The occurrence of agranulocytosis due to antithyroid drugs in a cohort of patients with Graves‘ disease treated with radioactive iodine 131I during 14 years
Authors:
Jitka Čepková; Filip Gabalec; Ioannis Svilias; Jiří Horáček
Authors‘ workplace:
IV. interní hematologická klinika LF UK a FN Hradec Králové, přednosta doc. MUDr. Pavel Žák, Ph. D.
Published in:
Vnitř Lék 2014; 60(10): 832-836
Category:
Original Contributions
Overview
Introduction:
Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves’ disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit.
Patients and methods:
We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU).
Results:
Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23–78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9–40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20–41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4–8).
Conclusion:
Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.
Key words:
agranulocytosis – carbimazole – Graves’ disease – methimazol – propylthiouracil
Sources
1. Zamrazil V. Nemoci štítné žlázy v klinické praxi. Postgrad Med J 2013; 15(7): 720–729.
2. Bahn Chair 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. Thyroid 2011; 21(6): 593–646.
3. 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): 4549–4558.
4. 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(2): 129–135.
5. Vaidya B, Williams GR, Abraham P et al. Radioiodine treatment for benign thyroid disorders: results of a nationwide survey of UK endocrinologists. Clin Endocrinol (Oxf) 2008; 68(5): 814–820.
6. Cooper DS. Antithyroid drugs. N Engl J Med 2005; 352(9): 905–917.
7. Dokupilova A, Payer J. Thyrostatic treatment and its adverse effects. Vnitř Lék 2013; 59(11): 989–995.
8. Brunová J Diagnostika a terapie poruch funkce štítné žlázy. Med pro praxi 2008; 5(9): 315–321.
9. Rajput R, Goel V. Indefinite antithyroid drug therapy in toxic Graves' disease: What are the cons. Indian J Endocrinol Metab 2013; 17(Suppl 1): S88-S92.
10. Allannic H, Fauchet R, Orgiazzi J et al. Antithyroid drugs and Graves' disease: a prospective randomized evaluation of the efficacy of treatment duration. J Clin Endocrinol Metab 1990; 70(3): 675–679.
11. Maugendre D, Gatel A, Campion L et al. Antithyroid drugs and Graves' disease – prospective randomized assessment of long-term treatment. Clin Endocrinol (Oxf) 1999; 50(1): 127–132.
12. Weetman AP. Graves' hyperthyroidism: how long should antithyroid drug therapy be continued to achieve remission? Nat Clin Pract Endocrinol Metab 2006; 2(1): 2–3.
13. Allahabadia A, Daykin J, Holder RL et al. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab 2000; 85(3): 1038–1042.
14. Nedrebo BG, Holm PI, Uhlving S et al. Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease. Eur J Endocrinol 2002; 147(5): 583–589.
15. Orunesu E, Bagnasco M, Salmaso C et al. Use of an artificial neural network to predict Graves' disease outcome within 2 years of drug withdrawal. Eur J Clin Invest 2004; 34(3): 210–217.
16. Glinoer D, de Nayer P, Bex M et al. Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study. Eur J Endocrinol 2001; 144(5): 475–483.
17. Orgiazzi J, Madec AM. Reduction of the risk of relapse after withdrawal of medical therapy for Graves' disease. Thyroid 2002; 12(10): 849–853.
18. Takasu N, Yamashiro K, Komiya I et al. Remission of Graves' hyperthyroidism predicted by smooth decreases of thyroid-stimulating antibody and thyrotropin-binding inhibitor immunoglobulin during antithyroid drug treatment. Thyroid 2000; 10(10): 891–896.
19. Abraham P, Avenell A, Park CM et al. A systematic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol 2005; 153(4): 489–498.
20. Brent GA. Clinical practice. Graves' disease. N Engl J Med 2008; 358(24): 2594–2605.
21. Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet 2012; 379(9821): 1155–1166.
22. Watanabe N, Narimatsu H, Noh JY et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease. J Clin Endocrinol Metab 2012; 97(1): E49-E53.
23. Nakamura H, Miyauchi A, Miyawaki N et al. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab 2013; 98(12): 4776–4783.
24. Takata K, Kubota S, Fukata S et al. Methimazole-induced agranulocytosis in patients with Graves' disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily. Thyroid 2009; 19(6): 559–563.
25. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 2007; 146(9): 657–665.
26. Meyer-Gessner M, Benker G, Lederbogen S et al. Antithyroid drug-induced agranulocytosis: clinical experience with ten patients treated at one institution and review of the literature. J Endocrinol Invest 1994; 17(1): 29–36.
27. Abraham P, Acharya S. Current and emerging treatment options for Graves' hyperthyroidism. Ther Clin Risk Manag 2010; 6: 29–40.
28. Ahmed K, Rao S, Simha V. Antineutrophil cytoplasmic antibody-positive vasculitis in a patient with graves disease: cross-reaction between propylthiouracil and methimazole. Endocr Pract 2010; 16(3): 449–451.
29. Bahn RS, Burch HS, Cooper DS et al. The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 2009; 19(7): 673–674.
30. Vilchez FJ, Torres I, Garcia-Valero A et al. Concomitant agranulocytosis and hepatotoxicity after treatment with carbimazole. Ann Pharmacother 2006; 40(11): 2059–2063.
31. Woeber KA. Methimazole-induced hepatotoxicity. Endocr Pract 2002; 8(3): 222–224.
32. Kaňová N. Tyreostatika stále aktuální. DMEV 2007; 10(1): 37–42.
33. Tajiri J, Noguchi S, Murakami T et al. Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. Arch Intern Med 1990; 150(3): 621–624.
34. Dai WX, Zhang JD, Zhan SW et al. Retrospective analysis of 18 cases of antithyroid drug (ATD)-induced agranulocytosis. Endocr J 2002; 49(1): 29–33.
35. Pearce SH. Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK. Clin Endocrinol (Oxf) 2004; 61(5): 589–594.
36. Fukata S, Kuma K, Sugawara M. Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study. Thyroid 1999; 9(1): 29–31.
37. Andres E, Kurtz JE, Perrin AE et al. Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis. QJM 2001; 94(8): 423–428.
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Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
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