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Background: The actions of thyrotropin-binding inhibitory immunoglobulins (TBIIs) against thyrotropin receptors in thyroid follicular cells have been studied as important etiological factors in Graves' disease (GD). The purpose of this study was to investigate changes in the TBII levels of patients undergoing total thyroidectomy (TTx) or radioactive iodine (RAI) therapy for GD refractory to antithyroid drugs (ATDs). Methods: We enrolled patients who underwent TTx or RAI for GD with previous ATD use between January 2011 and December 2017 at the Samsung Medical Center in Seoul, Korea. Thorough retrospective reviews of medical records were performed in 130 patients. Results: Patients with goiter, ophthalmopathy, high levels of TBIIs, and high doses of ATDs received TTx. Elderly patients with arrhythmia received RAI. We observed that TBII levels continued to decrease after TTx. On the contrary, TBIIs initially increased for 138 days (estimated median time) and then decreased slowly after RAI. A faster decline in TBII levels was observed in the TTx group than in the RAI group ( p  < 0.001). The estimated median time for TBIIs to decrease below 4.5 IU (3 × upper normal limit, which is known to be a risk factor for fetal hyperthyroidism) was 318 days in the TTx group and 659 days in the RAI group, respectively. In the RAI group, high levels of TBII (>4.5 IU/L) were present in 70 (82%) at 6 months, 57 (67%) at 1 year, and 3 (3%) at 2 years. In the TTx group, rapid decreases in TBII levels were observed in younger patients and those with lower baseline TBII levels. In the RAI group, smaller thyroid volume was correlated with more rapid decrease in TBII levels. Conclusions: The changes in TBII levels following TTx or RAI were different in patients with refractory GD. When deciding on TTx or RAI, this difference should be considered with patient age, severity of hyperthyroidism, goiter, ophthalmopathy, and future pregnancy plans (for young female patients).

Purpose: Radioiodine-131 treatment has been a well-established therapy for benign thyroid diseases for more than 75 years. However, the physiological reasons of the so-called stunning phenomenon, defined as a reduced radioiodine uptake after previous diagnostic radioiodine administration, are still discussed controversially. In a recent study, a significant dependence of thyroid stunning on the pre-therapeutically administered radiation dose could be demonstrated in patients with goiter and multifocal autonomous nodules. A release of thyroid hormones to the blood due to radiation-induced destruction of thyroid follicles leading to a temporarily reduced cell metabolism was postulated as possible reason for this indication-specific stunning effect. Therefore, the aim of this study was to develop dose-dependent correction factors to account for stunning and thereby improve precision of radioiodine treatment in these indications., Methods: A retrospective analysis of 313 patients (135 with goiter and 178 with multifocal autonomous nodules), who underwent radioiodine uptake testing and radioiodine treatment, was performed. The previously determined indication-specific values for stunning of 8.2% per Gray in patients with multifocal autonomous nodules and 21% per Gray in patients with goiter were used to modify the Marinelli equation by the calculation of correction factors for hyperfunctioning radiation-induced stunning (CHRIS). Subsequently, the calculation of the required activity of radioiodine-131 to obtain an intra-therapeutic target dose of 150 Gy was re-evaluated in all patients. Furthermore, a calculation of the hypothetically received target dose by using the CHRIS-calculated values was performed and compared with the received target doses., Results: After integrating the previously obtained results for stunning, CHRIS-modified Marinelli equations could be developed for goiter and multifocal autonomous nodules. For patients with goiter, the mean value of administered doses calculated with CHRIS was 149 Gy and did not differ from the calculation with the conventional Marinelli equation of 152 Gy with statistical significance (p = 0.60). However, the statistical comparison revealed a highly significant improvement (p < 0.000001) of the fluctuation range of the results received with CHRIS. Similar results were obtained in the subgroup of patients with multifocal autonomous nodules. The mean value of the administered dose calculated with the conventional Marinelli equation was 131 Gy and therefore significantly below the CHRIS-calculated radiation dose of 150 Gy (p < 0.05). Again, the fluctuation range of the CHRIS-calculated radiation dose in the target volume was significantly improved compared with the conventional Marinelli equation (p < 0.000001)., Conclusions: With the presented CHRIS equation it is possible to calculate a required individual stunning-independent radioiodine activity for the first time by only using data from the radioiodine uptake testing. The results of this study deepen our understanding of thyroid stunning in benign thyroid diseases and improve precision of dosimetry in radioiodine-131 therapy of goiter and multifocal autonomous nodules.

Objective: Initial treatment options for Graves' disease include antithyroid drugs, radioactive iodine (RAI), and surgery. Because of similar effects of three modalities, initial treatment preferences differ by country to country. In Korea, iodine-replete area, RAI was used as a second-line option. For these reasons, the RAI success rate in Korea might differ from other countries., Methods: A total of 247 patients were enrolled. The primary outcome was cumulative success rate in the first year, and the secondary outcome was factors that affected the success. Delayed response, which included patients who attained successful RAI during the follow-up, after the first year without further RAI, and factors that affected the delayed response were reviewed., Results: The cumulative success rate in the first year was 62.8%. Higher RAI activity [odds ratio (OR) 2.56, P = 0.02], longer disease duration (OR 0.43, P = 0.01), larger goiter (OR 0.31, P = 0.01), and higher post-RAI fT4 (fT4 between upper normal limit (UNL) to 1.5 × UNL; OR 0.24; P < 0.01, 1.5 × UNL<; OR 0.08; P < 0.01) were associated with RAI success. Twenty-seven patients showed delayed response, and goiter size (P < 0.05), pre-RAI TSH receptor Ab (TRAb) level (P < 0.01) and post-RAI fT4 (P < 0.01) were associated., Conclusion: The success rate of the first RAI in Korea was lower than that in other countries. Delayed response was observed in patients with smaller goiter, low pre-RAI TRAb, and low post-RAI fT4. In these patients, clinical follow-up with monitoring could be an option, and decision of optimal timing of first RAI is crucial.

Background and Aim: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4-50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease., Method: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n = 193) and patients treated with surgery as controls (n = 95). Data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. Results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index., Results: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers., Conclusion: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs of late effects of radioactive iodine on CIMT or plaque presence were found after 10 years of follow-up. The radiation to the carotid arteries by radioactive iodine therapy for benign thyroid disease may therefore have no or low effect on atherosclerotic burden of the carotid arteries in general.

Background and Purpose: Patient-reported outcomes have become important endpoints in comparative effectiveness research and in patient-centered health care. Valid patient-reported outcome measures detect and respond to clinically relevant changes. The purpose of this study was to evaluate responsiveness of the thyroid-related quality of life (QoL) instrument ThyPRO in patients undergoing relevant clinical treatments for benign thyroid diseases and to compare it with responsiveness of the generic SF-36 Health Survey., Methods: A sample of 435 patients undergoing treatment completed the ThyPRO and SF-36 Health Survey (Version 2) at baseline and 6 months after treatment initiation. Responsiveness was evaluated in three thyroid patient groups: patients with hyperthyroidism (n = 66) and hypothyroidism (n = 84) rendered euthyroid after medical therapy, and patients with a clinically detectable nontoxic goiter treated with surgery or radioactive iodine and remaining euthyroid (n = 62). Changes in QoL were evaluated in terms of effect size and compared to the changes predicted by clinical experts. The responsiveness of equivalent scales from ThyPRO and SF-36 Health Survey were compared with the relative validity index., Results: The ThyPRO demonstrated good responsiveness across the whole range of QoL aspects in patients with hyper- and hypothyroidism. Responsiveness to treatment of nontoxic goiter was also demonstrated for physical and mental symptoms and overall QoL, but not for impact on social life or cosmetic complaints, in contrast to clinicians' predictions. For all comparable scales except one, the ThyPRO was more responsive to treatment than the SF-36 Health Survey., Conclusions: The ThyPRO was responsive to treatment across the range of benign thyroid diseases. We suggest implementing this measurement instrument as a patient-reported outcome in clinical studies and in clinical management.

