This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sabri, O. Articles by Buell, U. Search for Related Content PubMed PubMed Citation Articles by Sabri, O. Articles by Buell, U.

Success Rate of Radioiodine Therapy in Graves’ Disease: The Influence of Thyrostatic Medication

Departments of Nuclear Medicine and Neuropsychology (K.W.), Aachen University of Technology, Aachen, Germany

Address all correspondence and requests for reprints to: O. Sabri, Ph.D., M.D., Department of Nuclear Medicine, Aachen University of Technology, Pauwelsstrasse 30, D-52057 Aachen, Germany.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
There is controversy whether simultaneous thyrostatic medication influences the outcome of radioiodine (¹³¹I) therapy in Graves’ disease by reducing the absorbed energy dose of ¹³¹I when delivering a standard dose. We therefore sought to ascertain whether the outcome of ablative ¹³¹I therapy is in any way affected by simultaneous thyrostasis (carbimazole) by aiming for a constant absorbed dose of 200–250 Gy. We prospectively studied 207 patients with Graves’ disease (106 with and 101 without simultaneous carbimazole at the time of ¹³¹I therapy). All patients were reexamined 3, 6, and 12 months after ¹³¹I therapy. The 101 nonthyrostatic patients showed a highly significantly greater success rate (93%) than the 106 thyrostatic patients (49%). Stepwise logistic regression demonstrated that failure was related to the administration of carbimazole during ¹³¹I therapy (P < 0.00005) and the absorbed dose (P < 0.025), but was not related to free T₃, free T₄, TSH receptor antibodies, or thyroid volume. The success rate was 100% in 93 nonthyrostatic patients with absorbed doses of 200 Gy or more, but was only 12.5% (1 of 8) for absorbed doses less than 200 Gy. Correlation between success and absorbed dose was significantly higher for nonthyrostatic than for thyrostatic patients (r = 0.93 vs. r = 0.24). Sixteen patients who discontinued thyrostasis 1–3 days before ¹³¹I therapy showed 94% successes.

Simultaneous thyrostasis is the decisive factor against a successful ¹³¹I therapy even if the significantly reduced ¹³¹I uptake/half-life values under thyrostasis are compensated with a higher delivered dose to ensure a comparable absorbed dose, possibly due to the additionally effective radioprotective properties of carbimazole. Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning ¹³¹I therapy, because even in hyperthyroid nonthyrostatic patients the success rate was 100%.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
RADIOIODINE (¹³¹I) therapy has become a cornerstone in the treatment of hyperthyroidism in Graves’ disease (1). However, several reports have suggested that pretreatment with thyrostatic medication reduces the efficacy of ¹³¹I therapy in patients with Graves’ disease, although data to the contrary also exist (2, 3, 4, 5, 6). The literature seems to indicate the possibility of simultaneous thyrostatic medication reducing the absorbed dose of radioiodine (¹³¹I) when delivering a standard dose. As some studies show that simultaneous thyrostasis could reduce the uptake and effective half-life of ¹³¹I (3, 7), and others documenting the negative effects of thyrostasis on ¹³¹I therapy in Graves’ disease have suggested that an empirical increase in the delivered dose of radioiodine could bring the failure rate down to an acceptable level (4, 5, 8), we sought to ascertain whether the outcome of ablative ¹³¹I therapy is in any way affected by simultaneous thyrostasis (carbimazole, which is metabolized in vivo to methimazole) by aiming for a constant absorbed dose of 200–250 Gy. Results from a prospective randomized multicenter study have shown a strong correlation between the success of therapy (defined as the elimination of hyperthyroidism 6 months after radioiodine application) and the absorbed dose of radiation, suggesting a success rate of 80–84% for a target dose of 200–250 Gy (9, 10).

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects

We prospectively recruited 220 patients with confirmed Graves’ disease (characterized by hyperthyroidism, diffuse goiter, and serum thyroid autoantibodies). Thirteen patients failed to report to follow-up examinations, leaving 207 in the study cohort. One hundred and six patients were receiving carbimazole (10.6 ± 6.5 mg/day for 90.1 ± 46.2 days; median, 94) at the beginning of and throughout their ¹³¹I therapy, 70 of whom showed no signs of Graves’ ophthalmopathy and 36 of whom showed signs of mild ophthalmopathy (defined as proptosis <22 mm, intermittent diplopia or none, absence of optic neuropathy, and mild conjunctival and periorbital inflammation). The other 101 patients discontinued carbimazole (10.4 ± 4.9 mg/day for 90.6 ± 40.8 days; median, 88) 17.9 ± 12.2 days (median, 17) before the beginning of ¹³¹I therapy and did not receive any for the duration of the therapy, of whom 70 showed no signs of Graves’ ophthalmopathy and 31 showed signs of mild ophtalmopathy. The baseline data of the two patient groups (with and without simultaneous thyrostatic medication) are shown in Table 1.

