Prediction of cure and risk of hypothyroidism in patients receiving 131I for hyperthyroidism

Context There is little consensus regarding the most appropriate dose of radioiodine (¹³¹I) to be administered to patients with hyperthyroidism. Objective To compare the efficacy of fixed dose regimens of ¹³¹I in curing hyperthyroidism and to define simple clinical and biochemical factors that predict outcome in individual patients. Design Consecutive series of hyperthyroid subjects treated with ¹³¹I. Setting Single Secondary/Tertiary Care Hospital Clinic. Participants A total of 1278 patients (1013 females and 262 males, mean age 49·7 years) presenting with hyperthyroidism between 1984 and 2006. Intervention Treatment with ¹³¹I using a fixed dose regimen. Main outcome measures Probability of cure and risk of development of hypothyroidism following a single dose of ¹³¹I. Results Patients given a single dose of ¹³¹I of 600 MBq (n = 485) had a higher cure rate (84·1%) compared with those receiving either 370 MBq (74·9%, P < 0·001) or those given 185 Bq (63%, P < 0·001). An increased incidence of hypothyroidism by 1 year was evident with higher doses (600 MBq: 60·4%; 370 MBq: 49·2%, P = 0·001; 185 Bq: 38·1%, P < 0·001). Binary logistic regression analysis identified a 600 Bq dose of ¹³¹I [adjusted odds ratio, AOR 3·33 (2·28–4·85), P < 0·001], female gender [AOR 1·75 (1·23–2·47), P = 0·002], lower presenting serum free T4 concentration [AOR 1·01 (1·01–1·02), P < 0·001] and absence of a palpable goitre [AOR 3·33 (2·00–5·56), P < 0·001] to be independent predictors of cure. Similarly, a 600 MBq dose [AOR 3·79 (2·66–5·38), P < 0·001], female gender [AOR 1·46 (1·05–2·02), P = 0·02], younger age [AOR 1·03 (1·02–1·04), P < 0·001], absence of a palpable goitre [AOR 3·85 (2·38–5·88), P < 0·001] and presence of ophthalmopathy [AOR 1·57 (1·06–2·31), P = 0·02] were identified as independent factors predicting the probability of development of hypothyroidism at one year. Based on these findings, formulae to indicate probability of cure and risk of hypothyroidism for application to individual patients were derived. Conclusions Simple clinical/biochemical criteria can be used to predict outcome after ¹³¹I treatment. These factors determine that males, those with severe biochemical hyperthyroidism, and those with a palpable goitre require larger doses (600 MBq) in order to achieve cure.     

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.     

Radioiodine treatment of hyperthyroidism-prognostic factors for outcome

There is little consensus regarding the most appropriate dose regimen for radioiodine (131I) in the treatment of hyperthyroidism. We audited 813 consecutive hyperthyroid patients treated with radioiodine to compare the efficacy of 2 fixed-dose regimens used within our center (185 megabequerels, 370 megabequerels) and to explore factors that may predict outcome. Patients were categorized into 3 diagnostic groups: Graves' disease, toxic nodular goiter, and hyperthyroidism of indeterminate etiology. Cure after a single dose of 131I was investigated and defined as euthyroid off all treatment for 6 months or T4 replacement for biochemical hypothyroidism in all groups. As expected, patients given a single dose of 370 megabequerels had a higher cure rate than those given 185 megabequerels, (84.6% vs. 66.6%, P < 0.0001) but an increase in hypothyroidism incidence at 1 yr (60.8% vs. 41.3%, P < 0.0001). There was no difference in cure rate between the groups with Graves' disease and those with toxic nodular goiter (69.5% vs. 71.4%; P, not significant), but Graves' patients had a higher incidence of hypothyroidism (54.5% vs. 31.7%, P < 0.0001). Males had a lower cure rate than females (67.6% vs. 76.7%, P = 0.02), whereas younger patients (<40 yr) had a lower cure rate than patients over 40 yr old (68.9% vs. 79.3%, P < 0.001). Patients with more severe hyperthyroidism (P < 0.0001) and with goiters of medium or large size (P < 0.0001) were less likely to be cured after a single dose of 131I. The use of antithyroid drugs, during a period 2 wk before or after 131I, resulted in a significant reduction in cure rate in patients given 185 megabequerels 131I (P < 0.01) but not 370 megabequerels. Logistic regression analysis showed dose, gender, goiters of medium or large size, and severity of hyperthyroidism to be significant independent prognostic factors for cure after a single dose of 131I. We have demonstrated that a single fixed dose of 370 megabequerels 131I is highly effective in curing toxic nodular hyperthyroidism as well as Graves' hyperthyroidism. Because male patients and those with more severe hyperthyroidism and medium or large-sized goiters are less likely to respond to a single dose of radioiodine, we suggest that the value of higher fixed initial doses of radioiodine should be evaluated in these patient categories with lower cure rates.     

