Appearance of anti TSH-receptor antibodies and clinical Graves' disease after radioiodine therapy for hyperfunctioning thyroid adenoma

Radioiodine treatment use is frequent in patients with benign hyperfunctioning thyroid diseases and the side-effects are rare. In this paper we described the appearance of TSH-receptor antibodies and the concomitant development of persistent hyperthyroidism in a patient with hyperfunctioning thyroid adenoma after 131I treatment. A 70-year-old man presented a hyperfunctioning thyroid adenoma with suppressed uptake in the adjacent normal gland. Antibodies against the thyroglobulin (TgAb), thyroid peroxidase (TPOAb) and TSH-receptor (TRAb) were absent. One year after remission by radioiodine therapy the patient developed severe and persistent hyperthyroidism associated with diffuse 131I uptake in the gland. TgAb and TPOAb remained absent, but TRAb were present. Although spontaneous development of Graves' disease cannot be excluded, the time sequence and the negative familial and personal history for autoimmune diseases suggest a possible connection between the two phenomena. The release of TSH-receptor antigen from follicular cells damaged by 131I may have triggered the autoimmune response turning a toxic nodular goiter patient into a Graves' disease patient.     

Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH

This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres. The feasibility of ¹³¹I therapy depends on an adequate thyroid ¹³¹I uptake. Based on a two-fold increase in thyroid ¹³¹I uptake, superiority studies have convincingly demonstrated that the absorbed thyroid ¹³¹I dose can be increased without increasing the administered ¹³¹I activity, resulting in a 35–56% amplification of goitre reduction at one-year post radioiodine compared to conventional (without rh-TSH) ¹³¹I therapy. Although patient satisfaction is not improved at one-year, this approach facilitates tracheal decompression and is particularly promising in large goitres. The majority of multinodular non-toxic goitre patients may not require amplified goitre reduction. But as an alternative strategy, rh-TSH allows up to 80% reduction of the therapeutic ¹³¹I activity while still achieving goitre reduction comparable to that of conventional ¹³¹I therapy and maintaining high patient satisfaction. The dose-reduction (equality) strategy is attractive in terms of minimizing post-therapeutic restrictions and in reducing the potential risk of radiation-induced malignancy. Adverse effects like temporary thyroid swelling and thyroid hormone excess are to a large extent dose-dependent and generally 0.1 mg rh-TSH or less is well tolerated. Based on these results we conclude that rh-TSH augmented ¹³¹I therapy is a promising new therapeutic principle allowing the tailoring of an optimal ¹³¹I therapy on the individual level.     

TSH-receptor autoantibodies - differentiation of hyperthyroidism between Graves' disease and toxic multinodular goitre.

Previous studies indicate pre-existing subclinical Graves' disease in many patients with the scintigraphic diagnosis of toxic multinodular goitre type A, equivalent to the in Germany so-called disseminated thyroid autonomy. Furthermore, after radioiodine treatment an increase or the induction of TSH-receptor antibodies (TRAb) in patients with Graves' disease or toxic multinodular goitre has been repeatedly reported. The distinction between both hyperthyroid conditions, Graves' disease and toxic multinodular goitre type A, depends on the diagnostic power of the TSH-receptor antibody determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay based on competitive binding to recombinant human TSH-receptor showed a higher sensitivity for the detection of TSH-receptor antibodies in patients with Graves' disease than previous assays using solubilized porcine epithelial cell membranes. In up to 50 % of patients with toxic multinodular goitre A without antithyroid drug pretreatment TSH-receptor antibodies were detectable with a high correlation between thyroid-stimulating antibodies in the bioassay and the h-TBII assay. Moreover, in a recent study the development of TSH-receptor antibodies after radioiodine treatment was detectable in 36 % of patients with toxic multinodular goitre type A, whereas TSH-receptor antibodies were not detectable in patients with toxic multinodular goitre type B or in patients with toxic adenoma. In conclusion, thyroid-stimulating antibodies in a bioassay or TSH-receptor antibodies detected with the h-TBII assay have the highest diagnostic power to differentiate Graves' disease from toxic multinodular goitre. Because of its less cumbersome assay technique the h-TBII should be performed in all patients with hyperthyroidism to differentiate Graves' disease from non-autoimmune hyperthyroidism such as toxic multinodular goitre to select the appropriate therapy for these patients.     

