Determination of the optimal minimum radioiodine dose in patients with Graves' disease: a clinical outcome study.

The study was performed under the auspices of the International Atomic Energy Commission, Vienna, Austria, with the aim of determining the optimal minimum therapeutic dose of iodine-131 for Graves' disease. The study was designed as a single-blinded randomised prospective outcome trial. Fifty-eight patients were enrolled, consisting of 50 females and 8 males aged from 17 to 75 years. Each patient was investigated by clinical assessment, biochemical and immunological assessment, thyroid ultrasound, technetium-99m thyroid scintigraphy and 24-h thyroid 131I uptake. Patients were then randomised into two treatment groups, one receiving 60 Gy and the other receiving 90 Gy thyroid tissue absorbed dose of radioiodine. The end-point markers were clinical and biochemical response to treatment. The median follow-up period was 37.5 months (range, 24-48 months). Among the 57 patients who completed final follow-up, a euthyroid state was achieved in 26 patients (46%), 27 patients (47%) were rendered hypothyroid and four patients (7%) remained hyperthyroid. Thirty-four patients (60%) remained hyperthyroid at 6 months after the initial radioiodine dose (median dose 126 MBq), and a total of 21 patients required additional radioiodine therapy (median total dose 640 MBq; range 370-1,485 MBq). At 6-month follow-up, of the 29 patients who received a thyroid tissue dose of 90 Gy, 17 (59%) remained hyperthyroid. By comparison, of the 28 patients who received a thyroid tissue dose of 60 Gy, 17 (61%) remained hyperthyroid. No significant difference in treatment response was found (P=0.881). At 6 months, five patients in the 90-Gy group were hypothyroid, compared to two patients in the 60-Gy group (P=0.246). Overall at 6 months, non-responders to low-dose therapy had a significantly larger thyroid gland mass (respective means: 35.9 ml vs 21.9 ml) and significantly higher levels of serum thyroglobulin (respective means: 597.6 microg/l vs 96.9 microg/l). Where low-dose radioiodine treatment of Graves' disease is considered, a dose of 60 Gy will yield a 39% response rate at 6 months while minimising early hypothyroidism. No significant advantage in response rate is gained by using a dose of 90 Gy. For more rapid therapeutic effect at the expense of an increased rate of hypothyroidism, doses in excess of 120 Gy may be required. Ultrasound determination of thyroid mass and measurement of serum thyroglobulin levels may be predictive of those patients who will be less responsive to low-dose therapy.     

Determination of the optimal minimum radioiodine dose in patients with Graves' disease: a clinical outcome study

The study was performed under the auspices of the International Atomic Energy Commission, Vienna, Austria, with the aim of determining the optimal minimum therapeutic dose of iodine-131 for Graves' disease. The study was designed as a single-blinded randomised prospective outcome trial. Fifty-eight patients were enrolled, consisting of 50 females and 8 males aged from 17 to 75 years. Each patient was investigated by clinical assessment, biochemical and immunological assessment, thyroid ultrasound, technetium-99m thyroid scintigraphy and 24-h thyroid ¹³¹I uptake. Patients were then randomised into two treatment groups, one receiving 60 Gy and the other receiving 90 Gy thyroid tissue absorbed dose of radioiodine. The end-point markers were clinical and biochemical response to treatment. The median follow-up period was 37.5 months (range, 24-48 months). Among the 57 patients who completed final follow-up, a euthyroid state was achieved in 26 patients (46%), 27 patients (47%) were rendered hypothyroid and four patients (7%) remained hyperthyroid. Thirty-four patients (60%) remained hyperthyroid at 6 months after the initial radioiodine dose (median dose 126 MBq), and a total of 21 patients required additional radioiodine therapy (median total dose 640 MBq; range 370-1,485 MBq). At 6-month follow-up, of the 29 patients who received a thyroid tissue dose of 90 Gy, 17 (59%) remained hyperthyroid. By comparison, of the 28 patients who received a thyroid tissue dose of 60 Gy, 17 (61%) remained hyperthyroid. No significant difference in treatment response was found (P=0.881). At 6 months, five patients in the 90-Gy group were hypothyroid, compared to two patients in the 60-Gy group (P=0.246). Overall at 6 months, non-responders to low-dose therapy had a significantly larger thyroid gland mass (respective means: 35.9 ml vs 21.9 ml) and significantly higher levels of serum thyroglobulin (respective means: 597.6 µg/l vs 96.9 µg/l). Where low-dose radioiodine treatment of Graves' disease is considered, a dose of 60 Gy will yield a 39% response rate at 6 months while minimising early hypothyroidism. No significant advantage in response rate is gained by using a dose of 90 Gy. For more rapid therapeutic effect at the expense of an increased rate of hypothyroidism, doses in excess of 120 Gy may be required. Ultrasound determination of thyroid mass and measurement of serum thyroglobulin levels may be predictive of those patients who will be less responsive to low-dose therapy.     