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism

Background and objectives The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. Patients and design We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4‐h ¹²³I uptake and the outcome of ¹³¹I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. Results The diagnostic categories were Graves’ disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves’ disease coexisting with nodules (n = 81). The mean age of the patients was 58 ± 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0·60, 95% CI 0·57–0·64, P < 0·001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0·98) or radioiodine uptake at 4 h (P = 0·2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2·0, 95% CI 1·2–3·6, P = 0·01). Conclusion Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.     

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.     

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.     

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.     

ACUTE EFFECT OF INORGANIC IODIDE AFTER 131I THERAPY FOR HYPERTHYROIDISM

Patients treated with inorganic iodide weeks to years following ¹³¹I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after ¹³¹I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9-14 days following ¹³¹I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after ¹³¹I administration; eight received only ¹³¹I. Serum T4 and T3 concentrations did not change significantly in the patients who received only ¹³¹I. In the patients who received ¹³¹I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2-10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that ‘escape’ from the acute antithyroid effect of iodide occurs when it is given immediately after ¹³¹I therapy, thus limiting the utility of iodide as a therapeutic agent at this time. ¹³¹I-iodide is a widely used and effective form of therapy for hyperthyroidism. Reduction in thyroid hormone does not occur within the first weeks after ¹³¹I therapy. Exacerbation of hyperthyroidism may occur shortly after ¹³¹I administration, with frequency ranging from 0 to 11% in several large species (Chapman et al., 1954; Cassidy & Astwood, 1959; Lamberg et al., 1959; Green & Wilson, 1964). Such exacerbations are thought to reflect acute thyroid radiation necrosis and subsequent hormone release, and may limit the use of ¹³¹I therapeutically. Inorganic iodide is a rapidly, but usually transiently, effective antithyroid agent when used alone. No reports are available concerning the efficacy of iodide when given immediately following ¹³¹I therapy. Since some hormone release after ¹³¹I therapy may reflect thyroid destruction, rather than secretion, it is possible iodide might be less effective in this setting. On the other hand, if iodine is effective immediately after ¹³¹I therapy, especially if its action is sustained (as occurs in patients treated with ¹³¹I months or years previously; Hagen et al., 1967; Braverman et al., 1969), it might be a useful adjunct for certain hyperthyroid patients treated with ¹³¹I. This report describes the result of a study of patients so treated.     

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroldism led us to perform a study in order to compare a fixed dose regime comprising doses of 185, 370 or 555 MBq based on gland size assessment by palpation only, with a calculated ¹³¹I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour ¹³¹I uptake determination. DESIGN Prospective randomized study. PATIENTS Two hundred and twenty-one consecutive hyperthyroid patients referred for ¹³¹I treatment. Four patlents who dled for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remalnlng 163 patlents (143 women) were studied, dlvlded into subgroups accordlng to the type of gland. They all recelved antithyroid drugs prior to ¹³¹I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS Thyroid function variables were determined approximately 2 weeks before ¹³¹I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to ¹³¹I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of ¹³¹I was carried out. Thyroid in 78 of the 163 patients. Twelve months after the initial ¹³¹I dose patients could be classified as euthyroid, hyperthyrold or hypothyroid. RESULT Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthroid. Seven of 78(9%) in the calculated dose group were classified as permanently hypothyroid. Finally, 39 of 78(50%) In the calculated dose group and 49 of 85(58%, NS) in the fixed group were enthyroid at 12 months after ¹³¹I treatment. One year after ¹³¹I therapy thyroid volume was deduced from 59.3 ± 9.2 (mean ± SEM) to 36.2 ± 6.6 ml (average reduction 39%) In the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 ± 6.1 to 41.17 ± 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS A semiquantitative approach is probably as good as the more elaborately calculated radiolodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.     

Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves' hyperthyroidism

Radioiodine (131I) is the preferred definitive treatment for Graves' hyperthyroidism. Pretreatment with antithyroid drugs is often used to avoid thyroid hormone discharge after 131I ablation. However, this may represent an unnecessary increase in risk and costs. Fifty-one patients with Graves' disease were randomly assigned to receive 131I alone (28 patients) or 131I plus pretreatment with methimazole (30 mg/day; 23 patients). Methimazole was interrupted 4 days before 131I therapy. Serum T4, free T4 (FT4), and T3 were measured on days -4 and -1, on the day of treatment, and on days 2, 5, 7, 14, 20, and 30. In patients receiving 131I alone, mean serum T4 levels did not change after therapy. Mean serum FT4 and T3 levels decreased significantly 5 days after 131I administration (15% and 18%, respectively). Serum T3 reached its lowest level on day 30 (38%). With pretreatment, mean serum T4, FT4, and T3 levels increased (38%, 39%, and 70%, respectively) after methimazole discontinuation and before 131I administration. After 131I, serum T4 levels peaked on day 7 (23% vs. treatment day; 70% vs. baseline); FT4 levels peaked on day 14 (53% vs. treatment day; 107% vs. baseline). The serum T3 concentration increased 9% on day 2 (85% vs. baseline) and decreased from day 14 (15%) to day 30 (21%). We conclude that interruption of antithyroid drugs causes a short term increase in serum thyroid hormone levels in patients with Graves' hyperthyroidism receiving 131I. Thyroid hormone levels stabilize or decrease during the first 30 days after 131I therapy.     

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.     

Effect of 131 I treatment on the calcitonin response to calcium infusion in hyperthyroid patients

OBJECTIVE The objective was to evaluate the effect of ¹³¹I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. DESIGN Determination of basal calcitonin levels and calcitonin secretory reserve before and aiter ¹³¹I administration. PATIENTS Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after ¹³¹I treatment, and 12 of these patients were restudied 8 months after ¹³¹I treatment. MEASUREMENTS Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. RESULTS The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before ¹³¹I treatment (10.9·2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6·0.7 and 1.6·0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. CONCLUSION Our results demonstrate that ¹³¹I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency.     

Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.

The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either hypothyroidism or TRAb-associated hyperthyroidism, were seen in 8 of 20 patients (40%) with anti-TPO before 131I treatment, compared to 9 of 129 (7%) without (p<0.005). In conclusion, TRAb and a Graves' like hyperthyroidism can be triggered by 131I treatment in patients with nodular toxic goiter. The presence of anti-TPO seem to be a marker of an increased risk of development of TRAb-associated hyperthyroidism as well as hypothyroidism, but both side effects can be seen despite the absence of anti-TPO autoantibodies.     

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.     

