Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves' disease

The treatment options for the hyperthyroidism of Graves disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of (131)I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of (131)I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs.     

High dose of (131)I therapy for the treatment of hyperthyroidism caused by Graves' disease

Radioactive iodine ((131)I) has become the most widely used therapy for patients with hyperthyroidism caused by Graves' disease in the United States. There remains, however, significant variability among (131)I dosing regimens, and it is clear that most patients ultimately develop hypothyroidism after therapy. To avoid persistent hyperthyroidism, we adopted a high dose (131)I therapy protocol based on measurement of 24-h thyroid (123)I uptake designed to deliver 8 mCi (296 MBq) to the thyroid gland 24 h after (131)I administration. To evaluate the efficacy of this protocol, we reviewed our clinical experience over a 7-yr period. We treated 261 patients (219 women and 42 men) with hyperthyroidism caused by Graves' disease with (131)I [mean dose, 14.6 mCi (540 MBq)] between 1993 and 1999. Before treatment, 207 (79%) had received an antithyroid drug (109 propylthiouracil and 98 methimazole). We determined their thyroid status 1 yr after treatment in relation to age, pretreatment with an antithyroid drug, pretreatment thyroid size, and dose of (131)I retained in the thyroid 24 h after treatment. Among the 261 patients, 225 (86%) were euthyroid or hypothyroid 1 yr after treatment, and 36 patients (14%) had persistent hyperthyroidism and required a second treatment. The patients who had persistent hyperthyroidism were younger (P < 0.01), had larger thyroid glands (P < 0.01), higher pretreatment thyroid (123)I uptake values (P < 0.01), and higher serum T(4) concentrations (P < 0.01) and were more likely to have taken antithyroid medication before administration of (131)I (P = 0.01). Five of these patients developed transient hypothyroidism, followed by thyrotoxicosis. There was an asymptotic, inverse relationship between the retained dose of (131)I at 24 h and persistent hyperthyroidism, revealing a 5-10% failure rate despite delivery of up to 400 microCi (14.8 MBq)/g. A dose of (131)I that results in accumulation of 8 mCi (296 MBq) in the thyroid gland 24 h after administration is an effective treatment for the majority of patients with Graves' hyperthyroidism. Young patients with larger thyroid glands, higher serum T(4) concentrations, and higher 24-h thyroid (123)I uptake values, and those pretreated with antithyroid medication for greater than 4 months are at higher risk for treatment failure. A higher dose of (131)I may be advisable in such patients.     

125I therapy in Graves' disease. Long-term results in 355 patients.

Because of the physical and radiobiologic differences between 125I and 131I, a trial using 125I to treat hyperthyroidism was undertaken in the hope of controlling hyperthyroidism without causing subsequent hypothyroidism. Three hundred fifty-five patients with diffuse toxic goitres were treated and have been under review for an average of 49.4 months: 63.4% are euthyroid, 33.5% are hypothyroid, and 3.1% remain hyperthyroid. Different groups of patients received a wide range of doses of 125I (4.0 to 56.0 mCi), and the lowest incidence of hypothyroidism (23%) was in the group that received between 6.0 and 10.5 mCi. Sixty-three percent of the patients whose initial dose was greater than 20.0 mCi are hypothyroid. Persistent hyperthyroidism was common in patients who received small doses. Because of the high incidence of posttreatment hypothyroidism in this series and because 131I has stood the test of time, we believe that 131I is the radionuclide of choice for the routine treatment of hyperthyroidism.     

