Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome

Summary 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 ± 376.4 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 Gyvs. 285.2 ±82.1 Gy, ρ <0.005), but with no significant differences regarding age, thyroid volume, function or TRAb (all ρ >0.2). Of the 14 failures, η = 8 reached an absorbed dose <200 Gy and η = 1 a dose <250 Gy, although 5 of the failures reached an absorbed dose of >250 Gy. Stepwise logistic regression revealed only absorbed energy dose as a variable significantly influencing therapy success (p <0.005), but no influence of initial thyroid volume, function, TRAb value, age (all ρ >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, ρ = 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.

Download Full-text

Radioiodine therapy of Graves’ disease — a dosimetric comparison of different strategies concerning antithyroid drugs

Nuklearmedizin ◽

10.1055/s-0038-1625922 ◽

2001 ◽

Vol 40 (04) ◽

pp. 111-115 ◽

Cited By ~ 7

Author(s):

V. Urbannek ◽

E. Voth ◽

D. Moka ◽

H. Schicha

Keyword(s):

Half Life ◽

Radioiodine Therapy ◽

Thyroid Volume ◽

Absorbed Dose ◽

The Body ◽

Antithyroid Drugs ◽

Graves Disease ◽

Thyroid Metabolism ◽

Group A ◽

Group B

SummaryAim: Premedication with antithyroid drugs (ATD) compared to patients not pretreated with ATD causes a higher failure rate of radioiodine therapy (RITh) or demands higher therapeutical dosage of radioiodine (Rl). For clinical reasons and because of accelerated iodine metabolism in hyperthyreosis a compensated thyroid metabolism is desirable. Aim of this study was to investigate the influence of ATD on the biokinetics of Rl in case of Graves’ disease in order to improve RITh of patients pretreated with ATD. Methods: 385 consecutive patients who underwent RITh because of Graves’ disease for the first time were included: Group A (n = 74): RITh under continuous medication with ATD; Group B (ç = 111): Application of Rl under continuous medication with ATD, in case of insufficient Rl-uptake or shortened effective Rl-half-life ATD were stopped 1-5 days after RITh; Group C (n = 200): ATD were stopped 2 days prior to RITh in all patients. We examined the influence of ATD on Rl-uptake and effective Rl-half-life as well as the absorbed dose achieved on the thyroid in dependence of thyroid volume and applied Rl-dosage [TEQ - therapy efficiency quotient, (2)]. Results: In the Rl-pretest (all patients under ATD) the Rl-uptake was comparable in all three groups. During RITh Rl-uptake, effective Rl-half-life and therefore the TEQ were significantly higher in Group C as compared to Groups A and B (ñ <0,001, respectively). In Group B the medication with ATD was stopped in 61 of 111 cases 1-5 days after RITh. In this subgroup the effective Rl-half-life increased from 4,4 ± 1,7 d to 5,1 ± 1,6 d after stopping of ATD (ñ = 0,001). Conclusion: Stopping of ATD 2 days prior to RITh leads to an increased efficiency of about 50% compared to RITh carried out under ATD and therefore to a clear reduction of radiation exposure to the rest of the body with equal absorbed doses of the thyroid. Stopping of ATD shortly after RITh increases efficiency in case of short effective Rl-half-life, but it is inferior to stopping ATD 2 days prior to RITh.

Download Full-text

Guideline for radioiodine therapy for benign thyroid diseases (version 3)

Nuklearmedizin ◽

10.1055/s-0038-1623919 ◽

2004 ◽

Vol 43 (06) ◽

pp. 217-220 ◽

Cited By ~ 8

Author(s):

J. Dressler ◽

F. Grünwald ◽

B. Leisner ◽

E. Moser ◽

Chr. Reiners ◽

...

Keyword(s):

Radioiodine Therapy ◽

Thyroid Volume ◽

Thyroid Diseases ◽

Antithyroid Drugs ◽

Graves Disease ◽

Co Morbidity ◽

History Of ◽

Individual Decisions ◽

Prophylactic Use ◽

Benign Thyroid

SummaryThe version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves’ disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves’ disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient’s preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients’ preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.