Thyroid function was assessed by measuring serum free T₄ (fT₄), free T₃ (fT₃; Amerlex-Mab kits, Johnson & Johnson, Neckargemuend, Germany), and serum TSH (Amerlite-TSH-30, Johnson & Johnson). Normal ranges were 9.9–24.3 pmol/L for fT₄, 3.4–7.2 pmol/L for fT₃, and 0.25–4.2 mU/L for TSH. Serum TSH receptor antibodies (TRAb) were measured by RRA (TRAK assay, Brahms-Diagnostica, Berlin, Germany; normal value, 11 U/L). Hyperthyroidism was defined as an abnormally high serum fT₄ or fT₃ concentration and an undetectable serum TSH concentration; hypothyroidism was defined as an abnormally low serum fT₄ concentration and a high serum TSH concentration.

Treatment

The individual delivered dose (D) for ¹³¹I therapy was calculated by the formula (11): D (MBq) = C x target dose (Gy) x thyroid volume (mL)/maximum iodine uptake (%) x effective half-life (days), where C was the mass-dependent dose constant used as a volume-dependent variable from 26.3 for 1 mL to 22.2 for 60 mL (12). The target dose was 200–250 Gy. Maximum iodine uptake and effective half-life were determined immediately before the beginning of therapy with a radioiodine test (after oral administration of 2 MBq ¹³¹I). After application of the calculated ¹³¹I delivered dose for ¹³¹I therapy, dosimetric kinetic determinations of the actual effective half-life, the actual ¹³¹I uptake, and the actual absorbed dose were made using one or two daily measurements (12). To ensure a constant absorbed dose for both the thyrostatic (n = 106) and the nonthyrostatic (n = 101) patients, we opted for a delivered dose of 716 ± 357 and 565 ± 233 MBq, respectively (P < 0.0005; see Table 1).

Following the indications of Bartalena et al. (13, 14), patients with mild signs of ophthalmopathy were initially given 0.4–0.5 mg prednisone/kg BW, starting at the beginning of ¹³¹I therapy and continuing for 1 month, then gradually decreasing the dose and finally discontinuing it.

All patients had ultrasonography performed (for exact determination of thyroid volume) as well as fT₃, fT₄, TSH, and TRAb measurements immediately before the beginning of ¹³¹I therapy.

All patients were checked by ultrasonography as well as for fT₃, fT₄, TSH, and TRAb levels after the first 3 months of ¹³¹I therapy and again for fT₃, fT₄, and TSH levels after 6 and 12 months of treatment.

According to our ablative ¹³¹I therapy concept, success was defined as therapy-induced stable hypothyroidism after therapy (corrected with T₄ upon diagnosis); failure was defined as a persistent or recurrent hyperthyroidism after 12 months.

Statistical analysis

Baseline values in the two groups were compared using two-tailed t tests for quantitative variables and two-tailed ² tests for qualitative variables (Table 1). Significant differences between therapy success and failure in thyrostatic vs. nonthyrostatic patients were determined using ² tests. Two-tailed Fisher’s exact and ² tests were also performed to detect significant differences between therapy success and failure for an actual absorbed dose of either less than 200 Gy or 200 Gy or more for thyrostatic and nonthyrostatic patients separately. Pearson’s (point biserial) correlation coefficients between therapy success and absorbed dose were performed. Then, to detect significant differences between these correlation coefficients in the thyrostatic vs. the nonthyrostatic group, Fisher’s z' transformation was invoked (15). In addition, ² tests were performed for comparison of success vs. failure in a subgroup of 27 thyrostatic hyperthyroid vs. 23 nonthyrostatic hyperthyroid patients at the beginning of ¹³¹I therapy. Finally, in another subgroup of 12 thyrostatic patients who received low level thyrostasis for less than 10 days before beginning ¹³¹I therapy, basic data of successes vs. failures were compared with two-tailed Mann-Whitney U tests because of the small sample size. To determine whether the fact that a patient received thyrostasis during ¹³¹I therapy could be predictive of the outcome of ¹³¹I therapy, we determined the positive and negative predictive powers, which, unlike positive and negative predictive values, are not dependent upon the prevalence (giving thyrostasis or not) according to Choi (16). The dependence of therapy failure upon the predictor variables simultaneous thyrostasis, absorbed dose, thyroid function (fT₃, fT₄), thyroid volume, and TRAb values at the time of ¹³¹I therapy, was tested using stepwise logistic regression and stepwise discriminant analysis.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
There were no significant differences in the baseline characteristics between the two treatment groups, except for significant differences in delivered dose, therapeutic uptake, and effective half-life of ¹³¹I to ensure a comparable absorbed dose for both groups (Table 1).