Successful treatment of solitary toxic thyroid nodules with relatively low-dose iodine-131, with low prevalence of hypothyroidism

Forty-five patients with solitary toxic thyroid adenomas received 131I (mean dose, 10.3 mCi) for treatment of hyperthyroidism and were followed for 4.9 +/- 3.2 years (range, 0.5 to 13.5). Seventy-seven percent were euthyroid by 2 months, 91% by 6 months, and 93% by 1 year. Only 3 patients did not respond to a single dose of 131I, but all responded to multiple doses. Late recurrent hyperthyroidism occurred in 3 patients at 4.5, 6, and 10 years after treatment with a single dose of 131I. No patient developed clinical hypothyroidism, and none had a low serum thyroxine level associated with an elevated serum thyrotrophin level. Three patients developed minimal elevations in serum thyrotrophin levels: 1, 4, and 7.5 years after 131I treatment, their thyrotrophin levels were 8.4, 6.2, and 9.6 microU/mL, respectively. All 3 had normal serum thyroxine levels and were clinically euthyroid. Mean serum thyroxine concentrations of all patients were unchanged between 1 and more than 9 years of follow-up. These data suggest that solitary toxic adenomas may be treated with relatively low doses of 131I (5 to 15 mCi), and that post-treatment hypothyroidism is very unusual.     

Comparison of RA 131I treatment protocols for Graves' disease

The efficacy of 131I therapy in achieving euthyroidism has been studied in a group of 264 patients followed for up to 10 yr. One hundred and eighty-six were given a dose adjusted for thyroid size and radioactive iodine uptake (Protocol 1), and a second group received the same dosage followed by antithyroid drug therapy plus potassium iodide for 15 days (Protocol 2). At 10-yr follow-up, 50-60% of patients were euthyroid. 25-29% of patients required 2 doses of 131I, and 4-5% required 3 doses. Fewer patients became hypothyroid when their pretreatment FTI was above the average value. More patients became hypothyroid, if their pretreatment test for antimicrosomal antibodies was positive. Patients who required a second dose of radioactive iodide had a significantly greater chance of having worsening of their ophthalmopathy than those who became hypothyroid after the first dose. Treatment with radioactive iodide under either protocol appears to achieve euthyroidism at 10 yr with an incidence higher than that achieved by antithyroid drugs and comparable to that reported for subtotal thyroidectomy.     

Optimized radioiodine therapy of Graves' disease: analysis of the delivered dose and of other possible factors affecting outcome.

The best approach to radioiodine dose selection in the treatment of Graves' hyperthyroidism remains highly controversial. The formula to calculate the individual dose of (131)I to be delivered has been used for half a century and takes into account the thyroid mass, the effective half-life and the maximum uptake of (131)I. The objective of the present study was to evaluate the accuracy of this formula by determining the relationship between the administered dose of (131)I calculated to deliver a target dose of 50Gy to the thyroid and the actual exact organ dose. We further analyzed if therapeutic success, defined by euthyroidism following the individually calculated dose, can be predicted by different pretreatment parameters and particularly by organ dose. One hundred patients with a first episode of Graves' disease and who had received optimal thyroid irradiation after precise dosimetry were retrospectively reviewed. The patients were categorized according to their thyroid function (plasma free thyroxine (T(4)) serum concentration) as eu-, hyper- or hypothyroid during and 1 year after treatment. The relationship between the administered dose and organ dose was assessed by simple regression. We compared free T(4), free tri-iodothyronine, thyroid weight, the number of patients with antithyroperoxidase antibodies and TSH receptor autoantibodies, 24h urinary iodine excretion, (131)I uptake, and the exact dose of (131)I delivered to the thyroid as pretreatment variables. Although we found a correlation between administered dose (mCi) and organ dose (Gy) (r=0.3, P=0.003), the mean coefficient of variation for organ dose was 45%. Individualized radioiodine therapy enabled euthyroidism in 26% of patients and failed in 74% of patients (33% had persistent or recurrent hyperthyroidism and 41% permanent hypothyroidism). (131)I uptake was significantly higher in the hyperthyroidism group in comparison with the euthyroid group. However, organ dose and other pretreatment variables did not differ among the three groups. In conclusion, these results confirm the low performance of individual dosimetry using what are established ratios, since the delivered dose to the gland, although correlated to the intended dose, is highly variable. The finding that other usual pretreatment variables are not different between groups, gives little hope for improving the way of calculating the ideal dose of radioiodine. We suggest to those not yet ready to give a standard or an ablative dose for Graves' hyperthyroidism that they abandon this way to calculate the (131)I dose.     

