The occurrence of agranulocytosis due to antithyroid drugs in a cohort of patients with Graves‘ disease treated with radioactive iodine ¹³¹I during 14 years

Česká verzia

Authors: Jitka Čepková; Filip Gabalec; Ioannis Svilias; Jiří Horáček
Authors place of work: IV. interní hematologická klinika LF UK a FN Hradec Králové, přednosta doc. MUDr. Pavel Žák, Ph. D.
Published in the journal: Vnitř Lék 2014; 60(10): 832-836
Category: Original Contributions

Summary

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

Zdroje

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.