Introduction: The therapeutic effect of radioactive iodine ((131)I) on benign goitre consists of the emission of tissue-destructive beta-radiation. Since the range of beta (131)I radiation in tissue can reach 2.4 mm, it can affect the adjacent parathyroid glands. The purpose of this paper is to assess parathyroid function in patients with toxic and non-toxic goitres, up to five years following (131)I therapy., Material and Methods: The study sample consisted of 325 patients with benign goitres (220 with toxic nodular goitre (TNG), 25 with non-toxic nodular goitre (NTNG), and 80 with Graves' disease (GD) treated with (131)I. The therapeutic activity of (131)I for each patient was calculated using Marinelli's formula. The serum levels of fT3, fT4, TSH, iPTH and Ca(2+), Ca and phosphates were determined one week before (131)I administration, as well as every two months up to a year following the therapy, and then after three and five years post-treatment., Results: After two months following the administration of (131)I, all the treated patients showed a statistically significant above normal increase in iPTH concentrations (amounting to a value almost twice the norm in patients with TNG), which remained stable up to ten months after treatment, to return to normal level in the following months. In all the patients, Ca(2+), Ca, phosphates concentration remained within normal range throughout the course of the study. The concentrations of fT3 and fT4 quickly returned to normal after (131)I administration, and remained within normal range until the completion of the study., Conclusion: Radioiodine treatment of benign thyroid disorders results in transient (up to ten months after (131)I administration) hyperparathyroidism. The condition does not influence the level of calcium and phosphates concentration in any significant way.

Unlabelled: Radioactive iodine uptake (RAIU) is a test used to differentiate hyperthyroidism from thyroiditis and to calculate the radioiodine dose for treatment of Graves' disease. We aimed to evaluate the predictive role of 24h RAIU with respect to the outcome of radioiodine therapy in patients with diffuse toxic goiter (DTG)., Methods: Case records of patients with DTG treated with radioactive iodine were reviewed retrospectively. Patients were divided into two groups based on 24h RAIU (normal range: 15% - 35% at 24 h): the first group included patients with 24h RAIU values equal to or less than 50%, while the second group included patients with 24h RAIU values of over 50%. Gland size, duration of disease, treatment with antithyroid drugs (ATD) and its duration were the other factors considered. Success of the first dose of 131I was defined as a euthyroid or hypothyroid status at 12 months post-therapy without the need for additional radioiodine or ATD therapy. Data were analyzed with 95% power and 1% type I error (α=0.01)., Results: Six hundred thirty-three (633) consecutive patients with DTG were given a fixed-dose (5mCi) of radioiodine between January 1987 and December 2006. One hundred seventy-five patients (175) had an RAIU ≤50% and 458 patients had an RAIU >50%. First-dose success rate in the former group was 81.7% and in the second group 68.6% (p=0.001). The overall first-dose success was 72%. Multivariate analysis confirmed the significant role of 24h RAIU data to predict a successful outcome., Conclusion: A 24h RAIU value of ≤50% appears to be associated with a significantly better outcome compared to that of a 24h RAIU value of >50% in patients with DTG given as treatment a fixed dose of 185 MBq radioiodine.

An increased sensitivity of airport detectors, a growing number of isotopic tests, and globalization of the society have raised a number of false positive radioactive alarms at airports and public places. This paper presents two new cases of patients who triggered airport security alarms after receiving 740MBq of (131)I for non-toxic goitre and attempts to compare surprisingly limited literature concerning this problem. A 57-year-old man triggered a security alarm at three different airports on the 17th, 28th, and 31st day after radioiodine exposure. Interestingly enough, in the meantime, on the 18th and 22nd day, no radiation was detected in him at the airport where he was twice detained as a source of radiation later on. The second case presents a 45-year-old woman who activated security alarm detectors while crossing a border on her coach trip 28 days after radioiodine administration., (Copyright © 2011 Elsevier España, S.L. and SEMNIM. All rights reserved.)

We report the case of a 35-year-old nulliparous woman, with a previous history of ovarian cystectomy diagnosed 3 years earlier due a struma ovarii type of monodermal teratoma in the right ovary and a hemorrhagic cyst in the left ovary. Progressive growth of the left adnexal mass was observed in the periodic medical check-ups. Due to this, a second laparoscopy was performed and, based on the findings, a left ovarian cystectomy, right salpingectomy and resection of multiple peritoneal implants were carried out. The pathology diagnosis was left struma ovarii and peritoneal strumosis. A whole body and SPECT/CT scan with (99m)Tc-pertechnetate was performed to detect possible peritoneal implants. This study helped to make the therapeutic decision., (Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.)

Radioiodine therapy (RIT) for benign thyroid diseases in Germany requires the patient to stay in a nuclear medicine therapy ward for at least 48 hours and the dose to the thyroid to be computed from activity measurements performed during that stay. A major part of the total dose will be delivered after the patient's discharge from the hospital and thus has to be predicted through extrapolation with the effective half-life measured peri-therapeutically. We performed repeated thyroid uptake measurements on patients up to five months post therapy to investigate post-therapeutic changes in their effective half-lives and examine the dosimetric consequences. 12 patients (4 m, 8 f; age 36 - 76 y; 4 Graves' disease, 4 toxic adenoma, 3 toxic goitre, 1 non-toxic goitre) underwent late uptake measurements (1 - 7 meas., 13 - 154 d post administration, median 54 d, performed with thyroid probe resp. whole body counter at lower activities). Doses calculated from late measurements were compared to those predicted at discharge; half-lives calculated from the late measurement closest to the median delay (54 d) were compared to those determined at time of discharge. A cross-calibration between activity calibrator, thyroid probe, and whole body counter over an activity range from 52 MBq down to 45 Bq revealed linearity to within 6%, which was considered sufficient. In 9 out of 12 patients the achieved dose was within the range predicted at discharge. Averaged deviation between achieved and predicted dose was 3.1±2.2% (median 2.5%, range 0.7% - 7.2%). Averaged deviation between post- and peri-therapeutic half-lives was 5.1±3.9% (median 3.5%, range 1.3% - 12.5%). For n=5 patients discharged after 3 days, averaged deviations were greater (dose 4.0%, half-life 5.6%) than for those patients (n=7) who stayed in the hospital for a minimum of 4 days (dose 2.5%, half-life 4.8%). Excretion of iodine from the thyroid remains practically unchanged for at least two months after RIT. The dosimetric procedure implemented in our institution warrants a robust prediction of the post-therapeutic half-life and thus the actual achieved dose., (Copyright © 2011. Published by Elsevier GmbH.)

Objective: The purpose of this study was to clarify the efficacy of radioiodine (RI) therapy in Japanese patients with autonomously functioning thyroid nodules (AFTNs)., Methods: We performed a retrospective analysis to assess the management of AFTN patients. Thyroid lobectomy was performed to treat toxic adenoma (TA) patients, and total thyroidectomy to treat toxic multinodular goiter (TMNG) patients. RI therapy was administered in the form of a single dose (500 MBq) of isotope in the outpatient clinic. Percutaneous ethanol injection therapy (PEIT) was performed under ultrasound guidance., Results: Of the total 205 patients, consisting of 159 TA and 46 TMNG patients, 99 underwent surgery, 50 received RI therapy, and 56 received PEIT. Remission of thyrotoxicosis was achieved in all of the patients who were treated surgically. Hypothyroidism was documented in six of the 72 patients who were treated surgically other than by total thyroidectomy. Remission of thyrotoxicosis was observed in 43 of the 50 patients who were treated by RI therapy. Nine TA patients developed hypothyroidism during the follow-up period after RI therapy. Several PEIT sessions were required to achieve a remission of thyrotoxicosis. Remission of thyrotoxicosis was achieved in 29 of the 56 patients treated by PEIT, and thyrotoxicosis recurred in 17 these 56 patients., Conclusion: Surgery is the treatment of choice for large nodules and nodules that are resistant to other treatments, because it allows prompt control of thyrotoxicosis. RI therapy is a safe and effective means of controlling thyrotoxicosis in AFTN patients. We conclude that RI therapy is the treatment of choice for definitive treatment of AFTN patients who do not have local compression symptoms.

Radioactive iodine treatment is very frequently the best approach, but it should be optimized by dosimetric and risk considerations.