The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study

The effect of antithyroid drugs on the efficacy of radioiodine (131I) treatment is still controversial. This study evaluated the effect of methimazole pretreatment on the efficacy of 131I therapy in Graves' hyperthyroidism. Sixty-one untreated patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/d; 29 patients). 131I was administered 4 d after drug discontinuation. The calculated 131I dose was 200 microCi/g thyroid tissue as estimated by ultrasound, corrected by 24-h radioiodine uptake. Serum TSH, T4, and free T4 were measured 4 d before 131I therapy, on the day of treatment, and then monthly for 1 yr. Considering cure as euthyroidism or hypothyroidism, based on free T4 measurement, approximately 80% of patients from both groups were cured 3 months after beginning 131I treatment. After 1 yr the groups were similar in terms of persistent hyperthyroidism (15.6% vs. 13.8%), euthyroidism (28.1% vs. 31.0%), or hypothyroidism (56.3% vs. 55.2%). Relapsed patients presented larger thyroid volume (P = 0.002), higher 24-h radioiodine uptake (P = 0.022), and T3 levels (P = 0.002). Multiple logistic regression analysis identified T3 values as an independent predictor of therapy failure. In conclusion, pretreatment with methimazole had no effect on either the time required for cure or the 1-yr success rate of 131I therapy.     

Recombinant TSH in ablative therapy and follow-up of patients with differentiated thyroid carcinoma

The studies evaluating the efficacy and safety of recombinant TSH in the ablative therapy and follow-up of patients with differentiated thyroid carcinoma by serum thyroglobulin (Tg) measurement and iodine scanning were reviewed in this article. Recombinant TSH is comparable to hypothyroidism in the generation of Tg and in the execution of iodine-131 whole-body scanning, with the advantage of sparing patients from the symptoms of hypothyroidism and from impaired quality of life induced by levothyroxine withdrawal, in addition to a reduced exposure to elevated TSH and shorter absence from work, with recombinant TSH being the preparation indicated for the diagnosis of metastases in both low risk (Tg after recombinant TSH) and moderate or high risk patients (Tg and iodine-131 scanning after recombinant TSH). In the case of ablative therapy, the results are promising when using a dose of 100 mCi for remnant ablation, but hypothyroidism is still preferred, except for patients in whom the desired TSH elevation after levothyroxine withdrawal is not achieved, patients with base diseases that are aggravated by acute and severe hypothyroidism (severe heart and lung disease, coronary disease, compromised renal function, history of psychosis due to myxedema), patients debilitated by advanced disease, and elderly individuals. The studies also show that the administration of recombinant TSH is safe, with few mild or moderate adverse effects.     

Surgical treatment of hyperthyroidism: a ten-year experience.

Hyperthyroidism is treated either by antithyroid drugs, radioiodine (I131) or surgery. In Sweden, surgery is often performed in patients with large goiter or severe hyperthyroidism with infiltrative endocrine ophthalmopathy. To evaluate indications and results of surgical treatment, data from 380 patients operated on for hyperthyroidism at our department during 1986-1995 were analyzed. Twenty-six percent were referred for surgery because of failure of treatment with antithyroid drugs or I131. Ninety-one percent were subjected to subtotal thyroidectomy with a median remnant weight of less than 2 g. In the remaining patients, total thyroidectomy was performed. Transient vocal cord affection occurred in 2.6%, none of which was permanent. Prolonged postoperative hypocalcemia occurred in 3.1%, and permanent hypoparathyroidism in 1%. There was no difference in complication rate between subtotal or total thyroidectomy. In patients with Graves' disease, 5% worsened with regard to ophthalmopathy initially after surgery but later improved. Recurrent disease occurred in 2% of the patients, all of whom had undergone subtotal thyroidectomy. Surgery is not first-line therapy in all patients with hyperthyroidism. However, in experienced hands, surgery is a good therapeutic alternative that can be carried out with no mortality, few complications, and, provided that a minimal remnant is left, very few recurrences.     