After 3 months, 99 of the entire cohort of 207 thyrostatic and nonthyrostatic patients had become hypothyroid, 43 were hyperthyroid, and the remaining 65 presented with euthyroidism. Finally, after 12 months, 47 of these 65 euthyroid patients had become hypothyroid (success), and 18 were hyperthyroid again (failure). All patients classified as failures (n = 61; 29.5%) required a second ¹³¹I therapy (requiring carbimazole treatment due to stable hyperthyroidism until a second ¹³¹I therapy); all successes (n = 146; 70.5%) remained stable under substitution with T₄ after 12 months. Ophthalmopathy did not develop in patients without clinical evidence of eye disease before therapy. Among the patients with mild ophthalmopathy who were treated with radioiodine and prednisone, no progression of ophthalmopathy was found in any case. In therapy successes (n = 146), thyroid volume reduction after therapy was highly significantly greater than that in the 61 failures (53.7 ± 16.3% vs. 28.3 ± 17.8%; P < 0.0005). Thus, successful patients had a highly significantly lower thyroid volume after ¹³¹I therapy than failures (13.9 ± 8.4 vs. 23.9 ± 10.3 mL; P < 0.0005). TRAb values did not differ significantly before and after therapy between successes (from 63.8 ± 120.7 to 83.7 ± 151.7 U/L after therapy) and failures (from 59.9 ± 102.8 to 81.2 ± 122.9 U/L; all P > 0.2).

Table 2 shows that the nonthyrostatic group revealed a highly significantly greater success rate than the thyrostatic group.

When comparing success rates in the nonthyrostatic group between patients who reached an absorbed dose of less than 200 Gy (12.5%) and those who reached a dose of 200 Gy or more (100%), a highly significant difference was found (Table 3).

Table 5 shows a comparison of two patient subgroups who were hyperthyroid at the time of ¹³¹I therapy. Hyperthyroid patients without thyrostatic medication during ¹³¹I therapy (n = 23; fT₃, 8.4 ± 1.6; fT₄, 23.8 ± 4.9 pmol/L) showed a highly significantly greater success rate (100%) than hyperthyroid patients (n = 27; fT₃, 8.6 ± 1.6; fT₄, 23.3 ± 7.7 pmol/L) with simultaneous thyrostasis (55.6%). The two patient subgroups did not differ significantly in any of the other variables (all P > 0.32).

Even in a thyrostatic subgroup of patients (n = 12) who received a low dosage of carbimazole (9.0 ± 3.6 mg/day) starting 0–10 days (8.6 ± 2.9) before ¹³¹I therapy and continuing throughout the therapy, the success rate (n = 6; 50%) was equal to the failure rate (n = 6; 50%). Successes did not differ significantly from failures in any of the other variables (all P > 0.25).

In a nonthyrostatic subgroup of patients (n = 16) in whom thyrostasis (9.2 ± 3.8 mg carbimazole/day) was discontinued 1–3 days (1.1 ± 0.5) before starting ¹³¹I therapy, success was obtained in 15 patients (93.8%); the remaining one subject was a failure (6.2%) as a consequence of not reaching an absorbed dose of 200 Gy.