Background: There is little information about the individual safety instructions provided by healthcare professionals to patients receiving radioactive iodine (I-131) therapy for the treatment of benign and malignant thyroid disorders or about whether these instructions are consistent across medical specialties. Currently, no national guidelines exist to standardize safety instructions related to I-131 administration. Here, we examine the spectrum of I-131 safety practices in contemporary use., Methods: Members of major societies of physicians and allied specialists who treat patients with thyroid disorders were invited to complete a 27-question online survey about safety practices related to I-131 administration. Data from questionnaires were analyzed by type of safety recommendation and grouped according to provider specialty and geographic location., Results: A total of 311 endocrinologists, surgeons, nuclear medicine radiologists, and allied health professionals completed questionnaires. They indicated that patients often receive instruction from more than one treating specialist. The decision to hospitalize a patient for treatment and the length of stay were determined by the patient's social situation and the dose of I-131 administered. Starting at I-131 doses between 259 and 1073 MBq (7 and 29 mCi), over 60% of respondents advised avoiding contact with children, sexual activity, and breastfeeding, with the latter recommendation continuing beyond 48 hours after treatment. Personal hygiene, laundry, and meal preparation precautions varied across respondents. Over 90% of respondents used serum or urine testing to screen for pregnancy status. Precautions to delay parenthood were given more often to female than male patients (90% vs. 60%), with a minimum recommended delay of 6 months. About 20% of respondents considered insurance coverage as a factor in selecting outpatient versus inpatient I-131 therapy, and this consideration varied geographically., Conclusion: A wide variety of safety recommendations are given to patients who receive I-131. To our knowledge, this survey represents the first organized inquiry into safety practices related to I-131 administration. The diversity of responses suggests an opportunity for multispecialty collaboration in defining more uniform recommendations for patient safety instructions during and after I-131 treatment.

Aim: The use of radioiodine therapy is common in the treatment of benign thyroid disease. Council directive Euratom 97/43 requires that for all medical exposure of individuals for radiotherapeutic purposes exposures of target volumes should be individually planned. There are several strategies to accomplish this aim for radioiodine therapy including individual radioiodine uptake measurement and using either individual or mean effective radioiodine uptake and half-life. Although it is always simple to use standard activities, the effective thyroidal half-life and thyroidal uptake of I needs to be estimated individually to achieve optimal dosimetric results. We analyzed the radioiodine half-life and uptake in a large number of patients for use in a semi-individual calculation., Methods: Patients presenting consecutively between 1 January 2006 and 31 December 2007 were included in the study. Inclusion criteria were the control of hyperthyroidism and withdrawal of antithyroid drugs 2 days before preliminary radioiodine testing and therapy. Patients were treated for Graves' disease (n=363), nontoxic goitre (n=50), toxic goitre (n=639), or toxic uninodular adenoma (n=365). The effective half-life and uptake of I were estimated by uptake measurements after 24 h and 5 days during the preliminary radioiodine test, and serial measurements over 5 days during therapy., Results: The mean effective half-life of I measured during radioiodine therapy was 5.4 days in Graves' disease, 6.4 days in nontoxic goitre, 6.6 days in toxic goitre, and 5.7 days in toxic uninodular adenoma. The mean maximal uptake of I measured during radioiodine therapy was 64% in Graves' disease, 42% in nontoxic goitre, 38% in toxic goitre, and 31% in toxic uninodular adenoma., Conclusion: These actual values analyzed here might be used for a semi-individual calculation of therapeutic activity when an individual approach is not possible.

Selective pituitary resistance to thyroid hormones is a syndrome that involves inadequate response of thyroid-stimulating hormone to changes in thyroid hormones. Unlike generalized resistance syndromes, this entity produces central hyperthyroidism and clinical thyrotoxicosis. Sometimes the disease may not be properly diagnosed and is treated with drugs with harmful effects on the thyroid, such as amiodarone, hampering diagnosis and possibly exacerbating the disorder. The treatment of this condition can be symptomatic, based on control of tachycardia and anxiety, or etiological, acting on the pituitary to regulate thyrotropin secretion or on the thyroid gland to control thyroid hormone production. We report the case of a patient with pituitary resistance to thyroid hormone, who was treated with amiodarone to control paroxysmal atrial fibrillation.

Objective: To evaluate the effect of radioiodine therapy for volume reduction in large goitres., Methods: A retrospective study was performed involving 88 patients treated between 2001 and 2007 with radioiodine for toxic or nontoxic goitres. The goitres were between 80 and 250 ml in volume (median 127 ml+/-38.57). Activities of I to be administered were calculated individually through radioiodine testing with uptake measurements over 5 days, the mean activity being 1721+/-440 MBq I (714-2395 MBq I), equivalent to a mean of 14+/-4.19 MBq I/g of thyroid tissue (6-24 MBq I/g of thyroid tissue). The designated dose was 150 Gy for the entire thyroid volume, and post-therapeutic dosimetry revealed a mean thyroid dose of 175+/-45.92 Gy (64-300 Gy). Control examinations were performed, including thyroid blood testing and thyroid ultrasound at 6 weeks and at 3, 6, 12, 24, 36, 48 and 72 months after radioiodine therapy., Results: The mean volume reduction was 41.9% after 3 months and 65.9% after 1 year. Thyroid volume reduction was highly significant (P<0.001) in the first year after radioiodine therapy. No volume increase was observed in any patient during follow-up. Unfortunately, many patients were lost during follow-up (n = 84 after 3 months, n = 38 after 1 year)., Conclusion: Radioiodine therapy is an effective treatment for both nontoxic and toxic goitres, resulting in a highly significant thyroid volume reduction of nearly 66% within 1 year.

Unlabelled: Prestimulation with recombinant human thyroid-stimulating hormone (rhTSH) augments radioiodine (131)I therapy for benign nontoxic multinodular goiter. The purpose of this study was to determine the optimal time interval between rhTSH and (131)I administration to enhance thyroid radioactive iodine uptake (RAIU)., Methods: Patients were randomized, in a 2-factorial design, to receive either a 0.1-mg dose of rhTSH (n = 60) or placebo (n = 30) and to a time interval of 24, 48, or 72 h before (131)I administration. The rhTSH- or placebo-stimulated RAIU study was performed at 4 wk after a baseline RAIU assessment in a tertiary referral center at a university hospital. A total of 90 patients (78 women; median age, 52 y; range, 22-83 y) referred to (131)I therapy for symptomatic nontoxic goiter (median goiter volume, 63 mL; range, 25-464 mL) were included in the study. Change in thyroid RAIU was determined at 24 and 96 h after (131)I tracer administration., Results: In the placebo subgroups, RAIU did not change significantly from baseline. The mean (+/-SE) 24-h RAIU increased from 33.8% +/- 2.3% to 66.0% +/- 1.8% (111.2% increase) with a 24-h interval, from 36.8% +/- 2.1% to 64.6% +/- 2.7% (83.3% increase) with a 48-h interval, and from 33.0% +/- 2.7% to 49.6% +/- 2.5% (62.4% increase) with a 72-h interval. All within-group changes were highly significant (P < 0.001). The effect was negatively correlated with initial RAIU (r = -0.703, P < 0.001). The increase in 24- and 96-h RAIU was significantly higher in the rhTSH/24-h group than it was in the rhTSH/72-h group (P = 0.023 and 0.012, respectively) and insignificantly higher than in the rhTSH/48-h group (P = 0.37 and 0.26, respectively)., Conclusion: The effect of rhTSH on thyroid RAIU is most pronounced when administered 24 h before (131)I administration and declines with longer time intervals. Whether there is a similar time dependency for goiter reduction after rhTSH-stimulated (131)I-therapy remains to be clarified.