Long-term follow-up of treatment of thyrotoxicosis by three different methods

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%. At 5 years, 18% were hypothyroid, the prevalence rising to 42% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7%. The rate of hypothyroidism at 5 years (38.5%) was higher than that found in the calculated dose group. A minimum 10-year follow-up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2%. The prevalence of hypothyroidism (2% at 5 years, 27.5% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of radioiodine (131-I) as definitive therapy in patients with autoimmune and non-autoimmune hyperthyroidism

We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was measured before and after therapy every 3-6 months up to 3 yr. Three years after therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3% hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%. Definitive hypothyroidism was significantly higher in GD (p<0.0001) than in TA and TMG patients. Overall, positive effect of RAI (definitive hypothyroidism or euthyroidism) was very high: 93.7% in TA, 81.1% in TMG and 87.1% in GD patients. Thyroid volume reduction was observed in all patients, but was higher in GD patients (mean reduction of 76%) and in TA patients (mean nodule reduction of 69%). In TMG, mean reduction was of 32%. The median activity of RAI received by the 86 cured patients was 555 MBq (15 mCi) compared to 407 Mbq (11 mCi) received by the 14 patients who remained hyperthyroid. No influence was found between outcome and clinical parameters at the moment of 131-I therapy. In conclusion, our results indicate that RAI therapy is highly effective and safe for the control of hyperthyroidism.     

Results of subtotal thyroidectomy for Graves' disease.

The objective of this study was to find the factors responsible for hypothyroidism after subtotal thyroidectomy for Graves' disease. Two hundred five patients who were operated on from July 1989 to December 1997 were studied. The mean age of patients was 33.4+/-11.0 (mean +/- SD) years, and 175 (85.4%) were female. Patients were prepared with an antithyroid drug and Lugol's solution preoperatively. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyrotropin-binding immunoglobulins (TBII) antimicrosomal antibodies (AMA = 100x 4(M-1)), and antithyroglobulin antibodies (ATA = 100x4(T-1)) were measured 1 week before patients were operated on. Operations were performed according to the standard procedure with 2.5x1x1 cm of thyroid tissue remaining on each side before approximating the thyroid capsule and pretracheal fascia. Hypothyroidism was defined by patients with overt hypothyroidism in laboratory data, and or with T4 to maintain T3 and T4. Two hundred two patients were checked 3 months after being operated on. Latent hyperthyroidism was found in 22, euthyroidism in 55, latent hypothyroidism in 91, hypothyroidism in 34 (16.8%) and none were in overt hyperthyroidism. After a follow-up period of 26.9+/-15 (mean +/- SD) months, 199 patients were reevaluated. Overt hyperthyroidism was found in 2 patients, latent hyperthyroidism in 12, euthyroidism in 97, latent hypothyroidism in 72, and hypothyroidism in 16 (8%). Factors having possible effects on hypothyroidism after longterm follow-up were analyzed. Patient's age, gender, body surface, premedicative T3 and T4, preoperative ATA, and TBII, and the weight of removed thyroid had no effect on the occurrence of hypothyroidism. Preoperative AMA levels, and finding more than 10 lymphoid infiltrations per 10 low-power fields (x40) were significantly different between the hypothyroid and nonhypothyroid groups. A high level of preoperative AMA was the only factor independently causing overt hypothyroidism in the follow-up period. Patients with high preoperative AMA levels have a higher risk of hypothyroidism if only 2.5x1x1 cm remnants are left on each side.     