Long-term follow-up study of I-131 therapy for Graves' disease--index associated with late-onset hypothyroidism

We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.     

The outcome of treatment with adjusted dose of 131I to thyroid weight for Graves' disease by estimation of effective half life using a single radioiodine uptake measurement

In the determination of therapeutic 131I doses, it takes several days to measure effective half life (EHL) of radioiodine in thyroid glands (Ordinary method). We suggested the new method to estimate EHL by a single radioiodine uptake measurement (INDEX method). We evaluated the outcome of 131I treatment with these two methods in outpatients with Graves' disease. Eighty outpatients were treated with INDEX method (Group I) and 108 outpatients with Ordinary method (Group O). At the 5-yr follow up, the incidence of hypothyroidism in Group I was 22.5%, subclinical hypothyroidism 8.8%, euthyroidism 30.0%, subclinical hyperthyroidism 13.7% and hyperthyroidism 25.0%. In Group O, 17.6% of the patients were hypothyroid, 16.7% subclinical hypothyroid, 30.5% euthyroid, 9.3% subclinical hyperthyroid and 25.9% hyperthyroid. There were no significant differences between these two methods. We conclude that INDEX method surpasses Ordinary method in timesaver and is equal in effectiveness.     

Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.     

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.     

Effect of radioiodine therapy on thyroid nodule size and function in patients with toxic adenomas

BACKGROUND: Autonomously functioning toxic adenomas are a common cause of hyperthyroidism. Although 131I seems to be a good therapeutic option with little postablative hypothyroidism for these patients, only a small number of recent studies have objectively evaluated changes in nodule size by ultrasonography following radioiodine therapy. METHODS: We prospectively followed 39 patients with a mean age of 51.2 (35-75) years for 12 months and the patients who remained toxic thereafter, until euthyroidism was provided. Thyroid function tests, sonographic volumes were determined initially and 3, 6 and 12 months after treatment. Radioiodine doses of 3.7 MBq.g(-1) thyroid tissue corrected to a 100% 24 h 131I uptake were given. Thirty patients received a single dose, two required two doses and three required three to five doses of 131I due to persistent thyrotoxicosis. Sonographic volumes of the diffuse parts of the glands decreased significantly by 18% from a mean+/-SD value of 50+/-27.6 ml to 41+/-27.4 ml by the end of the 12 months. A significant decrease (8.3%, P=0.002) was achieved in the first three months. Toxic adenomas decreased in size more efficiently (54%) from a mean of 26+/-24 ml to 12+/-10 ml during 12 months, but also most significantly (28.8%, P=0.003) in the first 3 months of the follow-up. Thirty of the patients (76.9%) became euthyroid at the end of 12 months of follow-up. Four patients (10.3%) became overtly hypothyroid during the follow-up. CONCLUSION: Single or multiple doses of radioiodine can successfully treat toxic adenomas with a low rate of hypothyroidism and considerable nodule-volume reduction.     

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.     

Single dose planning for radioiodine-131 therapy of Graves’ disease

Objective  Patients with Graves’ disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used.Methods: Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. Results  No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. Conclusions  No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed.     