Table 6 shows positive and negative predictive powers addressing the question of whether thyrostasis during ¹³¹I therapy could predict treatment outcome. The predictive powers are the relative performance rates of therapy success or failure concerning the information of thyrostasis. Positive predictive power is 5.61, which means that the possibility of treatment failure is more than 5 times higher with simultaneous thyrostasis than without. In contrast to positive and negative predictive values, these indexes are independent of prevalence (giving thyrostasis or not), which often can only be estimated, and therefore are useful for characterizing the predictivity of screening tests (16). The higher the predictive powers, the higher the predictive accuracies regardless of the value of prevalence.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

When comparing the results of ¹³¹I therapy, one problem is that in most of the studies, not all of the factors that might influence the success rate were considered. Some studies adjusted the delivered dose only to thyroid volume and uptake and did not evaluate the actually absorbed doses (5, 8, 24, 25). Other studies, emphasizing the importance of calculated vs. standard activities, did not consider in detail the influence of simultaneous thyrostatic medication (9, 10). In this study, when evaluating all 207 patients (with and without simultaneous carbimazole), a success rate of 70.5% was found. A success rate in the range of 70–80% was also reported by several other groups (8, 9, 10, 14, 26, 27, 28). These results are somewhat lower than those obtained by surgical near-total thyroidectomy (success rate, 92–97%) according to the results of a recent prospective randomized study (28).

In our study, simultaneous thyrostasis was clearly the decisive negative factor against successful ¹³¹I therapy even after delivering a significantly higher dose of ¹³¹I, as was suggested by other groups (5, 8). Logistic regression and stepwise discriminant analysis revealed that failure was related only to the administration of thyrostasis and absorbed dose, but not to any of the other factors, even hyperthyroidism, as reported by others (2, 4). Therefore, in our study, even a subgroup of 23 nonthyrostatic patients hyperthyroid at the time of ¹³¹I therapy showed a success rate of 100%, whereas a comparable subgroup of 27 thyrostatic hyperthyroid patients showed a significantly lower success rate of only 55.6%.

Concerning thyroid volume reduction after ¹³¹I therapy, we found comparable reduction rates (25, 29). Successes showed a significantly higher volume reduction (54%) than failures (28%) despite the fact that they had comparable thyroid volumes before ¹³¹I therapy, as was shown also by Chiovato et al. (30).

Another important result of our study concerns the correlation between success and absorbed dose, as has recently been suggested (6, 9, 10). This correlation coefficient was highly significant for all of our 207 patients, but was not very strong (r = 0.44). However, there was a very strong correlation between therapy success and absorbed dose for the nonthyrostatic patient group (r = 0.93). Therefore, in the nonthyrostatic group, the success rate was 100% when an absorbed dose of 200 Gy or more was reached, which is much higher than the predicted 80% success rate (9, 10), possibly because of the missing influence of simultaneous thyrostatic medication in this group of our patient cohort. On the contrary, the thyrostatic patients showed a highly significantly lower correlation between absorbed dose and success (r = 0.24), so that the success rate was only 55.4% even when an absorbed dose of 200 Gy or more was reached. How can this be explained? This finding may imply that simultaneous thyrostatic medication not only significantly reduces ¹³¹I uptake/half-life values (which we compensated for), but the previously suggested concept of radioprotective effects of antithyroid therapy (24, 31, 32, 33) seems to be an additional important negative factor against successful ¹³¹I therapy, weakening the correlation between absorbed dose and therapy success, so that increasing the delivered doses of ¹³¹I (megabecquerels) alone, as suggested (5, 8), is not sufficient.

Some 35 yr ago, Einhorn and Säterborg (34) proposed that thioureas conferred radioresistance due to their sulfhydryl groups. As carbimazole contains no sulfhydryl group, it was suggested that this drug confers no radioresistance (34, 35). Goolden et al. (35) found equal cure rates from ¹³¹I with and without carbimazole pretreatment, but carbimazole was discontinued 3–5 days before ¹³¹I therapy. Likewise, Marcocci et al. (36) found no interference of methimazole (MMI) with ¹³¹I therapy when MMI was discontinued 5–7 days before ¹³¹I therapy. However, they also found that MMI was associated with a persistence of thyrotoxicosis when given shortly after ¹³¹I therapy. Imseis et al. (37) compared propylthiouracil (PTU) with MMI regarding their success rates with ¹³¹I therapy. They found that PTU (but not MMI) may reduce the therapeutic efficacy of subsequent ¹³¹I when they were discontinued 5–55 days before radioiodine treatment. Hancock et al. (5) found a failure rate of 29% in 17 patients discontinuing PTU 4–7 days before starting ¹³¹I therapy. Regarding comparability with our study, in all of these studies PTU as well as MMI were always discontinued before ¹³¹I therapy. Furthermore, the results were not correlated to absorbed energy doses in these studies; it is therefore not possible to distinguish definitely between the effects of reduced absorbed doses (compensated for in our study) and, additionally, radioprotective properties. However, our data do not contradict the findings of these studies, because they discontinued carbimazole before beginning ¹³¹I therapy, and we also had good results (93% success) with those 101 patients who discontinued carbimazole before ¹³¹I therapy (even with those 16 who discontinued 1–3 days before ¹³¹I), but in those 106 thyrostatic patients who did not discontinue treatment we observed an apparently additional radioprotective effect. From all of this, we speculate that if carbimazole does indeed have radioprotective properties, the time range for this effect is much shorter than that for PTU.

