Abstract
Background
The management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists for Graves’ disease (GD) include any of the following modalities: 131I therapy, antithyroid medication, or thyroidectomy. No in-depth analysis has been performed comparing the treatment options, even though a single treatment option seems to be universally accepted.
Methods
A systematic review of the literature was performed to examine contemporary literature between 2001 and 2011 evaluating the management options of GD. We compiled retrospective and prospective studies analyzing surgery and radioactive iodine. Outcomes of interest included postoperative hypothyroidism, euthyroidism, and persistent or recurrent hyperthyroidism without supplementation. Success was defined as postoperative euthyroidism or hypothyroidism. Failure was defined as persistent or recurrent hyperthyroidism.
Results
Of the 14,245 patients, 4,546 underwent surgery [3,158 patients had subtotal thyroidectomy (STT) and 1,388 had total thyroidectomy (TT)] and 9,699 had radioactive iodine. The radioactive iodine group consisted of 2,383 patients receiving 1–10 mCi, 1,558 patients receiving 11–15 mCi, 516 patients receiving >15 mCi, and 5,242 patients receiving an unspecified amount. Surgery was found to be 3.44 times more likely to be successful than radioactive iodine (p < 0.001). STT and TT were found to be 2.33 and 94.45 times more likely to be successful than radioactive iodine (p < 0.001), respectively.
Conclusions
On the basis of the outcomes analyzed, surgery appears to be the most successful in the management of GD, with TT being the preferred surgical option.
Similar content being viewed by others
References
Prabhakar BS, Bahn RS, Smith TJ. Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev. 2003;24:802–35.
Hegedüs L. Treatment of Graves’ hyperthyroidism: evidence-based and emerging modalities. Endocrinol Metab Clin North Am. 2009;38:355–71.
Brent GA. Clinical practice. Graves’ disease. N Engl J Med. 2008;358:2594–605.
Abraham-Nordling M, Wallin G, Träisk F, et al. Thyroid-associated ophthalmopathy; quality of life follow-up of patients randomized to treatment with antithyroid drugs or radioiodine. Eur J Endocrinol. 2010;163:651–7.
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.
Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993;22:263–77.
Brandt F, Green A, Hegedüs L, Brix TH. A critical review and meta-analysis of the association between overt hyperthyroidism and mortality. Eur J Endocrinol. 2011;165:491–7.
Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17:456–520.
Vitti P, Rago T, Chiovato L, et al. Clinical features of patients with Graves’ disease undergoing remission after antithyroid drug treatment. Thyroid. 1997;7:369–75.
Benker G, Reinwein D, Kahaly G, et al. Is there a methimazole dose effect on remission rate in Graves’ disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs. Clin Endocrinol (Oxf). 1998;49:451–7.
Hedley AJ, Young RE, Jones SJ, Alexander WD, Bewsher PD. Antithyroid drugs in the treatment of hyperthyroidism of Graves’ disease: long-term follow-up of 434 patients. Scottish Automated Follow-up Register Group. Clin Endocrinol (Oxf). 1989;31:209–18.
Wartofsky L, Glinoer D, Solomon B, et al. Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan, and the United States. Thyroid. 1991;1:129–35.
Haejin I, Pearce EN, Wong AK, Burgess JF, McAneny DB, Rosen JE. Treatment options for Graves disease: a cost-effectiveness analysis. J Am Coll Surg. 2009;209:170–9.e171–2.
Abós D, Ruiz P, Prats E, et al. [Treatment of Graves-Basedow’s disease with 131I. Assessment of a “modulated fixed activity” protocol]. Rev Esp Med Nucl. 2007;26:3–10.
Adamali HI, Gibney J, O’Shea D, Casey M, McKenna TJ. The occurrence of hypothyroidism following radioactive iodine treatment of toxic nodular goiter is related to the TSH level. Ir J Med Sci. 2007;176:199–203.
Agarwal A, Mishra SK. Role of surgery in the management of Graves’ disease. J Indian Med Assoc. 2001;99:252, 254–6.
Ahmad AM, Ahmad M, Young ET. Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis. Eur J Endocrinol. 2002;146:767–75.
Al-Kaabi JM, Hussein SS, Bukheit CS, Woodhouse NJ, Elshafie OT, Bererhi H. Radioactive iodine in the treatment of Graves’ disease. Saudi Med J. 2002;23:1049–53.
Alexander EK, Larsen PR. High dose of (131)I therapy for the treatment of hyperthyroidism caused by Graves’ disease. J Clin Endocrinol Metab. 2002;87:1073–7.