Objective: To evaluate the efficacy of radioiodine therapy using I in a group of patients with large multinodular goitre (LMG)., Methods: The study was carried out in patients with goitre volume greater than 100 cm and in patients with LMG who were disqualified from surgery. The study included 34 female participants (age range: 62-84 years) with LMG: 26 patients were hyperthyroid and eight patients had a nontoxic goitre. The patients were treated with 800 MBq of radioiodine administered four times at 3-month intervals (total activity of 3.2 GBq). Before each therapy course, serum thyrotropin, free thyroxin, free triiodothyronine and antithyroid antibodies were measured, ultrasonography and thyroid scan were performed. Patients were followed up for a minimum of 24 months. Fine-needle biopsy was done before qualification to the study., Results: Before therapy, median thyroid volume was 145 cm. It decreased during therapy to 65-76 cm after 12 months and to 50-62 cm after 24 months. After 24 months, 60% of patients were euthyroid and 40% of patients were hypothyroid. During therapy, significant increases in TSHRAb, TPOAb and TgAb levels were observed. No correlation between the levels of antithyroid antibodies, radioiodine uptake, reduction of goitre volume and hormonal status was found., Conclusion: In most cases of LMG, repeated administration of radioiodine is safe and effective. The highest response of the thyroid volume is observed after the first course of treatment. On account of a high incidence of hypothyroidism, the patients should be monitored during and after therapy.

Context: There is little consensus regarding the most appropriate dose of radioiodine ((131)I) to be administered to patients with hyperthyroidism., Objective: To compare the efficacy of fixed dose regimens of (131)I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients., Design: Consecutive series of hyperthyroid subjects treated with (131)I., Setting: Single Secondary/Tertiary Care Hospital Clinic., Participants: A total of 1278 patients (1013 females and 262 males, mean age 49.7 years) presenting with hyperthyroidism between 1984 and 2006., Intervention: Treatment with (131)I using a fixed dose regimen., Main Outcome Measures: Probability of cure and risk of development of hypothyroidism following a single dose of (131)I., Results: Patients given a single dose of (131)I of 600 MBq (n = 485) had a higher cure rate (84.1%) compared with those receiving either 370 MBq (74.9%, P < 0.001) or those given 185 Bq (63%, P < 0.001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60.4%; 370 MBq: 49.2%, P = 0.001; 185 Bq: 38.1%, P < 0.001). Binary logistic regression analysis identified a 600 Bq dose of (131)I [adjusted odds ratio, AOR 3.33 (2.28-4.85), P < 0.001], female gender [AOR 1.75 (1.23-2.47), P = 0.002], lower presenting serum free T4 concentration [AOR 1.01 (1.01-1.02), P < 0.001] and absence of a palpable goitre [AOR 3.33 (2.00-5.56), P < 0.001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3.79 (2.66-5.38), P < 0.001], female gender [AOR 1.46 (1.05-2.02), P = 0.02], younger age [AOR 1.03 (1.02-1.04), P < 0.001], absence of a palpable goitre [AOR 3.85 (2.38-5.88), P < 0.001] and presence of ophthalmopathy [AOR 1.57 (1.06-2.31), P = 0.02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived., Conclusions: Simple clinical/biochemical criteria can be used to predict outcome after (131)I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure.

Introduction: Amiodarone (AM) is frequently used in the therapy of patients with cardiac disorders. However, due to high iodine content, it has side effects on thyroid function. The use of radioiodine therapy (RIT) in amiodarone-induced thyrotoxicosis (AIT) with low radioactive iodine uptake (RAIU) is still controversial. In these patients therapeutic choices for refractory disease include surgery, antithyroid drugs, or glu ocorticosteriods., Aim: The aim of the study was to evaluate the efficacy of RIT in patients presenting AIT and low RAIU in two-year follow-up., Patients and Methods: 40 patients (25 men and 15 women) aged from 63 to 83 years (x +/- SD: 66.2 +/- 5.0 years; median: 65 years) treated with RIT were included into the study. In these patients AM therapy was essential for the underlying heart disorder, while surgery, antithyroid drugs or glucocorticosteroids, were contraindicated. Forty seven patients with toxic multinodular goiter (TMNG) (39 women and 8 men), matched for age (67 +/- 12 yr; range 54-89 yr), were enrolled into the study as a comparative group. The diagnostic procedures included baseline thyroid function tests (thyrothropin - TSH, free triiodothyronine - fT3 and free thyroxine - fT4 levels), thyroid autoantibodies measurement (antithyroglobulin autoantibodies - TgAb, antithyroid peroxidase autoantibodies - TPOAb, anti-TSH receptor autoantibodies - TRAb), thyroid ultrasonography, thyroid scintiscan and RAIU assessment., Results: Serum values of TSH, TgAb, TPOAb and TRAb were undetectable in both groups. In patients with AIT fT4 level was 18.7 to 38.7 pmol/l (mean: 27.1 +/- 5.8) and fT3 concentration was 3.9 to 5.6 pmo/l (mean: 5.7 +/- 1.4), while in TMNG patients level of fT4 was 31.5 to 22.2 pmol/l (mean: 25,3 +/- 5,8) and fT3 concentration was 3.8 to 4,2 pmo/l (mean: 4,2 +/- 0,2). Mean RAIU values after 5h and 24h in AIT patients were 2.3 +/- 0.5 and 3.1 +/- 0.9%, while in TMNG patients were 18,0 +/- 3,8 and 35,7 +/- 9,1%, respectively. A significant difference (p<0.001) between 5h and 24h RAIU in AIT compared to TMNG was noted. In all patients with AIT, a dose of 800 MBq of 131I was administered. During two-year-observation recurrence of hyperthyroidism was observed in two patients (5%) with TMNG. These patients received a second radioiodine dose 16.2 +/- 15 months later (the mean re-treatment dose was 735.93 +/- 196.1 MBq). In comparison, none of the patients with AIT required a second 131I dose and only one patient (2.5%) 6 months after ablative 131I dose needed anti-thyroid medication. Transient hypothyroidism was observed in only two patients (5%) with AIH, though was not observed in TMNG. During follow-up time, no sudden deaths in AIT patients were observed; one patient was diagnosed with prostate cancer, and in one patient acute toxic hepatitis after AM occurred., Conclusion: RIT may be a safe and useful method of AIT therapy in patients with low RAIU, in whom other treatment methods are contraindicated.

Background: A survey of physicians' practice relating to radioiodine administration for hyperthyroidism was carried out in the UK over 15 years ago and showed wide variations in patient management. This led to the development of national guidelines for the use of radioiodine in hyperthyroidism. As there have been significant advances in the field since that survey, we carried out another survey to study the prevalent practices relating to radioiodine therapy for benign thyroid disorders across the UK., Subjects and Methods: We mailed 698 UK consultant endocrinologists a questionnaire on radioiodine treatment based on three patient scenarios: hyperthyroid Graves' disease, subclinical hyperthyroidism and nontoxic goitre., Results: The response rate was 40%. For the scenario of an initial presentation of Graves' disease, 80%, 19% and 0.4% of respondents preferred thionamide, radioiodine or thyroidectomy, respectively. There were inconsistencies in respondents' recommendations on radioiodine dose, the use of pre- and post-radioiodine supplementary treatments, timing of a repeat dose, and the use of radioiodine in thyroid eye disease. For the case of subclinical hyperthyroidism, one-third of respondents would generally initiate treatment. The majority were more likely to treat subclinical hyperthyroidism in the presence of paroxysmal atrial fibrillation or osteoporosis. If a decision were made to treat subclinical hyperthyroidism, 63%, 35%, 1% and 0.4% would recommend radioiodine, thionamide, beta-blocker and thyroidectomy, respectively. For the scenario of nontoxic goitre, 62%, 21%, 13% and 5% favoured observation, thyroidectomy, radioiodine and thyroxine, respectively., Conclusions: There remain significant differences in several aspects of clinical practice relating to the use of radioiodine treatment for benign thyroid disorders in the UK.

Radioiodine (131 I) therapy has been in use for more than 60 y. Several protocols have been suggested and used for prescribing the activity to be administered to the patients for the treatment of hyperthyroidism; application of these protocols may result in an under or over dose of the hyperthyroid patients. The main objective of this study was to carry out quantitative analysis of the factors responsible for possible under or over dosage of the patients. In this regard, a total of 59 patients [15 diffuse goitre (DG) and 44 nodular goitre (NG) cases] were studied. In order to compare the thyroid doses calculated by using different protocols, the dosimetric approach was followed. 131 I uptakes were measured after 24 and 48 h, respectively, by giving 0.5 MBq of 131 I to each patient. Thyroid mass and effective half-life were also calculated for each patient and the variations in the thyroid doses were analysed. According to the results 28 and 54% patients were under dosed and 72 and 46% patients were over dosed with DG and NG, respectively. The protocols, which have not taken into account the thyroid mass, multi pre-therapeutic 131 I uptakes and the effective half-life of 131 I of the individual patient, showed a higher degree of deviation from the required thyroid dose. Besides these parameters, some fundamental factors such as radiosensitivity, previous exposure to thyroid drugs and duration of the disease are recommended to be incorporated, which can certainly affect the clinical out comes.

