In vivo and in vitro studies into the immunological changes following iodine 131 therapy for Graves' disease.

Radio-iodine therapy for Graves' disease is followed by immunological changes in addition to effects on thyroid hormone production. The present study examined these changes and the mechanisms responsible for them. Of the 15 patients enrolled in the study, 10 became hypothyroid in the first year after iodine 131 therapy. Patients who became hypothyroid had a tendency to show a rise in serum thyrotropin receptor antibody levels (30 +/- 14 to 40 +/- 9 units; NS) and a significant rise in immunoglobulin production (324 +/- 153 to 740 +/- 200 ng/ml; P less than 0.0005) from mitogen-stimulated peripheral blood lymphocytes (a measure of B-cell activity) 2 months after iodine 131 therapy. The increases were not seen in the patients who remained euthyroid at 1 year. In vitro studies suggested that the rise in B-cell activity is due to a fall in suppressor T cell numbers, a change shown to occur following iodine 131 therapy in previous studies. Our results indicate that immunological changes do arise after iodine 131 therapy for Graves' disease but appear to be confined to patients who subsequently became hypothyroid. It is not possible from this study to determine whether the immunological changes appear as a consequence of thyroidal destruction leading to hypothyroidism or whether they contribute directly to it.     

Early prediction of hypotheroidism following 131I treatment for Graves' disease

The aim of this study was twofold. Firstly to assess the post treatment predictive value of various biochemical and immunological tests for early hypothyroidism after ¹³¹I therapy for Graves' disease, and secondly to determine whether or not pretreatment with Carbimazole protects against post treatment hypothyroidism. The early changes observed in serum T₃, T₄, TSH, thyroid microsomal and thyroglobulin antibody levels were found to be of no predictive value. A sharp rise, around 2 months, in TRAb levels following ¹³¹I therapy indicated that hypothyroidism was likely to occur. This rise was thought to reflect a greater degree of thyroid damage. Lower levels of thyroglobulin in patients who had become hypothyroid by 12 months after treatment would support this view. Five weeks Carbimazole pretreatment in this relatively small group of patients did not appear to protect against hypothyroidism.     

Early prediction of hypothyroidism following 131I treatment for Graves' disease

The aim of this study was twofold. Firstly to assess the post treatment predictive value of various biochemical and immunological tests for early hypothyroidism after 131I therapy for Graves' disease, and secondly to determine whether or not pretreatment with Carbimazole protects against post treatment hypothyroidism. The early changes observed in serum T3, T4, TSH, thyroid microsomal and thyroglobulin antibody levels were found to be of no predictive value. A sharp rise, around 2 months, in TRAb levels following 131I therapy indicated that hypothyroidism was likely to occur. This rise was thought to reflect a greater degree of thyroid damage. Lower levels of thyroglobulin in patients who had become hypothyroid by 12 months after treatment would support this view. Five weeks Carbimazole pretreatment in this relatively small group of patients did not appear to protect against hypothyroidism.     

Discriminant factors affecting early outcome of radioiodine treatment for Graves' disease

Pretreatment clinical, biochemical, iodine-131 (131I) scan and tracer-kinetic parameters were studied in 827 Chinese patients with Graves' disease treated with radioactive iodine. One year after 131I therapy, 56.7% were euthyroid, 33.9% were still thyrotoxic and 9.4% were hypothyroid. Discriminant analysis of all pretreatment variables identified thyroid mass, presenting free thyroxine index and 4 h 131I uptake as the three variables most helpful in discriminating the early outcome group of 131I therapy. The findings suggest that patients with large goitres and severe disease may require higher doses of 131I for treatment of Graves' disease.     

Long-term carbimazole intake does not affect success rate of radioactive 131Iodine in treatment of Graves' hyperthyroidism