Alfadda A, Malabu UH, El-Desouki MI, et al. Treatment of Graves’ hyperthyroidism—prognostic factors for outcome. Saudi Med J. 2007;28:225–30.
Allahabadia A, Daykin J, Sheppard MC, Gough SC, Franklyn JA. Radioiodine treatment of hyperthyroidism—prognostic factors for outcome. J Clin Endocrinol Metab. 2001;86:3611–7.
Bal CS, Kumar A, Pandey RM. A randomized controlled trial to evaluate the adjuvant effect of lithium on radioiodine treatment of hyperthyroidism. Thyroid. 2002;12:399–405.
Bogazzi F, Giovannetti C, Fessehatsion R, et al. Impact of lithium on efficacy of radioactive iodine therapy for Graves’ disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal. J Clin Endocrinol Metab. 2010;95:201–8.
Chen DY, Schneider PF, Zhang XS, He ZM, Jing J, Chen TH. Striving for euthyroidism in radioiodine therapy of Graves’ disease: a 12-year prospective, randomized, open-label blinded end point study. Thyroid. 2011;21:647–54.
Chi SY, Hsei KC, Sheen-Chen SM, Chou FF. A prospective randomized comparison of bilateral subtotal thyroidectomy versus unilateral total and contralateral subtotal thyroidectomy for graves’ disease. World J Surg. 2005;29:160–3.
Collier A, Ghosh S, Hair M, Malik I, McGarvie J. Comparison of two fixed activities of radioiodine therapy (370 vs. 555 MBq) in patients with Graves’ disease. Hormones (Athens). 2009;8:273–8.
Digonnet A, Willemse E, Dekeyser C, et al. Near total thyroidectomy is an optimal treatment for Graves’ disease. Eur Arch Otorhinolaryngol. 2010;267:955–60.
Dunkelmann S, Kuenstner H, Nabavi E, Rohde B, Groth P, Schuemichen C. Change in the intrathyroidal kinetics of radioiodine under continued and discontinued antithyroid medication in Graves’ disease. Eur J Nucl Med Mol Imaging. 2007;34:228–36.
Dunkelmann S, Kunstner H, Nabavi E, Eberlein U, Groth P, Schumichen C. Lithium as an adjunct to radioiodine therapy in Graves’ disease for prolonging the intrathyroidal effective half-life of radioiodine. Useful or not? Nuklearmedizin. 2006;45:213–8.
Efremidou EI, Papageorgiou MS, Liratzopoulos N, Manolas KJ. The efficacy and safety of total thyroidectomy in the management of benign thyroid disease: a review of 932 cases. Can J Surg. 2009;52:39–44.
El Refaei SM, Shawkat W. Long-term carbimazole intake does not affect success rate of radioactive 131Iodine in treatment of Graves’ hyperthyroidism. Nucl Med Commun. 2008;29:642–8.
Eschmann SM, Thelen MH, Dittmann H, Bares R. Influence of short-term interruption of antithyroid drugs on the outcome of radioiodine therapy of Graves’ disease: results of a prospective study. Exp Clin Endocrinol Diabetes. 2006;114:222–6.
Gaujoux S, Leenhardt L, Tresallet C, et al. Extensive thyroidectomy in Graves’ disease. J Am Coll Surg. 2006;202:868–73.
Grodski S, Stalberg P, Robinson BG, Delbridge LW. Surgery versus radioiodine therapy as definitive management for graves’ disease: the role of patient preference. Thyroid. 2007;17:157–60.
Grosso M, Traino A, Boni G, et al. Comparison of different thyroid committed doses in radioiodine therapy for Graves’ hyperthyroidism. Cancer Biother Radiopharm. 2005;20:218–23.
Hao ST, Reasner CA 2nd, Becker RA. Use of cold iodine in patients with Graves’ disease: observations from a clinical practice. Endocr Pract. 2001;7:438–42.
Hautzel H, Pisar E, Yazdan-Doust N, Schott M, Beu M, Muller HW. Qualitative and quantitative impact of protective glucocorticoid therapy on the effective 131I half-life in radioiodine therapy for Graves disease. J Nucl Med. 2010;51:1917–22.
Hernandez-Jimenez S, Pachon-Burgos A, Aguilar-Salinas CA, et al. Radioiodine treatment in autoimmune hyperthyroidism: analysis of outcomes in relation to dosage. Arch Med Res. 2007;38:185–9.
Howarth D, Epstein M, Lan L, Tan P, Booker J. Determination of the optimal minimum radioiodine dose in patients with Graves’ disease: a clinical outcome study. Eur J Nucl Med. 2001;28:1489–95.