Download Full-text

RADIOIODINE TREATMENT OF GRAVES’ DISEASE – DOSE/RESPONSE ANALYSIS

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2014.39 ◽

2014 ◽

Vol 57 (2) ◽

pp. 49-55 ◽

Cited By ~ 2

Author(s):

Jitka Čepková ◽

Jiří Horáček ◽

Jaroslav Vižďa ◽

Jiří Doležal

Keyword(s):

Clinical Outcome ◽

Dose Range ◽

Antithyroid Drug ◽

Thyroid Volume ◽

Complete Response ◽

Response Analysis ◽

Graves Disease ◽

Success Rates ◽

Cure Rate ◽

Significant Difference

The clinical outcome of 153 Graves’ disease patients treated with a wide dose range of radioactive iodine-131 (RAI) was analyzed retrospectively. Six to nine months after the first dose of RAI 60 patients (39%) were hypothyroid (or rather thyroxine-substituted) and 26 (17%) were euthyroid, while 67 patients (44%) did not respond properly: in 32 (21%) their antithyroid drug (ATD) dose could be reduced but not withdrawn (partial response) and 35 (23%) remained hyperthyroid or the same dose of ATD was necessary (no response). The outcome did not correspond significantly to the administered activity of RAI (medians 259, 259, 222, and 259 MBq for hypothyroid, euthyroid, partial, and no response subgroups, respectively), or the activity retained in the gland at 24 h (medians 127, 105, 143, and 152 MBq). The effect was, however, clearly, and in a stepwise pattern, dependent on initial thyroid volume (17, 26, 33 and 35 ml, P < 0.001) or activity per gram tissue retained at 24 h (6.02, 4.95, 4.75, and 4.44 MBq/g, P = 0.002). Also, higher residual level of thyrotoxicosis at the time of RAI treatment was connected with worse outcome. The dose-dependency of outcome was further analyzed. When our sample was divided into tertiles, according to the adjusted dose, the same modest success rates (47%) were seen in the lower and middle tertiles. However, doses higher than 5.88 MBq/g (the upper tertile) resulted in success rate of 75%. Finer division into decils has shown a threshold-like increase in cure rate between the 7th and the 8th decil. In the first 7 decils (doses ≤ 6 MBq/g) the complete response rate was 45 to 50%, in the 8th decil (6.0 to 7.8~MBq/g) it rose to 80% and was not further increased with increasing dose. Direct comparison of higher (> 6 MBq/g, cure rate 80%) and lower (≤ 6 MBq/g, cure rate 46%) doses gave highly significant difference (P < 0.001). With our dosing range we found a dose-dependent clinical outcome that suggests an optimum delivered dose near 6.5 MBq/g, resulting in successful treatment of ca 80% patients.

Download Full-text

Thyroid Echogenicity Predicts Outcome of Radioiodine Therapy in Patients with Graves’ Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0879 ◽

2007 ◽

Vol 92 (9) ◽

pp. 3547-3552 ◽

Cited By ~ 25

Author(s):

Vinko Marković ◽

Davor Eterović

Keyword(s):

Radioiodine Therapy ◽

Independent Predictor ◽

Prospective Trial ◽

Absorbed Dose ◽

University Hospital ◽

Graves Disease ◽

Hospital Outpatient Clinic ◽

Increased Radioresistance ◽

Hypothyroid Patients

Abstract Context: Despite accounting for variations in gland size and iodine kinetics, the success of radioiodine therapy in patients with Graves’ disease remains moderately common and unpredictable. Objectives: We hypothesized that hypoechogenic glands, with large, densely packed cells, are more radiosensitive than normoechogenic glands, in which much radiation is wasted on more abundant colloid. We evaluated this hypothesis in a cohort of patients with Graves’ disease. Design: This was a prospective trial of patients recruited during 4 yr and followed up 1 yr after radioiodine therapy. Setting: This trial was held in a university hospital-outpatient clinic. Patients: A total of 177 consecutive patients with first presentation of Graves’ disease (28 males), 23–76 yr old, who relapsed after antithyroid therapy were included in the study. Intervention: The patients were assigned to an ablative target-absorbed dose of 200 Gy (n = 78) or randomly to 100 or 120 Gy of nonablative dose (n = 99). Main Outcome Measures: The measures were incidences of hyperthyroidism, euthyroidism, and hypothyroidism at 12-month follow-up. Results: At follow-up there were 25 hyperthyroid, 44 euthyroid, and 108 hypothyroid patients. Compared with 96 patients with a hypoechogenic gland, in 81 patients with a normoechogenic gland, there were more hyperthyroid (22 vs. 7%) and euthyroid (41 vs. 11%), but less hypothyroid outcomes (37 vs. 81%; P < 0.0001). The other independent predictor of increased radioresistance was the large gland volume. Conclusion: In patients with Graves’ disease, normoechogenic and large glands are associated with increased radioresistance.