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.     

THYROID FUNCTION IN PATIENTS WITH EXOPHTHALMOS PRECEDING THYROTOXICOSIS

Eight patients are described who showed the classical ocular manifestations of Graves' disease but none of the other clinical manifestations of hyperthyroidism. In all cases there was an elevated level of PB¹³¹I in the plasma after the administration of a tracer dose of ¹³¹I, and, in three cases studied, the uptake of ¹³¹I by the thyroid was not suppressed by the administration of triiodothyronine. The possible mechanisms are discussed.     

Acute changes in thyroid volume and function following 131I therapy of multinodular goitre

OBJECTIVE Many textbooks claim that radioIodine (¹³¹I) treatment should be given with care to a goitre with substernal extension, for fear of acute swelling of the gland and thus respiratory problems. Since ¹³¹I Is used increasingly in the treatment of non-toxic as well as toxic goitre we have evaluated the acute changes in thyroid volume following ¹³¹I therapy. DESIGN Evaluation of potential acute changes in thyroid volume and function after ¹³¹I treatment in patients with non-toxic goitre treated because of compression symptoms or for cosmetic reasons, as well as In patients with toxic goitre. PATIENTS Out-patients with multinodular goitre, either non-toxic (n= 20) or toxic (n= 10). Excluded were patients with a substernal goitre. MEASUREMENTS Ultrasonically determined thyroid volume and standard thyroid function variables were Investigated before and 2, 7, 14, 21, 28 and 35 days after treatment. RESULTS In non-toxic goitres the thyroid volume did not increase significantly, the maximum increase in the median volume being 4% on day 7. Serum levels of free T3 and free T4 Indices increased by 20% (day 7) and 13% (day 14) (P= 0·002), respectively. Likewise thyroid volume in toxic nodular goitre did not change significantly after ¹³¹I treatment (maximum median increase was 2%). None of the patients presented symptoms of tracheal compression. CONCLUSIONS ¹³¹I treatment of non-toxic as well as toxic multinodular goitre does not seem to increase thyroid volume.     

The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly

OBJECTIVE Graves' disease is recognized as an organ-specific autoimmune disorder caused by the presence of TSH receptor antibodies. The long-term effects of ¹³¹I treatment for Graves' disease on TSH receptor antibodies have not previously been studied. We have measured the TSH-binding Inhibitory immunoglobulin (TBII) Index and thyroid stimulating antibody (TSAb) activity in patients with Graves' disease following treatment with ¹³¹I. DESIGN A retrospective study. PATIENTS Two hundred and twenty-five patients with Graves' disease who were treated with ¹³¹I 1–13 years earlier were studied (1 year: 27 patients; 2–5 years: 42 patients; 6–9 years: 79 patients; 10–13 years: 77 patients). MEASUREMENTS The TBII index was measured as the percentage ¹²⁵I-TSH bound to pig thyroid membranes and TSAb activity as the amount of cAMP produced by cultured FRTL-5 cells. RESULTS TBII was detected in 78% of patients prior to ¹³¹I administration. Following ¹³¹I administration, the Incidence of positive TBII was 85% at the end of the first year decreasing to 40,19 and 17% at 2–5,6–9 and 10–13 years, respectively. The frequency of a positive TSAb was 74% at the end of the first year, and also decreased to 49, 27 and 29% at 2–5, 6–9 and 10–13 years, respectively. At more than 2 years after ¹³¹I therapy, the frequencies of hyperthyroidism In TBII and TSAb positive patients were 42% (19/45) and 30% (19/63), respectively, which were significantly higher than those In TBII and TSAb negative patients (8%: 12/153 and 8%:11/131, respectively). The frequency of hyperthyroidism after ¹³¹I treatment in patients with negative TBII before treatment (7%: 2/29) was significantly lower than that (29%: 30/102) In patients with positive TBII before treatment. CONCLUSIONS These results indicate that (1) the TBII Index and TSAb activity decreased over a period of more than 2 years after ¹³¹I therapy for Graves' disease, and (2) the TBII index before treatment may influence the long-term outcome of ¹³¹I therapy.     