Introduction: The effect of (131)I therapy amplification by recombinant human (rh) TSH prestimulation in very large goiters has not been evaluated in a double-blinded, placebo-controlled study., Methods: Twenty-nine patients (22 females; age range 37-87 yr) with a large multinodular goiter (median 160 ml, range 99-440 ml) were randomized to receive placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I administration. Goiter volume was monitored by magnetic resonance imaging., Results: On average, the goiter volume was unchanged 1 wk after therapy in both groups, but the largest deviations from baseline were observed in the rhTSH group. After 12 months the median goiter volume was reduced from 170 to 121 ml in the placebo group and from 151 to 72 ml in the rhTSH group, respectively (within group: P = 0.001; between group: P = 0.019). This corresponds to reductions of 34.1 +/- 3.2 and 53.3 +/- 3.3%, respectively (between group: P < 0.001). In the placebo group, the goiter reduction correlated positively with the retained thyroid (131)I dose, whereas such a relationship was absent in the rhTSH group. Adverse effects, mainly related to thyroid pain and cervical compression, were more frequent in the rhTSH group. At 12 months, goiter-related complaints were significantly reduced in both groups without any between-group difference. One and three patients in the placebo and the rhTSH group, respectively, developed hypothyroidism., Conclusion: rhTSH-stimulated (131)I therapy improves the reduction of very large goiters by more than 50%, compared with (131)I therapy alone, but at the expense of more adverse effects after therapy. Our data suggest that rhTSH stimulation may work through mechanisms that go beyond the increase in thyroid (131)I uptake.

Context: Hashimoto's thyroiditis is an autoimmune disease that can produce marked clinical symptoms when patients have large diffuse goiters., Design: This retrospective cohort study was designed to evaluate whether radioactive iodine (RAI) is effective for Hashimoto's thyroiditis with a large goiter. Starting in November 1999, 13 Hashimoto's patients with large goiters, whose thyroiditis was refractory to TSH suppression therapy with thyroid hormone administration [two men and 11 women with a mean age of 61.2 +/- 8.9 yr (50-79 yr)], were recruited for the present study. The duration of symptomatic goiter before undergoing RAI was 12.0 +/- 7.9 yr (4-33 yr). Thirteen millicuries of 131I was administered two to six times, at an interval of 1-6 months on an outpatient basis. Thyroid weight was measured ultrasonographically, or by computed tomography if ultrasound was not possible due to the large size of the goiter., Results: RAI was administered an average of 4.7 +/- 1.4 times (two to six times), with a total dose of 59.8 +/- 17.3 mCi (25.0-78.0 mCi). The observation period was 47.9 +/- 13.4 months (26-66 months) after the first RAI. The average weight of the thyroid gland was 125.3 +/- 57.7 g (42.9-269.4 g) before the first RAI, decreasing significantly to 49.7 +/- 25.8 g (18.3-93.3 g) after the last RAI (P < 0.001, paired Student's t test). The percent reduction from baseline was 58.7 +/- 14.2% (35.7-84.0%). None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments., Conclusion: RAI is effective in Hashimoto's thyroiditis with a large goiter.

Objective: When using radioiodine for hyperthyroidism there is no consensus regarding the administration of fixed or calculated doses. Guidelines do not specify the preferable approach or the parameters to use to calculate the dose. Therefore, the dose might be quite different with regard to the chosen procedure. This study was undertaken to evaluate the variability of the amount of radioiodine administered in Belgium in various cases of hyperthyroidism., Design and Patients: Twenty-one Belgian nuclear medicine physicians received summarized clinical files from 10 patients suffering from overt hyperthyroidism (n = 7) or subclinical hyperthyroidism (n = 3). Five patients had homogeneous goiters, one had multinodular goiter, and four had hot nodule. Participants had to determine the radioiodine dose (millicuries, mCi) they would give in each case., Results: Proposed doses varied between 2 mCi and 25 mCi. Mean proposed dose for nodular disease was 10.71 mCi; it was 6.79 mCi for homogeneous goiter. For individual cases, a difference between the lowest and the highest dose of more than 17 mCi was observed in more than 50% of the cases., Conclusions: We believe that more precise guidelines are mandatory, underlying uncertainties, controversies but recommending however, as minimal and maximal doses to administer, as well as clinical and biological parameters, if any, to be taken into account in order to modulate these doses.

Objective: According to European recommendations, the external dose rate (ED) in radioiodine-treated goitre patients can be determined by estimating from calculation of the residual activity (RA) in the patient based on radioiodine uptake measurements or by measuring ED directly. In the European guidelines, "Radiation Protection 97", it is assumed that an RA of 600 MBq (131)I causes an ED of 30 microSv/h at a distance of 1 m. This implies a slope of 0.05 microSv/h/MBq for the ratio ED/RA relationship, but, theoretically, this ratio is higher, at 0.07, a difference that is due to measurement in air versus in a scattering medium. We sought to investigate what the true ratio might be., Material and Methods: Sixty-six patients scheduled for radioiodine treatment of benign goitre (mean size 102 mL, range 20-440), who received (131)I orally (mean 984 MBq, range 173-3700) were examined. After 24 h and 96 h iodine uptake percentage we examined 7269 patients scheduled for radioiodine treatment of benign goitre (mean size 1042 mL, range 20-440) who received (131)I orally (mean 101,100 MBq, range 180-3700). After 24 h and 96 h, the iodine uptake was determined, RA calculated and ED measured using a hand-held dosimeter., Results: At 24 and 96 h, we observed a slope ratio of 0.103 microSv/h/MBq (95 % CI: 0.09564-0.111) and 0.101 microSv/h/MBq (95 % CI: 0.0915-0.11107), respectively, for the ED/RA relationship. None of the confidence intervals included the value 0.05 microSv/h/MBq, reflecting that the observed slopes differed significantly from the expected slope (p < 0.001). Consequently, an RA of 600 MBq typically causes an ED of 60 and not 30 microSv/h, and therefore dose rates based on radioiodine uptake measurements and established assumptions were only about half as high as the directly measured values. We noticed that with an RA roughly below 450 MBq, the anticipated slope of 0.05 microSv/h/MBq is within the prediction interval of our claimed ratio, therefore we cannot rebut the anticipated slope for lower doses., Conclusions: Dose-rate estimates based on radioiodine uptake measurements and established assumptions were only about half as high as the directly measured values in patients receiving doses higher than the widely accepted limits for outpatient treatment. This finding may have substantial implications for us, in that it makes a considerable difference whether the radiation precautions are taken to limit doses to the patient's surroundings and for deciding if a patient may or may not be regarded as an outpatient, as well as for the safe discharge of an inpatient from hospital.

Objective: The purpose of this retrospective study was to evaluate the incidence of recurrence and the success of radioiodine treatment (RIT) in the Trakya region of Turkey, an area with mild iodine deficiency, and to compare the effect of dose regimen selection (fixed (FD) or calculated dose (CD)) on treatment success., Material and Methods: The study sample included 148 patients (40 male, median age 50) treated with radioiodine between the years 1991-2003. Patients were categorized into three diagnostic groups: Graves' disease (GD) (n = 65), solitary toxic adenoma (TA) (n = 29), and toxic multinodular hyperthyroidism (TMH) (n = 54), and each divided into two subgroups according to treatment method; the first group was treated with a FD of 370 MBq (10 mCi), and the second with CD., Results: The largest group was GD (44%), followed by TMH (36%). Median duration of follow-up was 28 months (range 6-147). FD was given to 52.7% of all patients and CD was given to 47.3%. There was a partial difference in the dose regimen between all groups, but did not reach statistically significant levels (FD vs. CD: 65%-35%; 38%-62%; 46%-54%; GD, TA, TMH respectively, p > 0.05). Total cure rate in FD and CD was 46 (59%) and 37 (52.9%), respectively. The rates of hypothyroidism for GD, TA, and TMH groups were 28 (43.1%), 6 (20.7%) and 16 (29.6%), respectively. The incidence of hypothyroidism did not vary significantly between any groups (p > 0.05). At the end of the follow-up period, a total of 104 patients (70.3%) were treated successfully. There was no significant difference in the cure rate between any groups (p > 0.05)., Conclusions: The treatment success in all groups and subgroups did not differ significantly between FD and CD. Our lower cure rate than in previous studies may be related to iodine deficiency. Higher doses of radioiodine may be required to increase final treatment success in endemic goiter areas. If this true, dosimetry and calculated dose regimen would be required in all groups of patients instead of an FD concept. However, our findings should be verified in larger series of patients, with longer follow-up period, and urinary iodine concentration measurements.

