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Annals of Surgical Oncology

, Volume 21, Issue 13, pp 4174–4180 | Cite as

Failure of Radioactive Iodine in the Treatment of Hyperthyroidism

  • David F. Schneider
  • Philip E. Sonderman
  • Michaela F. Jones
  • Kristin A. Ojomo
  • Herbert Chen
  • Juan C. Jaume
  • Diane F. Elson
  • Scott B. Perlman
  • Rebecca S. Sippel
Endocrine Tumors

Abstract

Background

Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patiedlxnts require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism.

Methods

We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis.

Results

Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02–1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22–5.33; p = 0.01) were associated with failure.

Conclusions

Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

Keywords

Hyperthyroidism Total Thyroidectomy Radioactive Iodine High Heart Rate Methimazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

This study was supported by NIH T32 CA009614-23.

Disclosures

David F. Schneider, Philip E. Sonderman, Michaela F. Jones, Kristin A. Ojomo, Herbert Chen, Juan C. Jaume, Diane F. Elson, Scott B. Perlman, and Rebecca S. Sippel have no conflicts of interest to disclose.

Supplementary material

10434_2014_3858_MOESM1_ESM.tiff (1.5 mb)
Percentage failure by RAI dose and initial T3 levels. Data are expressed as the percentage of patients within the indicated RAI dose (a) or initial T3 level (b) who failed RAI. RAI radioactive iodine. Supplementary material 1 (TIFF 1521 kb)

