Hay (e) Management of metastatic thyroid cancer Martin Schlumberger (f) Prognostic factors and DNA ploidy determination in differentiated thyroid carcinoma lan D. Hay Index MULTINODULAR GOITER: DIAGNOSIS AND MANAGEMENT 6 C. Renate Pickardt and Peter C. Scriba Multinodular thyroid enlargement is a iodine deficiency and endemic goiter are symptom of different thyroid diseases with found all over the world, particularly in varying underlying pathogenetic principles mountainous areas and continental regions, (Table 6.1). From the epidemiological point where iodine prophylaxis is not used [1,3]. of view, endemic and sporadic goiters have The known data concerning the severity and to be distinguished. Goiter endemia is degree of iodine deficiency and goiter preva• assumed by definition in regions with a lence in Europe are shown in Figures 6.1, prevalence of more than 10% among the 6.2. USA, Canada and Japan and the coastal population under investigation [1]. areas of all continents are free of iodine In most endemic areas, iodine deficiency deficiency diseases. In iodine deficient re• is the main cause of goiter development. gions, iodine insufficiency is the most prob• Another cause of goiter endemia is the able cause of goiter. But neither morpholo• intake of goitrogens via the drinking water gical nor functional criteria can discriminate as in Columbia and the Himalayas specifically between endemic and sporadic (Chapter 3(c)). In other regions iodine de• goiter in an affected individual. ficiency and dietary goitrogens from veget• Sporadic goiter can be divided into cases able foodstuffs are together responsible for with a genetic background, including indi• this kind of endemic disease [2], which is viduals with congenital goiters in non- best documented for Zaire. Vegetables with endemic areas, and other cases induced by goitrogenic effect contain thioglycosides or goitrogenic drugs. Spontaneous cases may cyanogenic glycosides. In this context also arise from thyroiditis or growth stimu• cigarette smoking is thought to be a cofactor lating globulins, especially when thyroid for goitrogenesis, since it increases serum enlargement occurs suddenly. The different thiocyanate concentration. Regions with genetic defects of thyroid hormone synthesis Table 6.1 Causes of multinodular goiter Endemic Sporadic Iodine deficiency Genetic defects of thyroid hormone synthesis Dietary goitrogens Genetic defects of thyroid hormone action Environmental goitrogens Goitrogenic drugs Thyroiditis syndromes Acromegaly TSH producing pituitary adenoma Diseases of the Thyroid. Edited by Malcolm H. Wheeler and John H. Lazarus. Published in 1994 by Chapman & Hall, London. ISBN 0 412 43030 4. 220 Multinodular goiter or thyroid hormone action (T4 receptor defect) are rare causes of goiter formation, which can however result in multinodular goiter in affected families. In the minor forms of these defects there may be compensation of thyr• oid function so that the individual remains euthyroid, whereas the major forms will be detected by evidence of hypothyroidism and goiter or even cretinism early in the child• hood. Sporadic goiter induced by drugs interfer• ing with thyroid hormone synthesis or re• lease is now a rare event. This is due to the fact that indications for antithyroid drug treatment are established, dosage for hyper• thyroidism is easy to control, and side effects of substances such as lithium, carbu- tamide, fluoride and aminoglutethimide are well recognized in medical practice. Iodine induced goiters are observed main• Figure 6.1 Urinary iodine excretion (^tg/g creati• ly in limited areas in Japan, where excessive nine); updated map of the original publication intake of seaweed is thought to be responsi• [4]. (Regional values are denoted in brackets.) ble for a defect of the escape from the Wolff-Chaikoff effect. This population may develop hypothyroidism. An acute development of multinodular goiter gives rise to the suspicion of in• flammatory thyroid disease, which is painful in the case of acute thyroiditis and the subacute thyroiditis of De Quervain, or pain• less in the case of granulomatous diseases such as sarcoidosis or tuberculosis. In general, nodular transformation of the enlarged thyroid is the consequence of ear• lier diffuse thyroid enlargement under the continuing influence of the goitrogenic prin• ciple [5,6]. Therefore, patients with multi• nodular goiter usually are older than those with diffuse thyroid enlargement [5,7]. It has been shown for sporadic goiter that there is a linear relationship between age and thyr• oid volume and nodularity, respectively, with an average yearly increase of 4.5% of goiter volume, as calculated by Berghout, et al. [5,8]. During nodular transformation Figure 6.2 Goiter prevalence