Jensen BE, Bonnema SJ, Hegedus L. Glucocorticoids do not influence the effect of radioiodine therapy in Graves’ disease. Eur J Endocrinol. 2005;153:15–21.
Kobe C, Eschner W, Sudbrock F, et al. Graves’ disease and radioiodine therapy. Is success of ablation dependent on the achieved dose above 200 Gy? Nuklearmedizin. 2008;47:13–7.
Körber C, Schneider P, Körber-Hafner N, Hänscheid H, Reiners C. Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves’ disease and toxic nodular goitre? Eur J Nucl Med. 2001;28:1360–4.
Koyuncu A, Aydin C, Topcu O, Gokce ON, Elagoz S, Dokmetas HS. Could total thyroidectomy become the standard treatment for Graves’ disease? Surg Today. 2010;40:22–5.
Ku CF, Lo CY, Chan WF, Kung AW, Lam KS. Total thyroidectomy replaces subtotal thyroidectomy as the preferred surgical treatment for Graves’ disease. ANZ J Surg. 2005;75:528–31.
Lal G, Ituarte P, Kebebew E, Siperstein A, Duh QY, Clark OH. Should total thyroidectomy become the preferred procedure for surgical management of Graves’ disease? Thyroid. 2005;15:569–74.
Leow MK, Loh KC, Zhu M, Chan SP, Sundram FX. Iodine-131 therapy for hyperthyroidism prescribed by endocrinologist—our preliminary experience. Exp Clin Endocrinol Diabetes. 2009;117:616–21.
Leslie WD, Ward L, Salamon EA, Ludwig S, Rowe RC, Cowden EA. A randomized comparison of radioiodine doses in Graves’ hyperthyroidism. J Clin Endocrinol Metab. 2003;88:978–83.
Liu J, Bargren A, Schaefer S, Chen H, Sippel RS. Total thyroidectomy: a safe and effective treatment for Graves’ disease. J Surg Res. 2011;168:1–4.
Markovic V, Eterovic D. Thyroid echogenicity predicts outcome of radioiodine therapy in patients with Graves’ disease. J Clin Endocrinol Metab. 2007;92:3547–52.
Metso S, Jaatinen P, Huhtala H, Luukkaala T, Oksala H, Salmi J. Long-term follow-up study of radioiodine treatment of hyperthyroidism. Clin Endocrinol (Oxf). 2004;61:641–8.
Moreno P, Gomez JM, Gomez N, et al. Subtotal thyroidectomy: a reliable method to achieve euthyroidism in Graves’ disease. Prognostic factors. World J Surg. 2006;30:1950–6.
Muller PE, Bein B, Robens E, Bein HS, Spelsberg F. Thyroid surgery according to Enderlen-Hotz or Dunhill: a comparison of two surgical methods for the treatment of Graves’ disease. Int Surg. 2001;86:112–6.
Nonchev BI, Terzieva DD, Dimov RS, Mateva NG, Tsvetkova TZ, Dimitrakov DY. Early hypothyroidism after subtotal thyroidectomy in patients with Graves’ disease—the role of the preoperative conservative treatment and hormonal status. Folia Med (Plovdiv). 2005;47:40–5.
Okosieme OE, Chan D, Price SA, Lazarus JH, Premawardhana LD. The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism. Clin Endocrinol (Oxf). 2010;72:122–7.
Palestini N, Grivon M, Durando R, Freddi M, Odasso C, Robecchi A. Thyroidectomy for Graves’ hyperthyroidism. Retrospective study of patients’ appreciation. Ann Ital Chir. 2007;78:405–12.
Panareo S, Rossi R, Fabbri S, et al. A practical method for the estimation of therapeutic activity in the treatment of Graves’ hyperthyroidism. Q J Nucl Med Mol Imaging. 2011;55:576–85.
Pirnat E, Zaletel K, Gaberscek S, Fidler V, Hojker S. Early changes of thyroid hormone concentrations after (131)I therapy in Graves’ patients pretreated or not with methimazole. Nuklearmedizin. 2004;43:129–34.
Razvi S, Basu A, McIntyre EA, Wahid ST, Bartholomew PH, Weaver JU. Low failure rate of fixed administered activity of 400 MBq 131I with pre-treatment with carbimazole for thyrotoxicosis: the Gateshead Protocol. Nucl Med Commun. 2004;25:675–82.
Regalbuto C, Marturano I, Condorelli A, Latina A, Pezzino V. Radiometabolic treatment of hyperthyroidism with a calculated dose of 131-iodine: results of one-year follow-up. J Endocrinol Invest. 2009;32:134–8.