Introduction: Iodine uptake and the effect of radioiodine treatment of nontoxic goiter were investigated after the introduction of iodine to salt., Materials and Methods: A retrospective study was done of 61 patients (48 women and 13 men with a median age of 56 (range 28-78)) with nontoxic goiter, examined by 24-hour radioiodine uptake. 42 of the patients were treated with radioiodine (median 600 MBq, range 200-600 MBq). The results were compared with those from a study done 10 years ago in the same area., Results: Iodine uptake decreased significantly, from 40% (range 16-67%) in 1981-1993 to 25% (range 13-62%) in 2001-2003. 38 of the 42 patients were examined, and of these 34 (90%) had benefited from the treatment (53% of the 38 patients showed a complete effect) as estimated by the patient and the physician, based on the patient's original symptoms and the physician's clinical judgement. Four patients developed hypothyroidism, one radiation-induced thyroiditis and three Graves" disease., Discussion: Iodine uptake is significantly lowered after the addition of iodine to salt. Radioiodine therapy of nontoxic goiter will continue to be effective.

Objectives: Patients treated by (131)I may require blood sampling in the days following its administration. We investigated the safety of such samples in terms of radioactivity and the possible disturbance of the analyses by these "131I-spiked" samples., Method: 1) The radioactivity of blood samples from 131I-treated patients was measured (dose rate, surface activity, total activity) ; 2) The risk for the personnel was subsequently evaluated and ; 3) The interference of this 131I-generated radioactivity on the results of routine automated and IRMA assays was investigated., Results: 1) All RA measures but two were found below the European limits ; 2) Irradiation of personnel was negligible ; 3) The faint radioactivity did not disturb any analyses., Conclusion: These data demonstrate the safety that results from the negligible radioactivity in these blood samples.

Objective: To evaluate the effect of dose rate on the therapeutic success of radioiodine therapy (RIT) by retrospective analysis of two groups of patients with different dose rates during RIT., Methods: The average dose rate until deposition of 50% of the total radiation dose achieved (the DL50 value) was calculated. Ninety patients with autonomy of the thyroid receiving radiation doses between 300 and 400 Gy were separated in groups with high DL50 values (the DL50 H group) and low DL50 values (the DL50L group). Before and 4 months after RIT free triiodothyronine (FT3), free thyroxine (FT4), basal thyroid stimulating hormone (TSHB), stimulated TSH (TSHS), thyroidal technetium uptake (TcTU), and the existence of focal abnormalities in thyroid scintigraphy were evaluated., Results: The DL50 H and DL50L groups showed no differences before RIT in the parameters assessed as well as in total achieved dose and autonomous thyroid volume. After therapy a significant difference was found in TSHB with higher values in DL50 H (1.89+/-1.49 vs. 1.31+/-1.48 mU . l, P<0.05), FT4 showed a trend to lower values (13.8+/-4.0 vs. 16.1+/-6.2 pmol . l, P=0.09)., Conclusion: The DL50 value has an influence on therapeutic success of RIT. This influence is only discrete and not likely to produce clinically relevant effects in the practical use of RIT.

Objective: To investigate the long-term effects of continuous methimazole (MMI) therapy., Design and Methods: Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continuous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained., Results: There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treatment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12-2.95, P<0.02) and 1.6 (1.09-2.34, P<0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups., Conclusion: Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.

Objective: To evaluate the therapeutic efficacy and safety of iodine-131 therapy for large goiter complicated by hyperthyroidism., Methods: After the diagnosis of large goiter complicated by hyperthyroidism was established, the weight of the patient's thyroid gland was determined, and the doses of iodine-131 calculated according to the formula currently available. After a single dose of oral iodine-131 capsule, the patients were observed for the therapeutic efficacy and side effects. Some patients were given the second or even the third dose of iodine-131., Results: All of the 38 patients were cured by 1 to 3 single doses of iodine-131 therapy, of whom 23 (60.5%) needed only a single dose for the cure, 13 (34.2%) required the second dose, and 2 (5.3%) necessitate a third dose. Hypothyroidism occurred in 4 cases (10.5%), and none of the patients developed hyperthyroidism crisis and dyspnea., Conclusions: Iodine-131 therapy for serious goiter with hyperthyroidism is safe and effective, which can be used as a routine therapy for this condition.

Objective: To report the effects of pretreatment with recombinant human thyrotropin (rhTSH) on radioiodine uptake (RAIU) and subsequent radioiodine therapy in 30 patients with symptomatic nontoxic or toxic multinodular goiter., Methods: Patients received a single injection of rhTSH (0.1 mg in 21 and 0.3 mg in 9 patients). Thyroid function tests were performed before and 72 hours after rhTSH administration. Both 4-hour and 24-hour RAIU studies were done after rhTSH administration and repeated at 48 to 52 hours and at 72 hours, respectively. Then all patients were treated with 30 mCi of 131 I., Results: All study patients experienced symptomatic relief by 1 to 2 months. In addition to the previously reported twofold increase over the baseline RAIU at 24 hours, we found that a second 24-hour RAIU showed a further twofold increase (quadrupling of the RAIU over baseline) at 72 hours after administration of 0.1 mg of rhTSH (from 22% to 43%; P<0.001) and 0.3 mg of rhTSH (from 16% to 37%; P = 0.002), with no significant difference between doses on the RAIU at 24 hours or at 72 hours. Additionally, the RAIU value at 4 hours and 52 hours after administration of 0.1 mg and 0.3 mg of rhTSH revealed a fourfold increase for each dose--from 7% to 28% (P<0.001) and from 5% to 21% (P = 0.002), respectively., Conclusion: In patients with symptomatic toxic or nontoxic multinodular goiter, 0.1 mg and 0.3 mg of rhTSH were equally efficacious at inducing a quadrupling of the low or low-normal baseline RAIU values at 72 hours after injection. Subsequent radioiodine therapy alleviated compressive and thyrotoxic symptoms in all 30 treated patients. Future studies should help determine doses of rhTSH and radioiodine therapy that are optimal in iodine-sufficient and insufficient regions of the world.

Low-iodine diet has been employed to achieve iodine depletion prior to radioiodine (RI) therapy. However, treatment with diuretics may be more effective than low-iodine diet in causing iodine depletion and subsequent increase in RI uptake by the thyroid. Fifty-five patients with non-toxic goitre were given 0.20 MBq RI p.o. on the first day of the study and thyroid uptake was measured. In 15 patients, a low-iodine diet was started and continued for 14 days. The remaining 40 patients received furosemide 40 mg/day orally for 5 days with an unrestricted diet. On the 15th day of the study, all patients were given 0.20 MBq RI p.o. and thyroid RI uptake was measured again. Additionally, 24-h urinary iodine excretion and RI clearance were measured on the 1st and 6th days in 21 patients from the furosemide group and on the 1st and 15th days in eight patients from the diet group. Furosemide administration led to a 58.40% increase in iodine uptake over the baseline value, which was significantly higher than the increase caused by low-iodine diet (17.22%) ( P<0.0001). Urinary excretion of RI decreased in both groups similarly (furosemide, 29.45%; low-iodine diet, 21.06%; P=0.33). Iodine clearance also decreased in each group similarly (10.61% vs 7.53%, P=0.53). Treatment with furosemide prior to administration of RI increases the uptake of RI by the thyroid more effectively than does low-iodine diet.