OBJECTIVE: The aim of this study is to assess the effect of long-term antithyroid drug intake on the success rate of iodine-131 (131I) treatment of Graves' hyperthyroidism, and to explore other clinical/laboratory factors that may predict/affect the treatment outcome. MATERIALS AND METHODS: Fifty-eight patients with Graves' disease were referred for radioactive iodine therapy after failure of medical treatment, which was given for at least 6 months. Antithyroid drug (carbimazole) was stopped for at least 2 days before administration of a fixed dose of 370 MBq. Treatment outcome was determined at the end of 1-year follow-up after iodine administration. Treatment success was reported if the thyroid hormonal profile indicated euthyroid or hypothyroid state. RESULTS: One year after 131I administration, 19% of our patients were still hyperthyroid (treatment failure), 15.5% became euthyroid and 65.5% were hypothyroid (treatment success, 81%). No statistically significant correlation was found between treatment outcome and patient's age at the time of I administration (P=0.20); duration of medical treatment before 131I administration (P=0.22) and duration of stoppage of medical treatment before 131I intake (P=0.15). In contrast, there was significant association between treatment outcome and pretreatment Tc99m-thyroid uptake (P=0.0001), thyroid size (P=0.001) and TSH level (P=0.04). Using receiver operator characteristic curve analysis, we generated a cut-off value for thyroid uptake (18%) and thyroid weight (70 g) to predict response to 370 MBq of 131I. The 18% thyroid uptake cut-off value predicted treatment outcome with 93.6% sensitivity, 100% specificity and 94.8% accuracy, whereas the 70 g thyroid weight predicted treatment outcome with sensitivity, specificity and accuracy of 80.9, 72.7 and 79.3%, respectively. CONCLUSION: Long-term carbimazole treatment will not increase the failure rate of 131I treatment in patients with Graves' disease if the drug was discontinued for at least 2 days before iodine administration. A fixed dose of 370 MBq is efficient in patients with Tc99m-pertechnetate thyroid uptake less than 18% and gland weight less than 70 g. Patients with larger goitres and/or higher thyroid uptake level will probably need a higher dose of radioactive iodine.     

Three basic patterns of changes in serum thyroid hormone levels in Graves’ disease during the one-year period after radioiodine therapy

The purpose of this study was to clarify the characteristic patterns of the thyroid hormonal changes in Graves' disease during the one-year period after 131I therapy considering that few serial hormonal data during this period are available in the literature. METHODS: The levels of serum T3, T4 and FT4 before and during one year were plotted as a function of time in 70 therapy courses of 58 patients without subsequent antithyroid or steroid therapy. RESULTS: 35 euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year after therapy. Although individual patients had individual hormonal changing patterns, 3 common basic patterns were observed from baseline to one month (early) and thereafter (late), respectively. The early patterns were a decrease in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late patterns were a stable state after an initial decrease with a bottom followed by an increase (valley pattern) in 47 (67%), a stable state after an initial increase with a peak followed by a decrease with a bottom and a subsequent re-increase (mountain pattern) in 12 (17%) and a late stable state after a gradual slow decrease without an obvious bottom near or till one year (downhill pattern) in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of 57 with the valley or mountain pattern. Most of the bottom levels (81%) and transient abnormal changes including transient hypothyroidism (93%, 13/14), peak or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6 months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months, in 18% (12/68) from 6 to 9 months and in 25% (17/68) thereafter. CONCLUSION: Although the changes in thyroid hormones are not constant in Graves' disease during one year after 131I therapy, there are three basic patterns; valley, mountain and downhill patterns from one month after therapy. The post-therapeutic stable state can be judged by the hormonal level recovered from the bottom in most patients.     

Radioiodine therapy for Graves' disease: multivariate analysis of pretreatment parameters and early outcome

Twenty-one clinical, biochemical, scan and tracer-kinetic parameters were documented in 76 patients with Graves' disease who had received a standard 5-mCi therapy dose of 131I. Linear discriminant analysis was then undertaken to determine what combination of variables best predicted outcome. One year after therapy, 40 patients were euthyroid, 11 were hypothyroid, and 25 were still thyrotoxic. Linear discriminate functions combining 24-h 131I uptake, the presence or absence of thyroid eye signs and a computer-derived measurement of thyroid cell mass best discriminated the three outcome groups. The proportion of patients correctly reclassified according to outcome using these functions was, however, only just over 50%. It is concluded that no single or combination of pretreatment variables predicts early outcome with sufficient confidence to justify a rigorously 'scientific' approach to the administration of 131I therapy for Graves' disease.     

Airway complication occurring during radioiodine treatment for Graves' disease

Airway complications rarely occur in ¹³¹I radioiodine therapy for Graves' disease. This study presents two cases in which ¹³¹I therapy caused this acute complication. The patients complained of the symptom 6 h and 33 h after administration of ¹³¹I. A histamine H1 receptor antagonist and hydrocortisone rapidly resolved symptoms in both cases. These two cases remind physicians that ¹³¹I therapy for Graves' disease may cause potentially life-threatening complications.     