References

  1. 1.
    Astrup A, Buemann B, Christensen NJ, Madsen J, Gluud C, Bennett P, et al. The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women. J Clin Endocrinol Metab. 1992;74(2):279–86.PubMedGoogle Scholar
  2. 2.
    Wilber JF. Thyrotropin releasing hormone: secretion and actions. Annu Rev Med. 1973;24:353–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Siegel E, Tobias CA. Actions of thyroid hormones on cultured human cells. Nature. 1966;212(5068):1318–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Ross DS. Radioiodine therapy for hyperthyroidism. N Engl J Med. 2011;364(6):542–50.PubMedCrossRefGoogle Scholar
  5. 5.
    Schussler-Fiorenza CM, Bruns CM, Chen H. The surgical management of Graves’ disease. J Surg Res. 2006;133(2):207–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Wartofsky L, Glinoer D, Solomon B, Nagataki S, Lagasse R, Nagayama Y, et al. Differences and similarities in the diagnosis and treatment of Graves’ disease in Europe, Japan, and the United States. Thyroid. 1991;1(2):129–35.PubMedCrossRefGoogle Scholar
  7. 7.
    Burch HB, Burman KD, Cooper DS. A 2011 survey of clinical practice patterns in the management of Graves’ disease. J Clin Endocrinol Metab. 2012;97(12):4549–58.PubMedCrossRefGoogle Scholar
  8. 8.
    Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21(6):593–646.PubMedCrossRefGoogle Scholar
  9. 9.
    Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8(6):457–69.PubMedGoogle Scholar
  10. 10.
    Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, et al. Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine: a prospective, randomized study. Thyroid Study Group. J Clin Endocrinol Metab. 1996;81(8):2986–93.PubMedGoogle Scholar
  11. 11.
    Porterfield JR Jr, Thompson GB, Farley DR, Grant CS, Richards ML. Evidence-based management of toxic multinodular goiter (Plummer’s Disease). World J Surg. 2008;32(7):1278–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Hegedus L. Treatment of Graves’ hyperthyroidism: evidence-based and emerging modalities. Endocrinol Metab Clin North Am. 2009;38(2):355–71.PubMedCrossRefGoogle Scholar
  13. 13.
    Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves’ patients. J Clin Endocrinol Metab. 2004;89(9):4229–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Wong KP, Lang BH. Graves’ ophthalmopathy as an indication increased the risk of hypoparathyroidism after bilateral thyroidectomy. World J Surg. 2011;35(10):2212–18.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Rudberg C, Johansson H, Akerstrom G, Tuvemo T, Karlsson FA. Graves’ disease in children and adolescents. Late results of surgical treatment. Eur J Endocrinol. 1996;134(6):710–15.PubMedCrossRefGoogle Scholar
  16. 16.
    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(3):1073–77.PubMedGoogle Scholar
  17. 17.
    Chen DY, Jing J, Schneider PF, Chen TH. Comparison of the long-term efficacy of low dose 131I versus antithyroid drugs in the treatment of hyperthyroidism. Nucl Med Commun. 2009;30(2):160–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Sztal-Mazer S, Nakatani VY, Bortolini LG, Boguszewski CL, Graf H, de Carvalho GA. Evidence for higher success rates and successful treatment earlier in Graves’ disease with higher radioactive iodine doses. Thyroid. 2012;22(10):991–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Kendall-Taylor P, Keir MJ, Ross WM. Ablative radioiodine therapy for hyperthyroidism: long term follow up study. Br Med J (Clin Res Ed). 1984;289(6441):361–3.CrossRefGoogle Scholar
  20. 20.
    Sundaresh V, Brito JP, Wang Z, Prokop LJ, Stan MN, Murad MH, et al. Comparative effectiveness of therapies for Graves’ hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013;98(9):3671–77.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    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):1–4.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Welch KC, McHenry CR. Total thyroidectomy: is morbidity higher for Graves’ disease than nontoxic goiter? J Surg Res. 2011;170(1):96–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Yip J, Lang BH, Lo CY. Changing trend in surgical indication and management for Graves’ disease. Am J Surg. 2012;203(2):162–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SC, Franklyn JA. Age and gender predict the outcome of treatment for Graves’ hyperthyroidism. J Clin Endocrinol Metab. 2000;85(3):1038–42.PubMedGoogle Scholar
  25. 25.
    Hernandez-Jimenez S, Pachon-Burgos A, Aguilar-Salinas CA, Andrade V, Reynoso R, Rios A, et al. Radioiodine treatment in autoimmune hyperthyroidism: analysis of outcomes in relation to dosage. Arch Med Res. 2007;38(2):185–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Grosso M, Traino A, Boni G, Banti E, Della-Porta M, Manca G, et al. Comparison of different thyroid committed doses in radioiodine therapy for Graves’ hyperthyroidism. Cancer Biother Radiopharm. 2005;20(2):218–23.PubMedCrossRefGoogle Scholar
  27. 27.
    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(5):641–48.PubMedCrossRefGoogle Scholar
  28. 28.
    Caruso DR, Mazzaferri EL. Intervention in Graves’ disease. Choosing among imperfect but effective treatment options. Postgrad Med. 1992;92(8):117–24, 128–19, 133–34.Google Scholar
  29. 29.
    de los Santos ET, Mazzaferri EL. Thyrotoxicosis. Results and risks of current therapy. Postgrad Med. 1990;87(5):277–8, 281–6, 291–4.Google Scholar
  30. 30.
    Stan MN, Bahn RS. Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid. 2010;20(7):777–83.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, et al. Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group. JAMA. 1998;280(4):347–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Metso S, Auvinen A, Huhtala H, Salmi J, Oksala H, Jaatinen P. Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer. 2007;109(10):1972–79.PubMedCrossRefGoogle Scholar
  33. 33.
    Smith JJ, Chen X, Schneider DF, Nookala R, Broome JT, Sippel RS, Chen H, Solorzano CC. Toxic nodular goiter and cancer: a compelling case for thyroidectomy. Ann Surg Oncol. 2013;20(4):1336–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ. 2007;334(7592):514.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Imseis RE, Vanmiddlesworth L, Massie JD, Bush AJ, Vanmiddlesworth NR. Pretreatment with propylthiouracil but not methimazole reduces the therapeutic efficacy of iodine-131 in hyperthyroidism. J Clin Endocrinol Metab. 1998;83(2):685–7.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • David F. Schneider
    • 1
  • Philip E. Sonderman
    • 1
  • Michaela F. Jones
    • 1
  • Kristin A. Ojomo
    • 1
  • Herbert Chen
    • 1
  • Juan C. Jaume
    • 2
  • Diane F. Elson
    • 2
  • Scott B. Perlman
    • 3
  • Rebecca S. Sippel
    • 1
  1. 1.Section of Endocrine Surgery, Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Division of Endocrinology, Diabetes, and Metabolism, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  3. 3.Section of Nuclear Medicine, Department of RadiologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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