Radioiodine Treatment of Graves Hyperthyroidism
Jiri Horacek and
Jayne A. Franklyn
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital Edgbaston, Birmingham B15 2TH, United Kingdom
Address correspondence to: Jayne A. Franklyn, M.D., Ph.D., University of Birmingham, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, United Kingdom. E-mail: j.a.franklyn{at}bham.ac.uk.
To the editor:
In a recent issue of JCEM, Leslie et al. (1) describe their randomized comparison of two fixed doses and two volume and uptake-adjusted doses of iodine-131 in the treatment of Graves hyperthyroidism. They found no difference in clinical outcome and conclude that dose adjustment does not confer any advantage over a fixed dose.
Although the randomized approach and careful and long-term follow-up are welcome, there may be important limitations to the study. The sample size was relatively small so that their negative results may reflect lack of power (and consequently a type 2 error). The authors appropriately considered persistent or recurrent hyperthyroidism as treatment failure, reporting the rates of failure below (Table 1
):
These data suggest the absence of important differences between these treatment groups, however, 95% confidence intervals for these failure rates were wide (Table 2
):
It is possible, therefore, that real and clinically significant differences in outcome exist between groups. Sample sizes required to detect (or rule out) such differences are considerably larger than those in the present study. For example, to detect at 5% significance level, a difference of 10%, e.g. a fall in treatment failure rate from 25 to 15%, with 80% power would require 270 patients in each group and for 90% power 354 patients (2). Furthermore, the present study used relatively low doses of 131-I: low fixed 235 MBq, high fixed 350 MBq, low adjusted 2.96 MBq/g, and high adjusted 4.44 MBq/g, in contrast to other recently published series (3) and in contrast to the practice in our United Kingdom center (fixed dose of 375 or 600 MBq) (4). Also, from the recent randomized trials cited in the study (5, 6), the message would be to use higher doses. Jarlov et al. (5) used fixed doses of 185, 370, and 555 MBq for gland volumes below 30, 30 to 60, and above 60 ml, respectively, and an adjusted dose 3.7 MBq/g with a reported failure rate of 35 to 41%. As the mean thyroid gland volume in Leslies study (1) was relatively high at over 60 ml, many patients treated with fixed doses would fall into Jarlovs 555-MBq group. Peters et al. (6) compared a fixed dose of 555 MBq with a lower adjusted dose calculated to deliver 100 Gy (roughly 4.7 MBq/g) and whereas they had somewhat better results with the fixed dose (failure rate, 29% vs. 42%), from the dose-response relationship they recommend individualization aimed at about 200 Gy (roughly 9.5 MBq/g). Also, preliminary data from our Czech center and dose-response analysis suggest a decrease in failure rate with doses over 6.2 MBq/g (7).
We therefore consider the randomized study of Leslie et al. (1) as an important advance in the investigation of optimal radioiodine dosing in Graves disease but not as the final step. We suggest that a randomized study comparing a fixed dose of 555 to 600 MBq with an adjusted dose of approximately 6.5 MBq/g and sample sizes of up to 300 patients in each treatment arm is desirable.
Footnotes
Present address for J.H.: Department of Medicine, Faculty of Medicine in Hradec Kralove, Charles University in Prague, CZ-50005 Hradec Kralove, Czech Republic.
A response to this letter was invited, but the authors of the original article chose not to provide one.
Received July 8, 2003.
References
- Leslie WD, Ward L, Salamon EA, Ludwig S, Rowe RC, Cowden EA 2003 A randomized comparison of radioiodine doses in Graves hyperthyroidism. J Clin Endocrinol Metab 88:978983[Abstract/Free Full Text]
- Armitage P, Berry G, Matthews JNS 2002 Statistical methods in medical research. 4th ed. Oxford, UK: Blackwell Science Ltd.; 758
- Alexander EK, Larsen PR 2002 High dose of (131)I therapy for the treatment of hyperthyroidism caused by Graves disease. J Clin Endocrinol Metab 87:10731077[Abstract/Free Full Text]
- Alahabadia A, Daykin J, Sheppard MC, Gough SCL, Franklyn JA 2001 Radioiodine treatment of hyperthyroidismprognostic factors for outcome. J Clin Endocrinol Metab 86:36113617[Abstract/Free Full Text]
- Jarlov AE, Hegedus L, Kristensen LO, Nygaard B, Hansen JM 1995 Is calculation of the dose in radioiodine therapy worthwhile? Clin Endocrinol (Oxf) 43:325329[Medline]
- Peters H, Fischer C, Bogner U, Reiners C, Schleusener H 1995 Radioiodine therapy of Graves hyperthyroidism: standard vs. calculated 131-iodine activity. Results from a prospective, randomized, multicentre study. Eur J Clin Invest 25:186193[Medline]
- Horacek J, Maly J, Spalkova I, Vizda J, Radioiodine treatment of Graves diseasedose/response analysis. Proc Sixth European Congress of Endocrinology, Lyon, France, 2003 (Abstract P 0224)