A novel mutation causing complete deficiency of thyroxine binding globulin

OBJECTIVE Recovery of thyroid function in patients following hypothyroidism induced by ¹³¹I therapy for Graves' disease has been described, but only a few detailed clinical and biochemical studies of this phenomenon (transient hypothyroidism) have been published. The prevalence, mechanism, and final outcome of transient hypothyroidism in 260 patients with Graves’ disease treated with ¹³¹I was studied. DESIGN A retrospective study. PATIENTS Two hundred sixty patients with Graves' disease, treated with ¹³¹I between 1 and 15 years previously, were categorized into 4 groups according to their thyroid function during and 1 year after therapy (Group 1: permanent hypothyroidism, 28 patients; Group 2: transient hypothyroidism, 39 patients; Group 3: euthyroidism without transient hypothyroidism, 83 patients; Group 4: hyperthyroidism, 110 patients). MEASUREMENTS We compared total T4, total T3, TSH, anti-thyroglobulin (TGHA) and anti-microsomal (MCHA) antibodies, the TSH-binding inhibitory immunoglobulin (TBII) index, thyroid weight, dose of ¹³¹I, and 24-hour ¹³¹I uptake as pretreatment variables. The mean time for permanent hypothyroidism to develop was estimated by the Kaplan–Meier product limit method. The TBII index and thyroid stimulating antibody (TSAb) activity were measured in seven patients from Group 1 and in nine patients from Group 2 at the time that they became hypothyroid. RESULTS Hypothyroidism developing within 12 months of therapy was transient in 58% (39/67) of patients. No pretreatment variables were found to differ between patients with and without transient hypothyroidism. The mean estimated time between therapy and the development of permanent hypothyroidism was 96 months in Group 2; this time interval was significantly shorter than 126 months in Group 3 and 129 months in Group 4 (P<0.05, P<0.01, respectively). TSAb activity was > 500% in 78% (7/9) of patients from Group 2, which was significantly higher than that found (14%, 1/7) in Group 1. CONCLUSIONS These results indicate that (1) more than half the patients who developed hypothyroidism within 6 months after ¹³¹I treatment for Graves' disease recovered spontaneously, (2) TSAb activity might play some role in the recovery of transient hypothyroidism, and (3) the development of transient hypothyroidism may influence long-term thyroid function.     

Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study

OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.     

Hypothyroidism after iodine-131 or surgical therapy for Graves' disease hyperthyroidism

BACKGROUND: The aim of this work was to describe late permanent hypothyroidism after iodine-131 or surgery, and to seek predictive factors of hypothyroidism for the two treatments. MATERIAL: From 1979 to 1994, 462 patients with Graves' disease hyperthyroidism underwent definitive treatment. Three hundred and fifty-five patients were treated with low calculated doses of iodine-131, and 107 patients with subtotal thyroidectomy. Life-table analysis was performed and the cumulative incidence of hypothyroidism was calculated by Kaplan-Meier's method, and survival (euthyroidism) within the groups was compared by the Mantel-Cox method. RESULTS: Of the 355 patients treated with one dose of 6.6 1.9 mCi of iodine-131, 246 became euthyroid after one dose, and 109 needed 2 or more doses. Twenty-two patients received one or more doses higher than 10 mCi. The probability of euthyroidism at 145 months after low-dose was 10. 19% and age, sex, pretreatment with antithyroid drugs, previous subtotal surgery did not influence the final outcome. Of the 107 surgically treated patients the probability of euthyroidism at 144 months was 56.1%. Age, sex, duration of hyperthyroidism, duration of antithyroid treatment, weight of thyroid resected, did not influence the final outcome. The weight of the thyroid remnant was 5.4 1.5 g and the multivariate statistical model by conditional logistic regression showed that the weight of thyroid remnant was the only variable that influenced long-term thyroid function. CONCLUSIONS: There is no ideal dose of iodine-131 that would correct hyperthyroidism in Grave? disease without risk of hypothyroidism. Surgery is an alternative definitive treatment with a risk of hypothyroidism within the 2 first years, and a cumulative risk of hypothyroidism lower than with iodine-131.     

Standardized radioiodine therapy in Graves' disease: the persistent effect of thyroid weight and radioiodine uptake on outcome

Abstract. Objective. To assess the incidence of hypothyroidism, euthyroidism, and recurrent hyperthyroidism following a standard dose of Na¹³¹I (3.7 MBq or 100 μCi) per g thyroid tissue, adjusted for radioiodine tracer uptake. Design. A single-centre prospective follow-up study from January 1990 to December 1992. Setting. Academic Hospital in Utrecht, the Netherlands. Subjects. Newly diagnosed patients with Graves' disease (n = 148). Interventions. Radioiodine treatment at a standard dose of 3.7 MBq or 100 μCi per g thyroid tissue. Main outcome measures. Confidence interval testing of resulting thyroid status, defined by biochemical criteria. Results. The overall cure rate was 70% (103 of 148 subjects), confidence interval (CI) 62–77%. A 90% incidence of hypothyroidism was found in patients with a small thyroid (less than 20 g). Recurrent hyperthyroidism was found significantly more often in subjects with a thyroid weight exceeding 60 g compared to those who had a thyroid of 9–59 g. More recurrences were found in subjects in the highest tertile of a 24-h radioiodine uptake test (> 80% uptake) compared to those in the lowest tertile (< 60% uptake). Conclusions. No uniform treatment results expressed per thyroid weight category were obtained, in spite of standardizing the treatment Na¹³¹I dose (3.7 MBq per g thyroid). Graves' patients with a thyroid smaller than 20 g and those with less than 60% 24-h radioiodine uptake have a 50–90% chance of hypothyroidism at the 12-month follow-up.     

Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists

Objective To investigate how North American thyroidologists assess and treat amiodarone‐induced thyrotoxicosis (AIT) and to compare the results with those of the same questionnaire‐based survey previously carried out among European thyroidologists. Design Members of the American Thyroid Association (ATA) with clinical interests were sent by e‐mail a questionnaire on the diagnosis and management of AIT, 115 responses were received from the United States and Canada, representing about one‐third of ATA members with clinical interests. Results The majority of respondents (91%vs. 68% in Europe, P < 0·05) see < 10 new cases of AIT per year, and AIT seems less frequent than amiodarone‐induced hypothyroidism (AIH) in North America (34% and 66% of amiodarone‐induced thyroid dysfunction, respectively, vs. 75% and 25%, respectively, in Europe, P < 0·001). When AIT is suspected, in North America hormonal assessment is mostly based on serum free T4 (FT4) and TSH measurements, while serum free T3 (FT3) determination is requested less frequently than in Europe; thyroid autoimmunity is included in the initial assessment less than in Europe. Most commonly used additional diagnostic procedures include, as in Europe, thyroid colour‐flow Doppler sonography, and to a lesser extent, thyroid radioactive iodine uptake and scan, but Europeans tend to request multiple tests more than North Americans. Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists (21%vs. 10% in Europe in type 1 AIT, P < 0·05, 34%vs. 20% in type 2 AIT, P < 0·05). In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans, but the former use them as monotherapy in 65%vs. 51% of Europeans (P < 0·05) who more often consider potassium perchlorate as an useful addition (31%vs. 15% of North Americans, P < 0·01). Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0·05) or in association with thionamides (16%vs. 25% in Europe, P = NS). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans. If amiodarone therapy needs to be reinstituted, prophylactic thyroid ablation is advised by 76% in type 1 AIT, while a ‘wait‐and‐see’ strategy is adopted by 61% in type 2 AIT, similar to behaviour of European thyroidologists. Conclusion Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.     

Features at diagnosis of 324 patients with acromegaly did not change from 1981 to 2006: acromegaly remains under‐recognized and under‐diagnosed

Background Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown, so we tested if disease severity at diagnosis had changed from 1981 to 2006. Methods Data on 324 consecutive acromegaly patients presenting from 1981 to 2006 at two New York City hospitals were collected by retrospective review (n = 324) and by interview (n = 200). The main complaint, acromegaly associated comorbidities, signs, symptoms, healthcare providers visited, preoperative GH and IGF‐I levels and pituitary tumour size at diagnosis were compared in patients presenting in the earlier vs. later halves of the time period. Results Times from symptom onset to diagnosis were 5·9 year (early) vs. 5·2 year (late; P = NS). At diagnosis, 96% of early and late groups had facial feature changes and/or hand/foot enlargement. Comorbidities included hypertension 37% (early) vs. 36% (late), carpal tunnel syndrome (24%vs. 24%), sleep apnoea (13%vs. 29%; P < 0·01), osteoarthritis (25%vs. 23%) and diabetes mellitus (18%vs. 15%); each patient had 1·2 (early) vs. 1·3 (late; P = 0·53) comorbidities. Groups were similar in signs, symptoms, tumour size, GH and IGF‐I. Conclusions Clinical, biochemical and tumour size characteristics at diagnosis of acromegaly patients were unchanged from 1981 to 2006. Most patients still have marked manifestations of acromegaly at diagnosis, suggesting that acromegaly remains clinically under‐recognized. Healthcare professionals should more commonly consider acromegaly, which can lead to earlier diagnosis and better treatment outcome.