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

Abstract. Objectives . To investigate the long-term effect of radioactive iodine (¹³¹I) on thyroid function and size in patients with Graves' disease. Setting . Out-patient clinic in Herlev Hospital. Subjects . One hundred and seventeen consecutive patients (104 women) with Graves' disease selected for ¹³¹I treatment and followed for a minimum of 12 months (range 1–10 years, median 5 years). Interventions . ¹³¹I dose was calculated based on thyroid volume and 24-h ¹³¹I uptake. Main outcome measures . Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. Results . Seventy-eight patients were cured by one ¹³¹I dose and 30 by two doses, while the remaining nine patients received additional doses (range one to five doses, median one dose). Within one year, 25% developed hypothyroidism, and hereafter, hypothyroidism developed at a constant rate of 3% per year independent of antithyroid pretreatment. The cumulative 10-year risk of hypothyroidism was 60%. Initial median thyroid volume was 33 mL (range 9–106 mL). At 12 months after the last ¹³¹I dose, median thyroid volume was reduced to 14 mL (range 6–36 mL) (P < 0.00001). The median reduction being 58% (range 0–80%,), hereafter no further reduction occurred. A significant reduction in thyroid volume was also noted in patients needing subsequent ¹³¹I doses and in those developing hypothyroidism within the first year. Conclusions . ¹³¹I normalizes thyroid volume in patients with Graves' disease. Hypothyroidism seems an inevitable end result of this treatment. The present study suggests that it will be impossible to modify ¹³¹I therapy in a way to achieve both early control of hyperthyroidism and a low incidence of hypothyroidism.     

Use of thyroid ultrasound volume in calculating radioactive iodine dose in hyperthyroidism.

One hundred twenty-one patients treated with 131I had a thyroid ultrasound to measure thyroid volume precisely. This volume measurement was used to determine the radioactive iodine dose. The average size (+/-SEM) of the thyroid glands measured in this manner was 39.7 cm3 +/- 1.9 cc. A significant correlation was found in the estimated size of the gland by the endocrinologists and the ultrasound volume. Of the 121 patients, 89 patients had the same 131I microcurie per gram of tissue factor to determine the radioactive iodine dose. This group of patients was further evaluated in this study. The average 131I dose (+/-SEM) given was 13.2 mCi +/- 0.5 mCi. The average time until hypothyroidism was achieved 2.85 +/- 0.14 months. Ultrasound provides a safe and precise way to determine actual thyroid size when calculating 131I doses.     

STANDARD DOSE 131I THERAPY FOR HYPERTHYROIDISM CAUSED BY AUTONOMOUSLY FUNCTIONING THYROID NODULES

Thirty-one patients with hyperthyroidism shown on scintigram to have autonomously functioning thyroid nodules were treated with a standard dose of 15 milliocuries (mCi) of 131I. Of thirty patients who have been followed up for a least 6 months to over 3 years, all but one patient were euthyroid after a single dose. Repeat scintigram and Thyrotropin Releasing Hormone (TRH) test after therapy confirmed that twenty-five patients were cured of the disease. Only one patient developed hypothyroidism. This simplified standard dose regimen of radioiodine is effective in the treatment of hyperthyroidism caused by autonomously functioning nodules and is not complicated by the high incidence of hypothyroidism that is observed following radioiodine therapy of Graves' disease.     

Autoimmunization and multinodular large toxic goiter therapy using repeated doses of 131I

The radioiodine therapy can favour and induces of autommunological reaction in thyroid gland. The aim of the study was evaluation of antithyroid autoantibodies in patients with multinodular large toxic goiter treated with repeated doses of 131I before and after therapy. Studies were conducted in 24 women (age range: 65-84 yrs) with multinodular large toxic goiters--goiter volume assessed by USG over 100 ml. Serum TSH, fT4, antithyroid antibodies (anti-TPO, anti-Tg, TSHR-Ab) levels were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy. These studies and therapy with 22 mCi 131I were repeated every 3 months. Before therapy median of thyroid volume was approximately 195 ml and during therapy gradually decreased to 110 ml after 12 months. After 12 months we found 11% of patients with hyperthyrodism, 62% of patients with euthyroidism and 27% of patients with hypothyroidism. Before radioiodine treatment aTg and aTPO presence were detected in the most of patients, but only in 5 cases above normal value. TSHRAb were detected (normal, very low values) in 16 patients. During therapy statistically significance increase of TSHRAb levels (median: from 0,27 to 0,65 after 6 months and to 0,71 IU/l after 9 months) was observed; aTPO and aTg antibodies levels showed marked tendency to rise, but without significant differences (aTPO median: from 40 IU/ml to 48 IU/ml; aTg - median: from 27 IU/ml to 46 IU/ml). During these observations we didn't find evident correlation between the levels of antithyroid antibodies, radioiodine uptake, proved reduction of goiter volume and TSH, FT4, FT3 values.     