Long-term follow-up studies on Iodine-131 treatment of hyperthyroid graves’ disease based on the measurement of thyroid volume by ultrasonography

In the present series of studies, the long-term (four year) effect of 80 Gy of¹³¹I treatment was evaluated in patients with hyperthyroid Graves’ disease whose thyroid volumes have been accurately estimated with a high resolution ultrasound scanner. One year after¹³¹I treatment, 23.1 % (3 out of 13 patients) remained hyperthyroid, 69.2% (9 out of 13) became euthyroid, and 7.7% (1 out of 13) were in a hypothyroid state. Since three patients in a hyperthyroid state one year after treatment were subsequently treated with either antithyroid drugs or additional¹³¹I treatment, the remaining ten patients (9 euthyroid and 1 hypothyroid patients) have been followed up for three more years. Two patients developed a hypothyroid state three years after treatment and one patient four years after treatment. Overall, 60% (6 out of 10 patients) were in a euthyroid state and 40% (4 out of 10) in a hypothyroid state, four years after 80 Gy¹³¹I treatment. There was no significant difference between eu- and hypothyroid groups in the sex ratio, age, radiation dose, therapeutic dose, thyroid gland volume, 24-hr¹³¹I uptake, the effective half-life of¹³¹I in the thyroid or the duration of hyperthyroidism. In our preliminary studies, the incidence of late hypothyroidism in our¹³¹I treatment is similar to those previously reported. These suggest that uncertain factor(s), such as inhomogeneity of iodine distribution in the thyroid, unequal sensitivity of the thyroid cells to the radiation, and/or persistent destructive effects of the autoimmune process may influence the long-term effect of¹³¹I treatment of Graves’ disease.     

Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations

Seventy female patients who had been treated with high doses of iodine-131 for differentiated thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The total ¹³¹I dose ranged from 1.85 to 16.55 GBq (mean±SD=4.39±25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean±SD = 24.3±5.0 years) and the interval from ¹³¹I therapy topregnancy varied from 2to 10 years (mean±SD = 5.3±2.8 years). The estimated radiation doseto the gonads ranged from 10 to 63 cGy (mean±SD = 24.0±13.5 eGy). All patients were treated with l-thyroxine at doses capable of suppressing thyroid-stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallot's trilogy and three had a low birth weight though with subsequent normal growth; the others were healthy with subsequent normal growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high ¹³¹I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after ¹³¹I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion.     

Radioiodine therapy for Graves' disease: multivariate analysis of pretreatment parameters and early outcome

Twenty-one clinical, biochemical, scan and tracerkinetic parameters were documented in 76 patients with Graves' disease who had received a standard 5-mCi therapy dose of ¹³¹I. Linear discriminant analysis was then undertaken to determine what combination of variables best predicted outcome. One year after therapy, 40 patients were euthyroid, 11 were hypothyroid, and 25 were still thyrotoxic. Linear discriminate functions combining 24-h ¹³¹I uptake, the presence or absence of thyroid eye signs and a computer-derived measurement of thyroid cell mass best discriminated the three outcome groups. The proportion of patients correctly reclassified according to outcome using these functions was, however, only just over 50%. It is concluded that no single or combination of pretreatment variables predicts early outcome with sufficient confidence to justify a rigorously scientific approach to the administration of ¹³¹I therapy for Graves' disease.     

Dose-response study on thyrotoxic patients undergoing positron emission tomography and radioiodine therapy

With the acknowledged problems associated with assessment of functioning thyroid mass and hence radiation dose, our policy had been to give 75 MBq iodine-131 at 6-monthly intervals to patients with Graves' disease until they became euthyroid. Since positron emission tomography (PET) has been available at this hospital, the radiation dose to the thyroid has been calculated with an accuracy of 20%, the thyroid mass being determined from an iodine-124 PET scan. A dose-response study has been carried out on 65 patients who have received single or cumulative radiation doses of <80 Gy. The results show that patients who receive a low radiation dose (<20 Gy) at their first treatment have a high probability of remaining toxic at 12 months. In contrast, patients who receive higher radiation doses (>40 Gy) at their first treatment have a high probability of control. The probability of becoming euthyroid increases more rapidly with increasing radiation dose than the probability of becoming hypothyroid. Following this dose-response study, a new treatment protocol has been introduced. A ¹²⁴I PET tracer study prior to ¹³¹I therapy will be performed to enable a prescribed thyroid dose of 50 Gy to be delivered to patients with Graves' disease. Further ¹³¹I therapy will only be considered if patients are still toxic at 12 months.     

Renal excretion of iodine-131 labelledmeta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

Iodine-131 labelledmeta-iodobenzylguanidine ([¹³¹I]MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [¹³¹I]MIBG (3.1–7.5 GBq) to 17 patients (n=32 courses), aged 2–73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine att=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%–18% of [¹³¹I]meta-iodohippuric acid ([¹³¹I]MIHA), the cumulatively excreted radioactivity consisted of >85% [¹³¹I]MIBG, with 6% of the dose excreted as free [¹³¹I]iodide, 4% as [¹³¹I]MINA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [¹³¹I]MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [¹³¹I]meta-iodobenzoic acid in two patients, a possible metabolic pathway for [¹³¹I]MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity.     