Comparative evaluation of two fixed doses of 185 and 370 MBq 131I, for the treatment of Graves' disease resistant to antithyroid drugs

Radioiodine (131I) treatment is often applied for the treatment of Graves' disease (GD). The optimal dose of 131I for Graves' hyperthyroidism is debated. Various techniques suggest either fixed doses or varying doses based on elaborate calculations of the gland size, 131I uptake, and 131I turnover. Fixed dose regimens avoid dose calculations but there is no consensus on the actual dose to be administered. We compared two routinely recommended fixed 131I doses of 185 and 370 MBq for this purpose. Fifty nine patients with GD who had not been previously treated with 131I were randomized in two groups. Group A consisted of 33 patients who were treated with 185 MBq of 131I. Group B consisted of 26 patients who were treated with 370 MBq of 131I. Group A patients were 21% male and 78% female, mean age 38.1+/-14.4, range 15 to 77 y. Group B patients were 27% male and 73% female, mean age 40.7+/-11.7, range 27 to 72 y. All patients were reexamined every six months for two years. The following clinical outcomes were noticed: a) Persistent hyperthyroidism, which was considered as failure to treatment, requiring further 131I treatment. b) Hypothyroidism; requiring life-long replacement treatment. c) Euthyroid state. Euthyroid and hypothyroid states were considered as a response to treatment of hyperthyroidism. In Group A, 10 patients (30.3%) became euthyroid and 6 (18.2%) hypothyroid (an overall response of 48.5%), while 17 (51.5%) remained hyperthyroid by the end of the follow-up period. In Group B, 10 patients (38%) became euthyroid and 13 (50%) hypothyroid, an overall response of 88.5%. Non responders were 3 patients (11.5%). No correlation was noted between the outcome of treatment and age, sex, size of the thyroid gland or thyroid uptake in each Group of patients, while a significant correlation was noted between the disease outcome and the amount of administered 131I (P<0.003). The incidence of hypothyroidism by the end of two years of follow up was less in Group A than in Group B and the incidence of non responders to treatment was lower in Group A. In view of the higher cost of treatment, the longer time elapsing to treatment, the number of office visits by the patients and the higher number of patients with persistent hyperthyroidism in Group A, we conclude that a fixed dose of 131I of 370 MBq is more useful and effective for the treatment of GD as compared to 185 MBq of 131I.     

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.     

Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma

Iodine kinetics were studied in patients with differentiated thyroid cancer while euthyroid under exogenous thyroid stimulating hormone (TSH) and while hypothyroid to detect differences in radioiodine uptake, distribution and elimination. Nine patients with total or near-total thyroidectomy on thyroid hormone suppressive therapy received two or three daily doses of 0.9 mg recombinant human TSH (rhTSH) followed by administration of a diagnostic activity of 2 mCi (74 MBq) iodine-131. After the biokinetics assessments had been performed, patients stopped taking thyroid hormones to become hypothyroid. A second 2 mCi (74 MBq) diagnostic activity of ¹³¹I was administered, followed by a second set of biokinetics assessments. One week later the patients underwent remnant ablation with a therapeutic activity of ¹³¹I. A comparison of the ¹³¹I kinetics in the patients while euthyroid and while hypothyroid showed major differences in the doses to the remnant as well as in residence times and radiation exposure to the blood. In the first diagnostic assessment the remnant dose was higher in eight of the nine patients and clearance of the activity from the blood was faster in all of them. The data from this study suggest that radioiodine administration is potent and safe when administered to euthyroid patients following rhTSH administration. Enhanced residence time in the remnant and decreased radiation exposure to the blood were noted when patients were euthyroid compared to when they were rendered hypothyroid. However, all patients received diagnostic activities in the same order: first while euthyroid, followed by hypothyroidism. It is quite possible that "stunning" from the radioiodine administered in the initial uptake study inhibited the subsequent uptake of radioiodine by the remnant lesions in the second uptake study.     

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.     

Hyperthyroidism with metastatic follicular thyroid carcinoma

A 70-yr-old woman presented with hyperthyroidism and metastatic follicular carcinoma of the thyroid. The blood level of thyroid stimulating immunoglobulin (TSIg) was elevated. A total thyroidectomy was performed. One month later she remained hyperthyroid. Three weeks after therapy with 218 mCi of I-131 sodium iodide, the patient was euthyroid. Six months after the initial radioiodide therapy, she was again hyperthyroid and was given a second oral treatment dose of I-131 (220 mCi). Five months later, the patient had again become euthyroid. It is likely that initially the woman's metastases were producing sufficient hormone to render her hyperthyroid. After thyroidectomy and two large doses of radioiodide, she has remained euthyroid without having to take exogenous hormone. The blood level of TSIg had become undetectable. Based on this finding, we offer a tentative classification of the causes of hyperthyroidism in patients with thyroid carcinoma.     