In conclusion, simultaneous thyrostatic medication is the decisive negative factor against successful ¹³¹I therapy, increasing the possibility of treatment failure by more than 5 times (positive predictive power, 5.6), even if significantly higher delivered doses are given to ensure absorbed doses comparable to those in nonthyrostatic patients. In nonthyrostatic patients who reach an absorbed dose of 200 Gy or more, the success rate is 100%, which is comparable to the results of surgical near-total thyroidectomy (28). Therefore, if clinically feasible, we recommend discontinuing thyrostasis at least 1 day before beginning ¹³¹I therapy, as even in hyperthyroid nonthyrostatic patients, the success rate was 100%.

	Acknowledgments

 
The authors thank A. Rodón for general and language editing.

Received October 16, 1998.

Revised December 16, 1998.

Accepted January 7, 1999.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Kabadi U, Cech R. 1994 Therapeutic 131I dose in hyperthyroidism: role of pretreatment with thionamide. Thyroidology. 6:87–92.[Medline]
2. Koroscil TM. 1995 Thionamides alter the efficacy of radioiodine treatment in patients with Graves’ disease. South Med J. 88:831–836.[Medline]
3. Kung AW, Yau CC, Cheng AC. 1995 The action of methimazole and L-thyroxine in radioiodine therapy: a prospective study on the incidence of hypothyroidism. Thyroid. 5:7–12.[Medline]
4. Franklyn JA, Daykin J, Holder R, Sheppard MC. 1995 Radioiodine therapy compared in patients with toxic nodular or Graves’ hyperthyroidism. Q J Med. 88:175–180.
5. Hancock LD, Tuttle RM, LeMar H, Bauman J, Patience T. 1997 The effect of propylthiouracil on subsequent radioactive iodine therapy in Graves’ disease. Clin Endocrinol (Oxf). 47:425–430.[CrossRef][Medline]
6. Reiners C. 1991 Radioiodine treatment of Basedow’s disease: interference and influence factors, risk estimation. Exp Clin Endocrinol. 97:275–285.[Medline]
7. Berg GEB, Michanek AMK, Holmberg ECV, Fink M. 1996 Iodine-131 treatment of hyperthyroidism: significance of effective half-life measurements. J Nucl Med. 37:228–232.[Abstract/Free Full Text]
8. Tuttle RM, Patience T, Budd S. 1995 Treatment with propylthiouracil before radioactive iodine therapy is associated with a higher treatment failure rate than therapy with radioactive iodine alone in Graves’ disease. Thyroid. 5:243–247.[Medline]
9. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H. 1997 Treatment of Graves’ hyperthyroidism with radioiodine: results of a prospective randomized study. Thyroid. 7:247–251.[Medline]
10. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H. 1995 Radioiodine therapy of Graves’ hyperthyroidism: standard vs. calculated ¹³¹iodine activity. Results from a prospective, randomized, multicentre study. Eur J Clin Invest. 25:186–193.[Medline]
11. Harbert JC. 1987 Radioiodine therapy of hyperthyroidism. In: Harbert JC, ed. Nuclear Medicine Therapy. Stuttgart: Georg Thieme Verlag; 1–36.
12. Müller B, Bares R, Büll U. 1991 Effective half-life of 131I during treatment of autonomous thyroid disease. Nuklearmedizin. 30:71–76.[Medline]
13. Bartalena L, Marcocci C, Bogazzi F, Panicucci M, Lepri A, Pinchera A. 1989 Use of corticosteroids to prevent progression of Graves’ ophthalmology after radioiodine therapy for hyperthyroidism. N Engl J Med. 321:1349–1352.[Abstract]
14. Bartalena L, Marcocci C, Bogazzi F, et al. 1998 Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med. 338:73–78.[Abstract/Free Full Text]
15. Sachs L. 1972 Z'-Tranformation. In: Sachs L, ed. Statistische Auswertungsmethoden, 3rd ed. Berlin, Heidelberg, New York: Springer; 331–335.
16. Choi BCK. 1982 Index for rating predictive accuracy of screening tests. Methods Inform Med. 21:149–153.[Medline]
17. Sridama V, McCormick M, Kaplan EL, Fauchet R, DeGroot LJ. 1984 Long-term follow-up study of compensated low-dose ¹³¹I therapy for Graves’ disease. N Engl J Med. 311:426–432.[Abstract]