In routine use for more than 50 years, radioiodine ((131)I) is generally considered safe and devoid of major side effects. Therefore, it is surprising that relatively many aspects of radioiodine therapy are controversial, as illustrated by recent international questionnaire studies. Our review aims at highlighting three of these areas - namely, the influence of (131)I on the course of Graves' ophthalmopathy, the possible radioprotective effects of antithyroid drugs, and the use of (131)I in large goitres. (131)I therapy carries a small (but definite) risk of causing progression of Graves' ophthalmopathy. Identification of risk factors (thyroid dysfunction, high level of thyroid-stimulating hormone (TSH) receptor antibodies, cigarette smoking) allows the identification of patients at risk and the institution of concomitant glucocorticoid treatment, thereby hindering progression of eye disease. On the basis, largely, of retrospective data, it appears that carbimazole (or methimazole), if stopped 3-5 days before treatment, does not influence the outcome of (131)I therapy. Simultaneous thyrostatic medication most probably reduces the efficacy of (131)I, as does restarting it within 7 days. Propylthiouracil seems to have a more prolonged radioprotective effect than carbimazole. Surgery is the treatment of first choice in patients with a large goitre. However, in the case of patient ineligibility or preference, (131)I therapy may be an option. The treatment has a favourable effect on tracheal compression and inspiratory capacity, but the reduction in thyroid volume is only 30-40%. Inpatient treatment, necessitated by the large doses, makes the treatment cumbersome. Controversy related to radioiodine therapy is mainly based on the lack of adequate prospective randomised studies comparing efficacy, side effects, cost and patient satisfaction.

Objective: To evaluate the role of lithium (Li) as an adjuvant in radioiodine therapy of hyperthyroidism., Methods: A randomized controlled trial was carried out on 350 hyperthyroid patients with a mean follow-up period of 32.3 +/- 9.8 months (range, 12-60 months). The patients were randomized into two groups with 175 patients in each group: (1) radioiodine group (controls)-no lithium was given to these patients at any stage of their treatment and (2) radioiodine and lithium group (Li group)-lithium carbonate, 300 mg three times a day, for 3 weeks starting on the day of radioiodine administration. All patients were made euthyroid with antithyroid drugs prior to radioiodine therapy., Results: Mean age was 41.8 +/- 11.5 years (range, 18-71) in the control group and 41.8 +/- 12.2 years (range, 19-73) in the Li group. Mean first dose and cumulative dose of (131)I were 229 +/- 85 MBq and 326 +/- 204 MBq in controls and 233 +/- 110 MBq and 344 +/- 281 MBq in the Li group. Average number of radioiodine therapy administered was the same (1.4) in both groups. The cure rate (euthyroid plus hypothyroid) after the first dose of radioiodine in the control and the lithium groups was 68.4% and 68.9%, respectively (p = ns). The overall cure rate at the end of the study was also the same in both groups (96.7% and 96.3%, respectively). Even in patients with a rapidly discharging gland or in patients with a large goiter, no significant statistical difference was observed in radioiodine therapy outcome between the two groups. Ten percent of the patients complained of mild to moderate side effects of lithium., Conclusion: The role of lithium as an adjuvant in radioiodine therapy of hyperthyroidism is insignificant.

Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.

Graves' disease is the most common form of hyperthyroidism in childhood. Current treatment options include antithyroid medications, surgery, and radioactive iodine. Medical therapy is generally associated with long term remission rates of less than 25% and a small risk of serious adverse reactions that include hepatic failure and bone marrow suppression. Total thyroidectomy is associated with very high cure rates and a small risk of hypoparathyroidism and recurrent laryngeal nerve damage. When radioactive iodine is used at appropriate doses, there is a very high cure rate without increased risks of thyroid cancer or genetic damage. Because of the theoretical risk of thyroid cancer after thyroid irradiation in individuals less than 20 years of age, relatively high doses of radioactive iodine should be administered to minimize the persistence of residual thyroid tissue.

Radioiodine is used to treat thyroid cancer and hyperthyroidism. In order to reduce radiation hazard to the patient and to people in contact with the patient it would be desirable to obtain the same therapeutic effect with lower activities of the radioisotope. This could be achieved by the simultaneous administration of a compound that increases tissue radiosensitivity. In this study we analyzed the use of nicotinamide (NA) as a radiosensitizer to radioiodine, to increase 131I efficacy. NA administered during 30 days to Wistar rats failed to alter thyroid weight. The influence of NA on radiothyroidectomy induced by increasing doses of 131I was examined in otherwise nontreated rats. NA produced a significant increase in the ablation caused by radioiodine. Goiter was then induced by the administration of methylmercaptoimidazol (MMI) to rats, followed by the treatment with radioiodine with and without simultaneous administration of NA. Thyroid weight per 100 g of body weight ratio was not changed by NA alone; 131I administration caused a 25% decrease in goiter size, while 131I plus NA produced a reduction of the ratio of 46% (p < 0.01 vs. NA). No changes were observed in adenosine diphosphate (ADP)-ribosilation of thyroid nuclear protein in NA-treated rats. Thyroid blood flow (determined by 86Rb uptake) was increased by 84% by NA. In conclusion, nicotinamide has a significant radiosensitizing effect to 131I both in normal and goitrous rats. This action is because of an increase in thyroid blood flow, which probably enhances tissue oxgenation.

Objective: Hyperthyroidism has profound effects on the cardiovascular system, including reduced systemic vascular resistance (SVR) due to relaxation of vascular smooth muscle cells, enhanced heart rate (HR) and cardiac output (CO) due to an increase in cardiac diastolic relaxation, contractility and heart rate. Subclinical hyperthyroidism is characterised by reduced serum TSH levels despite free thyroxine (T4) and tri-iodothyronine (T3) estimates within the reference range, in subjects with no obvious symptoms of hyperthyroidism. We measured haemodynamic changes (using impedance cardiography) in subjects with endogenous subclinical hyperthyroidism in order to elucidate whether these patients had signs of excess thyroid hormone at the tissue level., Design: The patients were otherwise healthy women with a multinodular goitre (n=6; age 47-81 years; serum TSH 0.006-0.090 mU/l and normal free T4 and T3 estimates), studied before and after normalisation of TSH (0.280-1.120 mU/l) by means of radioiodine treatment, and they were compared with 9 overt hyperthyroid patients (2 with multinodular goitre and 7 with Graves' disease) in the untreated state and after euthyroidism had been obtained., Results: Treatment of the subclinical hyperthyroid women resulted in 11% reduction in HR (P<0.02), 19% reduction in CO from (means+/-s.d.) 6.93+/-2.15 l/min to 5.58+/-1.94 l/min (P<0.05), and 30% increase in SVR (P<0.02). Similar but more pronounced changes were seen in the hyperthyroid group: 17% reduction in HR, 25% reduction in CO and 46% increase in SVR (all at least P<0.05). Taking all 15 patients together, thyroid function (as measured by free T3 index (FT3I) or TSH) correlated significantly to the haemodynamic parameters as follows: the higher the thyroid function the lower the mean arterial pressure and SVR, and the higher the CO and central aortic compliance (stroke volume/pulse pressure) (P<0.05). Plasma norepinephrine increased significantly after treatment of the overt hyperthyroid patients, whereas epinephrine did not change, and no changes were seen among subclinical hyperthyroid patients., Conclusion: Treatment of endogenous subclinical hyperthyroidism resulted in significant changes in several haemodynamic parameters regarding the heart and the vascular system, compatible with some degree of excess tissue exposure to thyroid hormones in the untreated state. Our data favour more aggressive treatment of these patients, and endogenous subclinical hyperthyroidism might be regarded as a mild form of hyperthyroidism.

Purpose: It has been reported that the effect of radioactive iodine (RAI) treatment is complete in 4 to 6 months. This retrospective study evaluated the appropriate time for repeated treatment of hyperthyroid disease with RAI after initial treatment failure., Methods: Outcomes of 128 patients treated with RAI for hyperthyroid disease were reviewed retrospectively at 3 and 6 months., Results: Eighty patients (group A) were treated successfully with a single dose of RAI. Twenty patients (group B) required a second treatment dose. Twenty-eight patients were lost to follow-up. All patients in group A were clinically improved to various degrees at 3 months and continued to improve at 6 months. All eight patients in group B who showed no improvement at 3 months remained the same at 6 months. The difference between the two groups was statistically significant., Conclusion: Patients with hyperthyroid disease who are unimproved at 3 months can be retreated with RAI without further delay.