Reinhardt MJ, Brink I, Joe AY, et al. Radioiodine therapy in Graves’ disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome. Eur J Nucl Med Mol Imaging. 2002;29:1118–24.
Robert J, Mariethoz S, Pache JC, et al. Short- and long-term results of total vs. subtotal thyroidectomies in the surgical treatment of Graves’ disease. Swiss Surg. 2001;7:20–4.
Sankar R, Sekhri T, Sripathy G, Walia RP, Jain SK. Radioactive iodine therapy in Graves’ hyperthyroidism: a prospective study from a tertiary referral centre in north India. J Assoc Physicians India. 2005;53:603–6.
Santos RB, Romaldini JH, Ward LS. Propylthiouracil reduces the effectiveness of radioiodine treatment in hyperthyroid patients with Graves’ disease. Thyroid. 2004;14:525–30.
Sanyal D, Mukhhopadhyay P, Pandit K, et al. Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects with Graves’ disease. J Indian Med Assoc. 2008;106:360–1, 372.
Schiavo M, Bagnara MC, Calamia I, et al. A study of the efficacy of radioiodine therapy with individualized dosimetry in Graves’ disease: need to retarget the radiation committed dose to the thyroid. J Endocrinol Invest. 2011;34:201–5.
Schneider P, Korber C, Korber-Hafner N, Hanscheid H, Reiners C. Does an individual estimation of halflife improve the results of radioiodine therapy of Graves’ disease? Nuklearmedizin. 2002;41:240–4.
Shi GM, Xu Q, Zhu CY, Yang YL. Influence of propylthiouracil and methimazole pre-treatment on the outcome of iodine-131 therapy in hyperthyroid patients with Graves’ disease. J Int Med Res. 2009;37:576–82.
Sugino K, Ito K, Nagahama M, Kitagawa W, Shibuya H. Surgical management of Graves’ disease—10-year prospective trial at a single institution. Endocr J. 2008;55:161–7.
Takamura Y, Nakano K, Uruno T, et al. Changes in serum TSH receptor antibody (TRAb) values in patients with Graves’ disease after total or subtotal thyroidectomy. Endocr J. 2003;50:595–601.
Vijayakumar V, Ali S, Nishino T, Nusynowitz M. What influences early hypothyroidism after radioiodine treatment for Graves’ hyperthyroidism? Clin Nucl Med. 2006;31:688–9.
Walter MA, Christ-Crain M, Schindler C, Muller-Brand J, Muller B. Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison. Eur J Nucl Med Mol Imaging. 2006;33:730–7.
Wang RF, Tan J, Zhang GZ, Meng ZW, Zheng W. A comparative study of influential factors correlating with early and late hypothyroidism after (131)I therapy for Graves’ disease. Chin Med J (Engl). 2010;123:1528–2.
Werga-Kjellman P, Zedenius J, Tallstedt L, Traisk F, Lundell G, Wallin G. Surgical treatment of hyperthyroidism: a ten-year experience. Thyroid. 2001;11:187–92.
Wilhelm SM, McHenry CR. Total thyroidectomy is superior to subtotal thyroidectomy for management of Graves’ disease in the United States. World J Surg. 2010;34:1261–4.
Zantut-Wittmann DE, Ramos CD, Santos AO, et al. High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves’ disease. Nucl Med Commun. 2005;26:957–63.
Dionigi G, Dionigi R. Standardization of intraoperative neuromonitoring of recurrent laryngeal nerve in thyroid operation: to the editor. World J Surg. 2010;34:2794–5.
Palit TK, Miller CC, Miltenburg DM. The efficacy of thyroidectomy for Graves’ disease: a meta-analysis. J Surg Res. 2000;90:161–5.
Hall P, Berg G, Bjelkengren G, et al. Cancer mortality after iodine-131 therapy for hyperthyroidism. Int J Cancer. 1992;50:886–90.
Stålberg P, Svensson A, Hessman O, Akerström G, Hellman P. Surgical treatment of Graves’ disease: evidence-based approach. World J Surg. 2008;32:1269–77.
Chiapponi C, Stocker U, Mussack T, Gallwas J, Hallfeldt K, Ladurner R. The surgical treatment of Graves’ disease in children and adolescents. World J Surg. 2011;35:2428–31.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Genovese, B.M., Noureldine, S.I., Gleeson, E.M. et al. What Is the Best Definitive Treatment for Graves’ Disease? A Systematic Review of the Existing Literature. Ann Surg Oncol 20, 660–667 (2013). https://doi.org/10.1245/s10434-012-2606-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-012-2606-x