18. Goolden AWG, Stewart JSW. 1986 Long-term results from graded low dose radioactive iodine therapy for thyrotoxicosis. Clin Endocrinol (Oxf). 24:217–222.[Medline]
19. Wise PH, Ahmad A, Burnet RB, Harding PE. 1975 International radioiodine ablation in Graves’ disease. Lancet. 2:1231–1233.[Medline]
20. Velkeniers B, Cytryn R, Vanhaelst, et al. 1988 Treatment of hyperthyroidism with radioiodine: adjunctive therapy with antithyroid drugs reconsidered. Lancet. 1:1127–1129.[CrossRef][Medline]
21. Reynolds LR, Kotchen TA. 1979 Antithyroid drugs and radioactive iodine. Fifteen years’ experience with Graves’ disease. Arch Intern Med. 139:651–653.[Abstract/Free Full Text]
22. Alevizaki CC, Alevizaki-Harhalaki MC, Ikkos DG. 1985 Radioiodine-131 treatment of thyrotoxicosis: dose required for and some factors affecting the early introduction of hypothyroidism. J Nucl Med. 10:450–454.[CrossRef]
23. Cunnien AJ, Hay ID, Gorman CA, Offord KP, Scanlon PW. 1982 Radioiodine-induced hypothyroidism in Graves’ disease: factors associated with the increasing incidence. J Nucl Med. 32:978–983.
24. Burch HB, Solomon BL, Wartofsky L, Burman KD. 1994 Discontinuing antithyroid therapy before ablation with radioiodine in Graves’ disease. Ann Intern Med. 121:553–559.[Abstract/Free Full Text]
25. Nygaard B, Hegedüs L, Gervil M, et al. 1995 Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves’ disease. J Intern Med. 238:491–497.[Medline]
26. DeGroot LJ, Mangklabruks A, McCormick M. 1990 Comparison of RA ¹³¹I treatment protocols for Graves’ disease. J Endocrinol Invest. 13:111–118.[Medline]
27. de Bruin TWA, Croon CDL, de Klerk JMH, van Isselt JW. 1994 Standardized radioiodine therapy in Graves’ disease: the persistent effect of thyroid weight and radioiodine uptake on outcome. J Intern Med. 236:507–513.[Medline]
28. Törring O, Tallstedt L, Wallin G, et al. 1996 Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine–a prospective randomized study. J Clin Endocrinol Metab. 81:2986–2993.[Abstract/Free Full Text]
29. Peters H, Fischer C, Bogner U, Reiners C, Schleusener H. 1996 Reduction in thyroid volume after radioiodine therapy of Graves’ hyperthyroidism: results of a prospective, randomized, multicentre study. Eur J Clin Invest. 26:59–63.[CrossRef][Medline]
30. Chiovato L, Fiore E, Vitti P, et al. 1998 Outcome of thyroid function in Graves’ patients treated with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine-induced thyroid damage. J Clin Endocrinol Metab. 83:40–46.[Abstract/Free Full Text]
31. Steinbach JJ, Donoghue GD, Goldman JK. 1979 Simultaneous treatment of toxic diffuse goitre with ¹³¹I and antithyroid drugs: a prospective study. J Nucl Med. 20:1263–1267.[Abstract/Free Full Text]
32. Connell JMC, Hilditch TE, McCruden DC, Robertson J, Alexander WD. 1984 Effect of pretreatment with carbimazole on early outcome following radio-iodine (¹³¹I) therapy. Eur J Nucl Med. 9:464–466.[CrossRef][Medline]
33. Giambarresi L, Jacobs A. 1987 Radioprotectants. In: Conklin J, Walker R, eds. Military radiobiology. Orlando: Academic Press; 265–301.
34. Einhorn J, Säterborg N-E. 1962 Antithyroid drugs in iodine 131 therapy of hyperthyroidism. Acta Radiol. 58:161–167.
35. Goolden AWG, Fraser TR. 1969 Effect of pretreatment with carbimazole in patients with thyrotoxicosis subsequently treated with radioactive iodine. Br Med J. 3:443–444.
36. Marcocci C, Gianchecchi D, Masini I, et al. 1990 A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism. J Endocrinol Invest. 13:513–520.[Medline]
37. Imseis RE, Vanmiddlesworth L, Massie JD, Bush AJ, Vanmiddlesworth NR. 1998 Pretreatment with propylthiouracil but not methimazole reduces the therapeutic efficacy of iodine-131 in hyperthyroidism. J Clin Endocrinol Metab. 83:685–687.[Abstract/Free Full Text]