Radioiodine therapy for Plummer's disease based on the thyroid uptake of technetium-99m pertechnetate

The aim of this retrospective study was the evaluation of a TcTUs (global technetium-99m pertechnetate thyroid uptake under suppression)-based approach in 370 patients with thyroid autonomy (Plummer's disease) treated by radioiodine therapy (RIT) under standardised conditions. The analysis included 370 patients (309 females, 61 males; mean age 64+/-11.6 years) treated for thyroid autonomy [unifocal (UFA), 36.8%; multifocal (MFA), 55.7%; disseminated (DISA), 7.6%]. During RIT all patients were under thyroid suppression (TSH< 0.1 microU/ml) and without thionamide treatment. Of the 370 patients, 73% (n=271) were manifestly hyperthyroid and 27% (n=99) subclinically hyperthyroid. A dosimetric study included uptake measurements 24, 48, and 96 h p.i. For dose estimation the Marinelli algorithm was used. For retrospective definition of the target volume we used the equation: Autonomous volume = TcTUs x 5. The spectrum of doses given in our patients ranged from 81 to 1933 Gy. After 18 months of follow-up, RIT was successful (TSH>0.5 microqU/l and/or TcTUs<1.6%) in 310 patients (84%). Of these patients, 291 (94%) were euthyroid (with or without L-thyroxine) and 19 (6%) subclinically hypothyroid (TSH>4 microU/ml). A dose of 350-450 Gy to the autonomous tissue resulted in a success rate of 97% in the UFA group and 81% in the MFA/DISA group. Decrease in total thyroid volume and TcTUs did not differ significantly between successfully treated patients and patients with persistent autonomy. Multivariate analysis of all 370 patients identified four independent factors that negatively influenced the therapeutic success: high pretherapeutic thyroid volume (P=0.0001; odds ratio: 1.017), high pretherapeutic TcTUs values (P=0.0001; odds ratio: 1.378), multifocal/disseminated autonomy (P=0.0056; odds ratio: 3.245) and low target dose (P=0.017; odds ratio: 0.997). It is concluded that the high success rate in the treatment of UFA indicates the concept of TcTUs-based RIT to be valid, but that in the therapy of MFA/DISA the target dose has to be corrected if the total thyroid volume exceeds a critical threshold.     

Management of patients with thyroid carcinoma: application of thallium-201 scintigraphy and magnetic resonance imaging

Thyroid carcinoma has the ability to concentrate radioiodine, an attribute that can be used both for detection of thyroid cells and for treatment. Unfortunately, however, radioiodine uptake is not observed in all patients and a radioiodine scan requires that the patient be rendered hypothyroid for 4-6 wk. In the present study, we analyzed the utility of thallium-201 scanning and the usefulness of magnetic resonance imaging (MRI) in the detection of thyroid cancer. Nineteen patients with thyroid cancer had a total of 24 radioiodine scans, 33 thallium scans, and 10 MRI examinations. Of the 19 patients in the study, 17 had differentiated thyroid carcinoma. In these 17 cases, all paired studies were concordant for the presence (n = 7) or absence (n = 10) of disease. However, in one case (Patient 10), the 201Tl studies showed far more extensive disease than was observed on the 131I scan. Thyroid cancer was also detected on seven MRI studies. In summary, thallium and MRI scans are adjunctive techniques to radioiodine scanning that can either confirm the presence of neck bed activity, residual disease or metastatic cancer and may delineate tumor deposits not detected by radioiodine scanning. Thallium may be capable of detecting tumor deposits even while a patient remains euthyroid.     

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.     

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 treatment of solitary functioning thyroid nodules

Forty-eight patients with hyperthyroidism due to a single toxic nodule have been treated with radioiodine (131I). The mean follow-up period is 37 months. All patients were rendered euthyroid and no cases of hyperthyroidism have been observed. Forty patients required only one dose of 131I to render them euthyroid, six patients required more than one dose and two patients initially rendered euthyroid relapsed during follow-up and required further 131I treatment. It is concluded that a single fixed dose of 131I is a simple, effective treatment for a solitary toxic thyroid nodule and does not cause hypothyroidism.     

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 (131I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule. The risk of development of hypothyroidism is low if extranodular uptake of 131I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.