Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to (131)I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of (131)I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of (131)I therapy in patients with nontoxic nodular goiter.

Radioiodine Therapy in Benign Thyroid Diseases: Effects, Side Effects, and Factors Affecting Therapeutic Outcome

Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or 3 days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T3, fT4, TSH) followed up after 3, 6 and 12 months. Primary endpoint was outcome 12 months after radioiodine therapy. A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves’ disease, n=90). The overall success rate was 71.5%. Patients without and 3 days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0–16) and 1 (0–10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0–30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3 days’ discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT4, T3 and TSH. Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3 days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidism.

/pdf/outcome-of-radioiodine-therapy-without-on-or-3-days-off-1o0dd8mpkl.pdf

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison.

Background High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates.



Materials and methods  We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 ± 14 years) suffering from toxic adenoma, multinodular goitre or Graves’ disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment.



Results  Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes (P = 0·002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves’ disease.



Conclusion  In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated.

Radioiodine therapy in hyperthyroidism: inverse correlation of pretherapeutic iodine uptake level and post-therapeutic outcome

Several therapeutic options are available for the treatment of Graves' disease (GD), including long-term antithyroid drug medication (ATD), near-total resection (NTR) and radioiodine therapy (RIT). These treatments are used with different frequencies depending on geographical location, size of the goitre, age of the patient and experience of the physician. It should be noted that RIT is still being applied more frequently in the United States than in Europe. Despite the fact that RIT was introduced as long ago as 1941, several questions are still the subject of debate: Should a fixed dose or a calculated dose be used. If the dose is calculated, how many Grays (Gy) should be delivered to the thyroid? What is the goal of RIT in GD? Which factors, including ATD, influence the outcome of RIT? Is RIT appropriate in GD with Graves' ophthalmopathy (GO)? Although not all these questions have been answered yet, conclusions can be derived regarding a general strategy for use of RIT in GD. As with surgery, the goal of RIT in GD is euthyroidism with or without L-thyroxine medication. There is a clear advantage of dose calculation over use of a fixed dose because the only factor influencing the outcome is the dose delivered to a certain thyroid volume. To minimise recurrent hyperthyroidism, an ablative approach using a delivered dose of 250 Gy is widely accepted. Beside pretherapeutic T3 levels, thyroid volume and 24-h thyroid uptake, ATD may influence the outcome of RIT. Today it is accepted by most thyroidologists that, if ATD medication is necessary in overt hyperthyroidism, it should be withdrawn at least 2 days before RIT. In patients with GD and GO, RIT may worsen GO. If RIT is performed in GO it should be done under a 3-month steroid medication regimen. In conclusion, RIT can be considered an appropriate and cost-effective therapy in GD, although the decision regarding treatment should be taken on an individual basis, paying due respect to the course and severity of disease, the presence of GO and, last but not least, the wishes of the patient.

Strategies of radioiodine therapy for Graves' disease.

ObjectiveThe first dose of radioiodine (131I) does not always cure hyperthyroidism in patients with Graves’ disease (GD). Our aim was to evaluate the factors influencing the success of 131I therapy.Patients and methodsWe reviewed the medical records of 724 patients who were first diagnosed with GD b

Factors influencing the success of radioiodine therapy in patients with Graves' disease.

Aim of this study was a characterization of radioiodine therapy (RIT) failures in Graves' disease without simultaneous Carbimazole. Method: 226 patients with a confirmed diagnosis of Graves' disease received 686.8 ± 3/6.4 MBq of iodine-131 orally for thyroid ablation. Target dose was 250 Gy. All patients were followed up for 6 months. Therapy failures were compared with successes regarding possible influencing variables initial thyroid volume, thyroid function, immune activity (TRAb), 1-131 uptake, effective half-life, absorbed energy dose, age and gender. Results: 212 of 226 patients (93.8%) were treated successfully, 14 (6.2%) showed a hyperthyroidism relapse within 6 months which required a second radioiodine therapy. A success rate of 92.5% (62/67) could also be achieved with 67 patients who were hyperthyroid at the time of RIT. Compared to the therapy successes, the 14 failures achieved significantly lower absorbed doses (223.8 ± 76.6 Gy vs. 285.2 ±82.1 Gy, p 0.2). Of the 14 failures, n = 8 reached an absorbed dose 250 Gy. Stepwise logistic regression revealed only absorbed energy dose as a variable significantly influencing therapy success (p 0.2) or gender (p = 0.13). Two-tailed Fisher's exact test showed no significant influence of gender on success rates (failures/successes: male 1/36, female 13/176, p = 0.48). Conclusions: Except for the absorbed energy dose, no other significant variable influencing the outcome of radioiodine therapy in Graves' disease without simultaneous Carbimazole could be found. It should be noted, though, that 5 therapy failures (2.2%) reached an absorbed energy dose of >250 Gy.

Characterization of radioiodine therapy failures in Graves' disease

Charakterisierung von Therapieversagern bei der Radioiodtherapie des Morbus Basedow ohne simultane Thyreostase

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Characterization of radioiodine therapy failures in Graves' disease

Charakterisierung von Therapieversagern bei der Radioiodtherapie des Morbus Basedow ohne simultane Thyreostase