Download Full-text

Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves' disease

Journal of Internal Medicine ◽

10.1111/j.1365-2796.1995.tb01230.x ◽

1995 ◽

Vol 238 (6) ◽

pp. 491-497 ◽

Cited By ~ 34

Author(s):

Birte Nygaard ◽

L. HEGEDÜS ◽

M. GERVIL ◽

H. HJALGRIM ◽

B. M. HANSEN ◽

...

Keyword(s):

Radioiodine Therapy ◽

Thyroid Volume ◽

Graves Disease

Download Full-text

Predictors of the efficacy of radioiodine therapy of Graves’ disease in children and adolescents

Problems of Endocrinology ◽

10.14341/probl12390 ◽

2020 ◽

Vol 66 (4) ◽

pp. 68-76

Author(s):

Pavel O. Rumyantsev ◽

Vladimir A. Saenko ◽

Dali S. Dzeytova ◽

Alexey A. Trukhin ◽

Marina S. Sheremeta ◽

...

Keyword(s):

Logistic Regression ◽

Statistical Analysis ◽

Children And Adolescents ◽

Radioiodine Therapy ◽

Antithyroid Drug ◽

Thyroid Volume ◽

Tsh Receptor ◽

Rank Test ◽

Graves Disease ◽

Fisher Exact Test

RATIONALE: Insufficient world–wide clinical experience in radioiodine therapy (RIT) for Graves’ disease (GD) in children and adolescents, and limited knowledge of the predictors of RIT efficacy.AIMS: Analysis and identification of the most significant predictors of the efficacy of RIT in children and adolescents with Graves’ disease.MATERIALS AND METHODS: A total of 55 patients (48 females and 7 males) aged from 8 to 18 years receiving primary RIT for GD were enrolled. RIT planning was based on the dosimetric method. Analyzed parameters included gender, age, ultrasound thyroid volume before and 6 months after treatment, the presence of endocrine ophthalmopathy, duration of antithyroid drug (ATD) therapy, relapse of thyrotoxicosis after ATD dose reduction, blood fT3, fT4 and TSH levels initially and at 1, 3, 6 months after treatment, TSH receptor Ab initially and at 3 and 6 months after treatment, thyroid 99mTc–pertechnetate uptake at 10–20 minutes (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g) and therapeutic 131I activity (MBq). Fisher exact test, non–parametric Mann–Whitney test, Wilcoxon signed–rank test, logistic regression modelling, ROC–analysis, proportional hazard model (the Cox regression), the Kaplan–Meier method and log–rank test were used for statistical analysis as appropriate.RESULTS: Six months after RIT, hypothyroidism was achieved in 45 (81.8%), euthyroid state – in 2 (3.6%), and in 8 (14.6%) patients thyrotoxicosis persisted. On univariate statistical analysis, the smaller thyroid volume, higher fT4 and lower TSH receptor Ab levels, lower 99mTc–pertechnetate uptake and higher specific 131I uptake were associated with hypothyroidism. On multivariate logistic regression analysis, the older patient’s age (p=0.011), smaller thyroid volume (p=0.003) and higher fT4 (p=0.024) were independent predictors of RIT efficacy. Thyroid volume was also the only variable associated with achievement of hypothyroidism in time after RIT (p=0.011).CONCLUSION: The efficacy of dosimetry–based RIT in children and adolescents with GD 6 months after treatment was 81.2%. Older patients’ age, smaller thyroid volume and higher fT4 level were independent predictors of therapy success. Smaller thyroid volume was also a predictor of the favorable time–related outcome. Statistical models obtained in this work may be used to prospectively estimate the chance of efficient RIT for GD in pediatric patients.