Long-term follow-up study of radioiodine treatment of hyperthyroidism

OBJECTIVE: To determine the cumulative incidence of hypothyroidism during long-term follow-up in patients treated for hyperthyroidism by radioactive iodine (131)I (RAI) therapy, the significance of clinical factors in predicting the development of hypothyroidism, and the outcome after a fixed 7 mCi (259 MBq) dose of RAI. DESIGN: Prospective cohort study of patients treated for hyperthyroidism by RAI. PATIENTS AND MEASUREMENTS: Since 1965, details on 2043 patients treated by RAI therapy in Tampere University Hospital were entered into a computerized register. Following RAI treatment, thyroid status was monitored every 1-3 months during the first year, and subsequently at 1-3-year intervals until June 2002 or until the patient died or moved out of the Tampere University Hospital district. results The cumulative incidence of hypothyroidism in patients with Graves' disease and toxic multinodular goitre at 1, 10 and 25 years was 24%vs. 4%, 59%vs. 15% and 82%vs. 32%, respectively. In a Cox regression model, previous partial thyroidectomy [risk ratio (RR) = 1.63 in patients with Graves' disease and RR = 1.59 in those with toxic multinodular goitre] and age at the first RAI treatment (RR = 0.998 and RR = 0.996 per year) were statistically significantly associated with the development of hypothyroidism both in patients with Graves' disease and in those with toxic multinodular goitre. Antithyroid medication preceding RAI therapy (RR = 0.47) decreased and female gender (RR = 1.53) increased the risk of hypothyroidism only in patients with Graves' disease. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 75% of patients, while two to six RAI treatments were needed in 25% of patients to achieve either a hypothyroid or a euthyroid state in both groups. None of the clinical factors studied was associated with the remission rate either in patients with Graves' disease or in those with toxic multinodular goitre. The remission rate did not differ between the patients who received a dose of RAI calculated according to the uptake of RAI and thyroid size and those who received an empirical dose of RAI. The fixed 7 mCi (259 MBq) dose of RAI cured 80% of patients. CONCLUSION: RAI treatment is effective in treating hyperthyroidism in patients with Graves' disease, but hypothyroidism will develop in 82% of patients in 25 years. Because the development of hypothyroidism seems to be inevitable and unpredictable by any clinical factors, the objective of RAI treatment should be to minimize the persistence of hyperthyroidism with the simplest possible form of treatment. We recommend a fixed 7 mCi dose of RAI to be used as the first empirical dose in the treatment of hyperthyroidism, at least in Graves' disease.     

Clinical and biochemical changes following 131I therapy for hyperthyroidism in patients not pretreated with antithyroid drugs

BACKGROUND: Radioiodine therapy (131I) for the treatment of hyperthyroidism has been shown to be effective and safe. Despite the extensive experience with radioiodine therapy, the necessity for pretreatment with antithyroid drugs is controversial. Pretreatment is partly based on the concept that antithyroid drugs deplete the thyroidal hormonal stores, thereby reducing the risk of a radioiodine-induced aggravation of hyperthyroidism or thyroid storm. Few data are available on the frequency of clinically significant exacerbations of hyperthyroidism following 131I therapy without prior treatment with antithyroid drugs. The aim of the present study was to determine prospectively the early clinical and biochemical changes after 131I therapy in patients who were not pretreated with antithyroid drugs. METHODS: Patients with Graves' disease (n = 21), toxic multinodular goiter (n = 11) or toxic adenoma (n = 2) were studied before and after 131I therapy. Clinical and biochemical parameters of thyroid function were investigated before and 1, 2, 8, 11, 18 and 25 days after 131I treatment. Patients were given no antithyroid drugs prior to 131I therapy, all patients received beta-blocking agents for symptomatic relief. RESULTS: In 19 of 34 patients, a transient increase in thyroid hormone levels was observed, predominantly in the first week following 131I therapy. None of these patients experienced worsening of thyrotoxic symptoms. This transient increase in thyroid hormone levels was demonstrated in all patients with toxic multinodular goiter, whereas it was found in only six of 21 patients with Graves' disease. This difference could not readily be explained by differences in pretreatment thyroid hormone levels, administered dose or effectively absorbed dose of 131I. CONCLUSIONS: 131I treatment of hyperthyroidism without pretreatment with antithyroid drugs may cause a transient increase in thyroid hormone levels. Clinically significant exacerbations of hyperthyroidism were, however, not observed in our study population. Increased hormone levels following 131I therapy were more often seen in patients with toxic multinodular goiter than in patients with Graves' disease.     