The aim of this study was to investigate the equivalence in outcome of standardized versus uptake-adjusted dosing of radioactive iodine (131I) for hyperthyroidism. We performed a 1-year follow-up study of two patient cohorts: 326 patients referred for 131I treatment of hyperthyroidism in Graves' disease (GD; n=216) or toxic multinodular goitre (TMG; n=110) in the period June 1995 to January 1998. Of these patients 128 were treated according to a standardized regimen, based on palpated thyroid volume and diagnosis, and 198 with a 131I uptake-adjusted dosimetric method. The incidence of hypothyroidism, euthyroidism or recurrence of disease was recorded. In Graves' disease hypothyroid outcome in the standardized versus adjusted method was 40.7% vs 44.6% (95% CI difference, -17.4 to +9.5%); it was 67.4% vs 70.8% (95% CI difference -15.9 to +9.3%) for all non-euthyroid outcomes. In TMG, due to wide confidence interval ranges a conclusion of equivalence could be made only for recurrence of hyperthyroidism (mean -3.2%, 95% CI, -13.8 to +7.5%). A simplified dosage method for 131I treatment of hyperthyroidism, which omits 131I uptake adjustment, may improve procedure efficiency and patient convenience, and leads to an equivalent outcome in GD and probable equivalent outcome in TMG.

Effective management for hypothyroidism has been available for a century, thanks to the pioneering efforts of George Murray, who first tested injection of thyroid gland extracts in Newcastle. Radioiodine for the diagnosis and then treatment of Graves' hyperthyroidism was introduced by Hertz and Roberts in Boston, and by Leblond in Paris, in 1943, the same year that Astwood in the USA began to use the predecessors of modern antithyroid drugs. Despite this lengthy history, debate continues as to the most effective management of these common disorders. More use of radioiodine, including its use in euthyroid goitre, is being advocated as its safety is now well established. Recent developments in optimising these treatments will be considered in this brief review.

Unlabelled: The definitive treatment of hyperthyroidism in Europe is quite different from that in the United States. In Europe, the surgical approach is often preferred and considered safer than radioiodine treatment. European doctors usually prefer to surgically remove the thyroid and perform a pathologic examination of it. They consider it to be an essential diagnostic tool to identify possible diseases that might be associated with hyperthyroidism and even to detect the rare thyroid tumors that might be associated with thyroid hyperfunction. The aim of this study was to evaluate whether radioiodine therapy could be a risk factor for the misdiagnosis of thyroid cancer., Methods: We performed a retrospective revision of data we collected from 6647 patients (1171 [17.5%] men, 5476 [82.5%] women), all of whom underwent 1311 therapy for hyperthyroidism from 1970 to 1997. Of the whole group, 6.5% were younger than 40 y, 33.5% were 40-60 y old, and 60% were older than 60 y. Moreover, 5061 (76%) patients had either an autonomously functioning node or a toxic multinodular goiter. The other 1586 (24%) patients had Graves' disease., Results: After treatment, thyroid cancer was discovered in 10 (0.15%) patients, none of whom belonged to the group of patients with Graves' disease. Five of these patients were treated during a period from 1970 to 1980, when sonography was not routinely available. The incidence of thyroid cancer in the series of radioiodine-treated patients (150/100,000 over a 27-y period) was not significantly different from its incidence in the general population. The expected rate is 124.88 per 100,000 over a 27-y period., Conclusion: An accurate preliminary evaluation (clinical examination, sonography, and cytologic evaluation of fine-needle aspiration) is fundamental for a proper choice between radioiodine and surgical therapy.

The aim of the study was to evaluate differences in the use of radioactive iodine in the treatment of benign thyroid disease in Denmark. A questionnaire was distributed to all departments in Denmark which administer radioiodine in the treatment of benign thyroid disease (n = 20). Radioiodine is used for patients with toxic nodular goitre and for patients with relapse of toxic diffuse goitre. Four departments did not use radioiodine for volume reduction in non-toxic goitre. Patient informations included very different recommendations regarding cautions in relation to radioiodine treatment. Radioiodine is widely used in the treatment of benign thyroid disease. We recommend a national standardization of the cautions in relation to radioiodine treatment.

The radiolabeled glucose analogue F-18-Fluoro-Deoxyglucose (F-18-FDG) and Positron Emission Tomography (PET) were used to measure glucose metabolism of the thyroid in vivo. We evaluated patients with autonomous goitre before therapy with radioiodine in comparison to patients with normal thyroids. 30 patients with autonomous goitre underwent scanning the day before radioiodine therapy. 19 patients with head or brain tumours and normal thyroids were the controls. Overall F-18-FDG uptake was determined for all thyroids and proved to be significantly higher in autonomy patients compared to controls and in disseminated autonomous goitre slightly but not significantly higher than in focal autonomy. In autonomy patients F-18-FDG uptake increased with increasing radioiodine uptake and shorter radioiodine half-life. These results indicate that glucose metabolism is enhanced in the thyroids of patients with focal and disseminated autonomy. The negative correlation of radioiodine half-life and glucose metabolism as well as the positive correlation of radioiodine uptake and glucose metabolism suggest connections of glucose metabolism and iodine-dependent hormone synthesis in thyroid cells.

For more than 50 years, 131I has been recognized as an effective tool for controlling thyroid hyperplasia and hyperactivity. The fixed dose administration is the simplest method with doses of 111-370 MBq (3 to 10 mCi) 131I being administered. More sophisticated methods aiming to deliver a well-defined amount of 131I per gram of thyroid tissue are handicapped by problems related to the evaluation of the goiter size and the prediction of the sensitivity of thyroid cells to radiation. The use of 131I in nontoxic multinodular goiter is to be reserved for specific situations.

Some patients with very large goiters (>150 mL) are not candidates for surgery. We evaluated the feasibility of high dose 131I in such patients. Twenty-three patients (2 men and 21 women; median age, 67 yr; range, 42-86 yr) with very large goiter (8 toxic) were treated with calculated high dose 131I [median, 2281 megabecquerels (61.6 mCi); range, 988-4620 megabecquerels (26.7-124.9 mCi)]. During the 12-month observation period, goiter reduction and tracheal anatomy were monitored by magnetic resonance imaging, and the respiratory capacity was monitored by pulmonary function tests. Five patients (22%) developed hypothyroidism. Thyroid volumes were at baseline, after 1 week, and after 1 yr [mean +/- SEM, 311 +/- 28, 314 +/- 26 (P = NS), and 215 +/- 26 (P < 0.01) mL]. The relative changes 1 week after therapy ranged from -14.1% to 15.3%. After 1 yr the mean size was reduced by 33.9% (range, 13.5-61.4%). Only the initial goiter size showed a significant negative correlation to the percent reduction. The smallest cross-sectional area of the trachea decreased 9.2% within 1 week after treatment, but eventually emerged with a 17.9% larger area [mean +/- SEM, 84.3 +/- 4.8, 75.5 +/- 5.1 (P < 0.01), and 98.2 +/- 6.0 (P < 0.01) mm2]. The inspiratory parameter, FIF50%, improved after an initial insignificant decline [baseline therapy, after 1 week, after 3 months, and after 1 yr (mean +/- SEM), 2.37 +/- 0.24, 2.20 +/- 0.21 (P = NS), 2.51 +/- 0.23 (P = NS), and 2.76 +/- 0.25 (P = 0.01) L/s]. FIF50% correlated significantly with the smallest cross-sectional tracheal area (baseline, 1 week, and 1 yr: r = 0.74; P < 0.001, r = 0.63; P < 0.005, and r = 0.46; P < 0.05). Changes in tracheal anatomy did not correlate with changes in either lung dynamics or goiter size. In conclusion, very large goiters can be reduced by a third, on the average, with high dose 131I therapy without any initial clinically significant tracheal compression. Tracheal cross-sectional area as well as pulmonary inspiratory capacity improve. No serious adverse effects are seen.