Role of recombinant human TSH in the management of large euthyroid multinodular goitre: a new therapeutic option? Pros and cons

Conventional 131I treatment has been used in the last 20 years for large nodular goitres when patients present high surgical risk or simply refuse surgery. 131I therapy causes a mean goitre volume reduction of about 40% after one year. However, the individual response is variable and for low radioiodine uptake and very large goitres, high 131I activities are needed in order to have a adequate 131I accumulation in the thyroid. rhTSH is approved for thyroid cancer management and has been tested off label in large goitres, in whom increases 131I uptake, thus reducing the 131I amount to be administered. The use of lower 131I activities allows to reduce the radiation burden to body and the time of social life restriction. Moreover, depending on the radiation regulations of the different countries, the 131I therapy could be carried out either as outpatients or in a shorter hospitalization period, implying a decrease of costs. The effects of rhTSH on goitre may be due not only to the 131I uptake increase, but also to a more homogeneous distribution of 131I in the gland, and to the thyroid cell activation that makes them more radiosensitive. Acute adverse effects are due to the surge of thyroid hormone in blood and to the goitre volume increase, that cause cardiac symptoms and tracheal compression, respectively. These effects are probably dose dependent and are negligible for rhTSH lower doses.     

PRODUCTION OF NON-STIMULATORY IMMUNOGLOBULINS THAT INHIBIT TSH BINDING IN Graves'' DISEASE AFTER RADIOIODINE ADMINISTRATION

The effect of a single dose of ¹³¹I upon thyroid stimulating immunoglobulins has been studied in twenty-two patients with Graves' disease. The thyroid stimulating immunoglobulins were assessed by parallel measurements of thyrotrophin receptor binding inhibitory immunoglobulins (TBII) and of thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in serum by radioreceptor assay and stimulation of adenylate cyclase respectively. Prior to ¹³¹I therapy TBII were present in fourteen and TACSI in sixteen patients; seventeen were positive in one of the assays and thirteen in both assays. After radioiodine the level of both TACSI and TBII increased in most patients, but in six patients ¹³¹I therapy appeared to lead to a dissociation between the TBII and TACSI. After 12 months, nine patients were still positive in both assays, and twenty-one in one of the assays. In total, five patients developed hypothyroidism within 1 year after radioiodine. The TBII levels were significantly higher both before and 3 months after therapy in these patients than in those who remained euthyroid. Two of the hypothyroid patients developed non-stimulatory TSH binding inhibitory antibodies. The present study thus confirms that radioiodine therapy is followed by an increase of TBII and TACSI in most patients with Graves' disease. The level of TBII can probably provide a marker for development of hypothyroidism following ¹³¹I therapy and might be involved in its pathogenesis.     

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.     

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.     

Incidentally Visualization of the Thymus on Whole-Body Iodine Scintigraphy: Report of 2 Cases and Review of the Latest Insights

Radioiodine uptake is not commonly seen by the thymus gland. On the contrary, the gland is slowly replaced by fat after puberty. Herein, we present 2 patients with papillary thyroid carcinoma, follicular variant, and cervical lymph node involvement. After total/near-total thyroidectomy, the patients received ¹³¹I for ablation therapy. On posttreatment radioiodine scintigraphy, mediastinal ¹³¹I uptake was noted that finally was histologically/anatomically diagnosed as thymus gland uptake. It should be borne in mind as a potential cause of false-positive whole-body ¹³¹I scintigraphy.     

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.     

TSH unresponsiveness, a case report

A patient with congenital primary hypothyroidism is presented. His thyroid gland had a normal uptake of radioiodine which was independent of endogenous or exogenous TSH, sympathetic B-receptor blockade or prostaglandin inhibition. Infusion of dibuturyl-cyclic AMP increased the uptake of radioiodine and stimulated release of protein bound 131I. He had no goitre even when he did not receive thyroxine, but thyroid histology showed evidence of active epithelium in the presence of adequate substitution with thyroxine. We assume that some unknown factor other than TSH stimulates part of the glandular function in this patient, without leading to adequate formation and release of thyroid hormone.     

Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients: at diagnosis and following treatment

Objectives. To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment. Setting. Department of Endocrinology, Malmö University Hospital, Malmö, Sweden. Subjects and design. Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17–85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24–86 years). Interventions. Most patients were treated by radioactive iodine following the first blood sample. Main outcome measures. ICA and GAD-Ab in serum. Results. At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state. Conclusion . The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope.     