Treatment of Hyperthyroidism with Standard Doses of Radioiodine Aiming at Ablation

ABSTRACT Sixty patients with hyperthyroidism were treated with standard doses of ¹³¹I during 1969–83 in our department. The doses were 10–25 mCi (370–920 MBq), mostly 15 mCi (550 MBq). 38 of the patients have become hypothyroid, mostly within one year after treatment. There were 3 early relapses of hyperthyroidism; these patients became hypothyroid within one year after an additional dose of radioiodine. All hypothyroid patients had early substitution with l-thyroxine before overt clinical symptoms and signs had developed. There were no late relapses of hyperthyroidism. 15 patients had died during the follow-up; all were euthyroid or hypothyroid with adequate substitution. 28 of the 60 patients have been followed for 5–14 years, 14 for 2–5 years, 7 for 1–2 years and 10 for less than one year. Standard dose ¹³¹I treatment offers certain advantages compared with attempted individualized treatment. Late hypothyroidism after individualized dosage may be difficult to anticipate and detect, whereas early hypothyroidism after ablative standard dose treatment is easy to detect and control. Generally speaking, hypothyroidism is not to be regarded as a complication of radioiodine treatment for hyperthyroidism, but as its natural end result. The fixed dose schedule is especially well suited for regions where hyperthyroidism with no goitre or a small goitre is common.     

Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules

OBJECTIVE: To investigate the long-term effects of radioiodine (131I) on thyroid function and size in patients with a solitary toxic thyroid nodule. DESIGN: Prospective study of patients treated for a solitary autonomous toxic nodule, followed by evaluation of thyroid volume and function. PATIENTS: Sixty-two consecutive patients followed for a minimum of 12 months (range 12-168, median 60). Seventeen patients received antithyroid drug treatment before 131I. MEASUREMENTS: Standard thyroid function variables and ultrasonically determined thyroid volume before as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. RESULTS: 131I treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-h 131I uptake) was given as a single dose in 53 patients; six needed two doses and another three were given 3-5 131I treatments. The median initial dose was 310 MBq (140-666) and the median total dose was 332 MBq (148-1576). In patients receiving one 131I treatment (n = 53) the total thyroid volume decreased significantly from a median of 40 ml (range 19-77) to 24 ml (8-50) within 3 months. This represented a median reduction of 35%. A further significant decrease was seen after 24 months to a total reduction of 45%. In patients given more than one dose the thyroid volume was reduced from a median of 45 ml (19-104) before treatment to 30 ml (14-50) after a follow-up of 60 months (9-132) after the last 131I treatment. Patients without antithyroid pretreatment, receiving one 131I treatment (n = 39) became euthyroid after a median of 1.5 months (0.75-9) after treatment. Seventy-five per cent were euthyroid within 3 months. In patients pretreated with antithyroid drugs and treated with one dose of 131I (n = 14) euthyroidism was achieved after a median of 12 months (0.75-24) after 131I treatment. Hypothyroidism developed in five patients (8%) after a median of 36 months (6-60) after 131I treatment. CONCLUSION: A cure-rate of 75% within 3 months is seen when treating autonomous solitary toxic thyroid nodules with 131I. The thyroid volume is reduced by 35% within 3 months and 45% after 2 years. Side-effects are few and consist of hypothyroidism in less than 10% with a median follow-up of 5 years. This treatment should be regarded as the standard treatment for this condition until prospective comparisons with surgery and ethanol injection therapy have been performed.