Long-term results of two schedules of radioiodine treatment for toxic multinodular goitre

The long-term effects of two schedules of radioiodine therapy in patients with toxic multinodular goitre were evaluated. Forty-five patients (group A) were treated with low doses and 58 patients (group B) with calculated doses adjusted for thyroid weight (1.85–3.70 MBq/g) and radioactive iodine uptake. Follow-up (mean ± SEM) was 4.3 ± 0.2 years and 5.2 ± 0.3 years, respectively (P>0.1). At the end of follow-up, hyperthyroidism was successfully reversed in 73% (group A) and 88% (group B). In each group, hypothyroidism was present in 7%. The total dose per gram of thyroid tissue was not significantly different in groups A and B (2.1 ± 0.2 vs 2.7 ± 0.2 MBq/g). However, for patients treated with calculated doses the number of ¹³¹I administrations was significantly lower (1.3 ± 0.1) than for patients treated with low doses (2.2 ± 0.2), and the percentage of patients who were adequately treated with a single dose was more than twice as high (66% in group B versus 27% in group A). Euthyroidism was reached within a significantly shorter time after treatment with calculated doses (median time 0.6 years in group B vs 1.5 years in group A; life table analysis). It is concluded that radioiodine is an effective treatment for toxic multinodular goitre with a low risk of post-treatment hypothyroidism and that calculated (higher) doses appear to be preferable to low doses.     

What influences early hypothyroidism after radioiodine treatment for Graves' hyperthyroidism?

OBJECTIVE: The objective of this study was to evaluate the factors influencing the occurrence of early hypothyroidism after radioiodine treatment of Graves' hyperthyroidism. MATERIAL AND METHODS: Of 147 patients with Graves' disease (GD) treated with radioactive I-131 (RAI) in our thyroid clinic between July 2003 and December 2004, 84 were followed at 2 and 4 to 5 months after treatment. The age range was 12 to 75 years and the dosage range in these patients was 7.4 to 29.9 mCi. Twenty-four were males and 60 were females. Factors possibly contributing to post-RAI hypothyroidism are: dosage of I-131, age, gender, size of the gland, initial serum free T4, free T3, thyroid-stimulating hormone (TSH) levels, pretreatment with antithyroid drugs, radioactive iodine uptake, and duration of disease. RESULTS: All patients had low TSH, elevated FT4, and elevated radioactive iodine uptake (RAIU) at 4 and/or 24 hours. Of the 84 patients followed, 46% of the males and 62% of the females became hypothyroid at 4 to 5 months (57% of the total). Twenty-one patients remained hyperthyroid and 14 patients became euthyroid. Multivariate analysis of these 84 patients showed no statistically significant single contributing factor for the development of early hypothyroidism. CONCLUSION: The early onset of hypothyroidism after RAI in GD is very common (57%) and unpredictable. Thus, after RAI treatment, all patients must be closely monitored for the development of this disorder.     

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

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.     

Radioimmunotherapy using 131I-rituximab in patients with advanced stage B-cell non-Hodgkin’s lymphoma: initial experience

Purpose The aim of this study was to evaluate the safety, toxicity and therapeutic response of non-myeloablative radioimmunotherapy using ¹³¹I-rituximab in previously heavily treated patients with B-cell non-Hodgkins lymphoma (B-NHL).Methods Nine patients with relapsed, refractory or transformed B-NHL received ten radioimmunotherapies. Patients had a median of 5 (range 2–7) prior standard therapies. Four patients had received prior high-dose chemotherapy followed by autologous stem cell transplantation, and eight had received prior rituximab therapy. Histopathology consisted of four mantle cell, one follicular and four diffuse large B-cell lymphomas. Rituximab, a monoclonal chimeric anti-CD20 antibody (IDEC-C2B8), was labelled with ¹³¹I using the Iodogen method. The administered activity (2,200±600 MBq) was based on a dosimetrically calculated 45 cGy total-body radiation dose. All patients received an infusion of 2.5 mg/kg of rituximab prior to administration of the radiopharmaceutical.Results No acute adverse effects were observed after the administration of ¹³¹I-rituximab. Radioimmunotherapy was safe in our patient group and achieved one complete response ongoing at 14 months and two partial responses progressing at 12 and 13 months after treatment. One partial responder was re-treated with radioimmunotherapy and achieved an additional progression-free interval of 7 months. Four non-responders with bulky disease died 4.8±2.0 months after therapy. Three patients had an elevated serum lactate dehydrogenase (LDH) level prior to radioimmunotherapy and none of the patients responded. Of two patients who received radioimmunotherapy as an additional treatment after salvage chemotherapy, one continues to be disease-free at 9 months and one relapsed at 5 months follow-up. Reversible grade 3 or 4 haematological toxicity occurred in seven of nine patients. Median nadirs were 35 days for platelets, 44 days for leucocytes and 57 days for erythrocytes.Conclusion Radioimmunotherapy with ¹³¹I-rituximab in previously heavily treated B-NHL patients was safe and well tolerated, and four out of ten therapies induced responses. Radioimmunotherapy was less efficient in patients with bulky disease and elevated LDH. Severe haematological toxicity in seven patients did not cause significant clinical problems. Radioimmunotherapy seems to be an additional therapeutic option in carefully selected therapy-refractory B-NHL patients.     

