Background: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and/or metastases to produce thyroid hormone. Case: A 68-year-old male, with weight loss and palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for follicular variant of papillary thyroid carcinoma, and total thyroidectomy was performed. One week after thyroidectomy the patient was admitted with severe hyperthyroidism. TRAB was >40 IU/mL (normal <0.7 IU/mL). High-dose antithyroid drug treatment was followed by high-dose radioactive iodine-131 (RAI) and local radiotherapy covering the right shoulder. Antithyroid drug treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. Summary and Conclusions: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested that TRAB stimulated the highly differentiated extrathyroidal metastatic thyroid tissue to produce excessive amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the course of thyroid cancer.

Keywords:
Thyroid cancer, Thyrotropin receptor antibodies, Metastases, Post-thyroidectomy thyroid storm, Case report
1.
Smith TJ, Hegedus L: Graves’ Disease. N Engl J Med 2016; 375:1552–1565.
2.
Carle A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, Laurberg P: Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study. Eur J Endocrinol 2011; 164:801–809.
3.
Brix TH, Kyvik KO, Christensen K, Hegedus L: Evidence for a major role of heredity in Graves’ disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab 2001; 86:930–934.
4.
Brix TH, Hansen PS, Kyvik KO, Hegedus L: Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med 2000; 160:661–666.
5.
Wiersinga WM: Smoking and thyroid. Clin Endocrinol (Oxf) 2013; 79:145–151.
6.
Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G: High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves’ disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J Intern Med 1991; 229:415–420.
7.
Brandt F, Thvilum M, Almind D, Christensen K, Green A, Hegedus L, Brix TH: Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study. PLoS One 2013; 8:e66711.
8.
Chen YK, Lin CL, Chang YJ, Cheng FT, Peng CL, Sung FC, Cheng YH, Kao CH: Cancer risk in patients with Graves’ disease: a nationwide cohort study. Thyroid 2013; 23:879–884.
9.
Shu X, Ji J, Li X, Sundquist J, Sundquist K, Hemminki K: Cancer risk in patients hospitalised for Graves’ disease: a population-based cohort study in Sweden. Br J Cancer 2010; 102:1397–1399.
10.
Brandt F, Almind D, Christensen K, Green A, Brix TH, Hegedus L: Excess mortality in hyperthyroidism: the influence of preexisting comorbidity and genetic confounding: a Danish nationwide register-based cohort study of twins and singletons. J Clin Endocrinol Metab 2012; 97:4123–4129.
11.
Yano Y, Shibuya H, Kitagawa W, Nagahama M, Sugino K, Ito K, Ito K: Recent outcome of Graves’ disease patients with papillary thyroid cancer. Eur J Endocrinol 2007; 157:325–329.
12.
Hales IB, McElduff A, Crummer P, Clifton-Bligh P, Delbridge L, Hoschl R, Poole A, Reeve TS, Wilmshurst E, Wiseman J: Does Graves’ disease or thyrotoxicosis affect the prognosis of thyroid cancer. J Clin Endocrinol Metab 1992; 75:886–889.
13.
Belfiore A, Garofalo MR, Giuffrida D, Runello F, Filetti S, Fiumara A, Ippolito O, Vigneri R: Increased aggressiveness of thyroid cancer in patients with Graves’ disease. J Clin Endocrinol Metab 1990; 70:830–835.
14.
Pellegriti G, Mannarino C, Russo M, Terranova R, Marturano I, Vigneri R, Belfiore A: Increased mortality in patients with differentiated thyroid cancer associated with Graves’ disease. J Clin Endocrinol Metab 2013; 98:1014–1021.
15.
Akamizu T, Satoh T, Isozaki O, Suzuki A, Wakino S, Iburi T, Tsuboi K, Monden T, Kouki T, Otani H, Teramukai S, Uehara R, Nakamura Y, Nagai M, Mori M; Japan Thyroid Association: Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid 2012; 22:661–679.
16.
Al-Omari AA, Haddad FH, Khushman HM, Malkawi OM: Graves disease and papillary thyroid cancer. An association that can be missed. Saudi Med J 2005; 26:1280–1282.
17.
Suzuki K, Nakagawa O, Aizawa Y: A case of pulmonary metastatic thyroid cancer complicated with Graves’ disease. Endocr J 2001; 48:175–179.
18.
Hegedus L, Bonnema SJ, Bennedbaek FN: Management of simple nodular goiter: current status and future perspectives. Endocr Rev 2003; 24:102–132.
19.
Bonnema SJ, Hegedus L: Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr Rev 2012; 33:920–980.
20.
Bennedbaek FN, Gram J, Hegedus L: The transition of subacute thyroiditis to Graves’ disease as evidenced by diagnostic imaging. Thyroid 1996; 6:457–459.
21.
Yu HM, Park SH, Lee JM, Park KS: Graves’ disease that developed shortly after surgery for thyroid cancer. Endocrinol Metab (Seoul) 2013; 28:226–230.
22.
Kikuchi S, Perrier ND, Ituarte P, Siperstein AE, Duh QY, Clark OH: Latency period of thyroid neoplasia after radiation exposure. Ann Surg 2004; 239:536–543.
© 2017 European Thyroid Association
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.