Download Full-text

Anticlastogenic Effect of Ginkgo Biloba Extract in Graves’ Disease Patients Receiving Radioiodine Therapy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0597 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4286-4289 ◽

Cited By ~ 29

Author(s):

A. Dardano ◽

M. Ballardin ◽

M. Ferdeghini ◽

E. Lazzeri ◽

C. Traino ◽

...

Keyword(s):

Placebo Group ◽

Clinical Outcome ◽

Ginkgo Biloba ◽

Radioiodine Therapy ◽

Statistical Significance ◽

Ginkgo Biloba Extract ◽

131I Therapy ◽

Graves Disease ◽

Egb 761 ◽

Significant Difference

Abstract Background: Chromosomal damage, as assessed by clastogenic factors (CFs) and micronuclei (MN) appearance, after radioiodine therapy of Graves’ disease has been reported. Objective and Methods: Our objective was to evaluate the effect of Ginkgo biloba extract (EGb 761) supplementation on the time course (up to 120 d) of CFs and MN appearance in lymphocytes from patients with Graves’ disease after iodine-131 (131I) therapy. Patients were randomly assigned to EGb 761 or placebo, in a blinded manner. Results: In the placebo group, MN increased early (P < 0.001) after 131I, peaking at the 21st day (P = 0.0003) and declining thereafter. In EGb 761-treated patients, MN increased early (P < 0.05), while returning toward baseline value thereafter. Therefore, mean MN increment was significantly higher in the placebo group as compared with EGb 761-treated patients (P < 0.01). Moreover, an early (P < 0.0001) and sustained (up to 35 d; P < 0.001) MN increase induced by CFs was observed in the placebo group. Conversely, in EGb 761-treated patients, MN increase induced by CFs never reached the statistical significance; therefore, the mean of the MN increments was significantly lower than in placebo (P < 0.05). A significant positive correlation between MN maximum increment and the bone marrow dose was observed in the placebo group only (P = 0.03). No significant difference was observed in clinical outcome between the two groups. Conclusions: EGb 761 supplementation neutralized genotoxic damage induced by radioiodine treatment, without affecting the clinical outcome. Although 131I therapy is generally safe, our data suggest that Gingko biloba extracts may prevent genetic effects of radioiodine therapy for hyperthyroid Graves’ disease.

Download Full-text

Results of a risk adapted and functional radioiodine therapy in Graves’ disease

Nuklearmedizin ◽

10.1055/s-0038-1625320 ◽

2005 ◽

Vol 44 (06) ◽

pp. 238-242 ◽

Cited By ~ 8

Author(s):

V. Neumann ◽

U. Staub ◽

P. Groth ◽

H. Künstner ◽

C. Schümichen ◽

...

Keyword(s):

Radioiodine Therapy ◽

Thyroid Volume ◽

Therapeutic Failure ◽

Graves Disease ◽

Clinical Parameters ◽

Target Dose ◽

Therapeutic Success ◽

Thyroid Metabolism ◽

First Time

SummaryAim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves’ disease could be optimized using a risk adopted dose concept. Patients, method: 351 patients with Graves’ disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on average 8 ± 2,4 (4-17,2) months. TSH ≥0,27 μIU/mL confirmed as a measure of the success. Results: With improved pretherapeutic dosimetry and a mean target dose of 178 ± 31 Gy (n=72) therapeutic success occurred in 66,7%, in 51,4% euthyreosis was restalled and in 15,3% of patients hypothyroidism was seen (TSH >4,20 μIU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 ± 29 Gy (n=279) results were moderately impaired (63,8%, 40,1% and 23,7%). With increasing target dose therapeutic failure increased, as unsufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. Conclusion: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer.

Download Full-text

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.4.5588 ◽

1999 ◽

Vol 84 (4) ◽

pp. 1229-1233 ◽

Cited By ~ 1

Author(s):

Osama Sabri ◽

Michael Zimny ◽

Gernot Schulz ◽

Mathias Schreckenberger ◽

Patrick Reinartz ◽

...

Keyword(s):

Success Rate ◽

Standard Dose ◽

Thyroid Volume ◽

Absorbed Dose ◽

131I Therapy ◽

Stepwise Logistic Regression ◽

Graves Disease ◽

Free T4 ◽

Absorbed Doses ◽

Receptor Antibodies

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%.

Download Full-text