Iodine-131 uptake and turnover rate vary over short intervals in Graves' disease

From a Dutch questionnaire, it was apparent that nearly all institutions used percentage of radioiodine uptake for calculation of the radioiodine dose in Graves' disease. Although there is a general belief that fluctuations in radioiodine uptake may occur, with few exceptions relatively long intervals were accepted between the uptake measurement and the actual therapy dose. With the aim of optimizing the pretherapeutic work-up, we evaluated the stability of iodine uptake over time in patients with Graves' disease who were referred for 131I therapy. 131I uptake was measured in 300 consecutive patients for the calculation of the required 131I therapy dose; data were complete for 291 patients (97%). After discontinuing thyroid medication for 3 days, standardized thyroid probe measurements were performed 5 and 24 h after ingestion of a capsule containing 0.37 MBq 131I-NaI. Measurements were performed at the time of scintigraphic diagnosis (test 1), as well as immediately before 131I therapy (test 2). The time interval between test 1 and test 2 ranged from 2 to 421 (median 40) days. A relative increase or decrease greater than 10% between tests 1 and 2 occurred in 180 of 291 cases (62%) at 5 h and in 158 of 291 patients (54%) at 24 h. These changes were not related to the interval between the tests or to initial uptake values, thyroid mass, gender or age. Rapid turnover of radioiodine (5 h/24 h uptake ratio > 1) was noted in 17% of the patients during test 1 and in 15% during test 2. Rapid turnover was persistent (present in both tests 1 and 2) in only 9%. We conclude that patients with Graves' disease show considerable changes in 131I uptake over relatively short periods of time, and the turnover rate of 131I in this condition is not constant.     

High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves' disease

BACKGROUND AND OBJECTIVE: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT. METHODS: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients. RESULTS: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9). CONCLUSIONS: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.     

Outpatient management of patients with large multinodular goitres treated with fractionated radioiodine

The efficacy of fractionated out-patient radioiodine therapy in 38 patients with compressive symptoms due to long-standing large multinodular goitres was assessed. The diagnosis was established by clinical assessment in addition to technetium-99m pertechnetate thyroid scan or computed tomography scan of the thyroid and mediastinum. Oral iodine-131 therapy was administered as a 2.22 GBq (60 mCi) cumulative dose over 4 months (555 MBq per month). All patients were monitored with serum thyroid-stimulating hormone and free thyroxine (± free tri-iodothyronine) assays before the treatment and after each dose fraction. Clinical and biochemical follow-up was performed on all patients and ranged from 6 to 45 months after therapy. The patients consisted of 35 female and three male patients with a median age of 59 years (range 37–87 years). Prior to treatment 20 patients were biochemically hyperthyroid and 18 were euthyroid. Overall, 71% of patients reported a subjective improvement in compressive symptoms and 29% reported no change. Clinically assessed reduction in goitre size occurred in 92% of patients while there was no change in 8%. At 3 months of follow-up, 31% of patients had become hypothyroid and at 18 months 66% were hypothyroid. Seven hyperthyroid patients (35%) became euthyroid and 13 hyperthyroid patients (65%) became hypothyroid. Three patients who became hypothyroid experienced neck soreness (transient in one patient, persistent in two patients). There were no differences in outcome between patients who were hyperthyroid and those who were euthyroid prior to treatment. Fractionated out-patient radioiodine therapy showed excellent short- and medium-term safety, was very well tolerated and offered a satisfactory alternative treatment to surgery. Received 23 May and in revised form 11 August 1997