The effect of radioactive iodine treatment on thyroid C cells

To determine the effect of radioiodine treatment on thyroid C cells, calcitonin (CT) levels were measured by RIA before and after intravenous calcium stimulation (2 mg/kg body-weight elemental calcium) in 22 women treated with 131I for hyperthyroidism. The results were compared with sex, age and weight-matched normal controls. There was a slight but statistically significant decrease in basal CT levels of the patients compared to the control group (mean +/- SE; 0.009 +/- 0.001 vs 0.011 +/- 0.001 pmol/l, P less than 0.05). The mean stimulated CT level of the patient group was significantly lower than that of the controls (0.010 +/- 0.001 vs. 0.018 +/- 0.003 pmol/l, P less than 0.001). The absence or presence of 131I-induced hypothyroidism at the time of the study did not influence basal or stimulated CT levels. Basal and stimulated CT levels were significantly lower in the patients with Graves' disease than in the patients with toxic nodular goitre. We conclude that 131I used to correct hyperthyroidism may cause marked CT deficiency.     

IODINE METABOLISM IN AUTONOMOUS HOT NODULES OF THE THYROID

The thyroidal iodide clearance rate, the plasma inorganic iodine (PII), the absolute iodine uptake (AIU) by the thyroid, the serum PBI, the intrathyroidal exchangeable iodine pool, the renal iodide clearance rate and the urinary iodine excretion were measured in twenty-one cases of autonomous hot thyroid nodule with suppression of the normal parenchyma (toxic adenoma, TA), in eight cases of autonomous hot nodule without such suppression (subtoxic adenoma, STA), and in eighteen controls; the ¹³¹ I uptake and PB¹³¹ I were measured in 390 cases of TA and 111 of STA compared with eighty-one controls. The most striking finding was a greatly reduced pool of intrathyroidal exchangeable iodine in the TA group. This explained the high PB¹³¹ I values (out of proportion to the degree of hyperthyroidism) and the short biological half-life of radioiodine within the gland. There was no evidence of iodine deficiency, either from the PII or the urinary iodine measurements. Otherwise the patients with TA showed evidence of mild hyperfunction: increased ¹³¹I uptake, AIU and PBI, but with a considerable overlap with the normal range. The patients with STA had, in general, laboratory values intermediate between the TA group and the controls. The intrathyroidal exchangeable iodine pool was not significantly reduced, probably because in STA the normal parenchyma surrounding the nodule was still actively taking part in the exchange, whereas in the TA the normal parenchyma constituted a practically dormant iodine pool.     

Development of hypothyroidism during long-term follow-up of patients with toxic nodular goitre after radioiodine therapy

Objective To investigate the cure rate and incidence of hypothyroidism of radioiodine treatment with a calculated dose regimen and an intended thyroid dose of 150 Gy in patients with toxic nodular goitre during long‐term follow‐up. Patients A total of 265 consecutive patients with toxic nodular goitre were treated between March 2003 and August 2004 at our institute and followed up for a maximum of 8 years. Preliminary radioiodine testing with volumetric measurement of the thyroid by ultrasound as well as individual thyroidal radioiodine uptake and half‐life measurements were performed before radioiodine therapy. The estimated radiation dose to the thyroid was 150 Gy. Measurements Follow‐up controls with respect to success of therapy and development of hypothyroidism were performed 3 months, 1 and up to 8 years after radioiodine treatment. The relation of the achieved thyroid dose to the success rate of treatment and to the incidence of hypothyroidism was analysed. Results The cure rates were 85% at 3 months, 98% at 1 year and 98% at the end of follow‐up. Above an achieved thyroid dose of more than 120 Gy, there was no significant association between the dose achieved in the thyroid and the cure rate on follow‐up. The incidences of hypothyroidism at 3 months, at 1 year and at the end of follow‐up were 32%, 55% and 73%, respectively. Conclusions Radioiodine treatment with a calculated dose regimen is a highly effective treatment option in patients with toxic goitre with an overall success rate of 98%. However, radioiodine treatment with an intended thyroid dose of 150 Gy leads to a high incidence of hypothyroidism on long‐term follow‐up. This finding supports the suggestion that in future intended thyroid doses could be lowered in patients treated with a calculated dose regimen for toxic nodular goitre.