This article has been cited by other articles:

				V. Markovic and D. Eterovic Thyroid Echogenicity Predicts Outcome of Radioiodine Therapy in Patients with Graves' Disease J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3547 - 3552. [Abstract] [Full Text] [PDF]

				M. A Walter, M. Briel, M. Christ-Crain, S. J Bonnema, J. Connell, D. S Cooper, H. C Bucher, J. Muller-Brand, and B. Muller Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials BMJ, March 10, 2007; 334(7592): 514 - 514. [Abstract] [Full Text] [PDF]

				S. J. Bonnema, F. N. Bennedbaek, A. Veje, J. Marving, and L. Hegedus Continuous Methimazole Therapy and Its Effect on the Cure Rate of Hyperthyroidism Using Radioactive Iodine: An Evaluation by a Randomized Trial J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2946 - 2951. [Abstract] [Full Text] [PDF]

				Radioiodine therapy for hyperthyroidism DTB, June 1, 2006; 44(6): 44 - 48. [Abstract] [Full Text] [PDF]

				B. E Jensen, S. J Bonnema, and L. Hegedus Glucocorticoids do not influence the effect of radioiodine therapy in Graves' disease Eur. J. Endocrinol., July 1, 2005; 153(1): 15 - 21. [Abstract] [Full Text] [PDF]

				D. D Streetman and U. Khanderia Diagnosis and Treatment of Graves Disease Ann. Pharmacother., July 1, 2003; 37(7): 1100 - 1109. [Abstract] [Full Text] [PDF]

				F. Bogazzi, L. Bartalena, A. Campomori, S. Brogioni, C. Traino, F. De Martino, G. Rossi, F. Lippi, A. Pinchera, and E. Martino Treatment with Lithium Prevents Serum Thyroid Hormone Increase after Thionamide Withdrawal and Radioiodine Therapy in Patients with Graves' Disease J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4490 - 4495. [Abstract] [Full Text] [PDF]

				V. A. Andrade, J. L. Gross, and A. L. Maia The Effect of Methimazole Pretreatment on the Efficacy of Radioactive Iodine Therapy in Graves' Hyperthyroidism: One-Year Follow-Up of a Prospective, Randomized Study J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3488 - 3493. [Abstract] [Full Text] [PDF]

				A. Allahabadia, J. Daykin, M. C. Sheppard, S. C. L. Gough, and J. A. Franklyn Radioiodine Treatment of Hyperthyroidism--Prognostic Factors for Outcome J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3611 - 3617. [Abstract] [Full Text] [PDF]

				H. B. Burch, B. L. Solomon, D. S. Cooper, P. Ferguson, N. Walpert, and R. Howard The Effect of Antithyroid Drug Pretreatment on Acute Changes in Thyroid Hormone Levels after 131I Ablation for Graves' Disease J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3016 - 3021. [Abstract] [Full Text] [PDF]

				A. Allahabadia, J. Daykin, R. L. Holder, M. C. Sheppard, S. C. L. Gough, and J. A. Franklyn Age and Gender Predict the Outcome of Treatment for Graves' Hyperthyroidism J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1038 - 1042. [Abstract] [Full Text]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sabri, O. Articles by Buell, U. Search for Related Content PubMed PubMed Citation Articles by Sabri, O. Articles by Buell, U.