Radioiodine therapy for multinodular toxic goiter.

BACKGROUND: Radiolabeled iodine 131 therapy is used for treatment of multinodular toxic goiter, but long-term follow-up studies are lacking. METHODS: A prospective study of 130 consecutive patients (115 women) treated with 131I for multinodular toxic goiter and followed by evaluation of thyroid volume (determined using ultrasound) and thyroid function variables. RESULTS: The patients were observed for a median of 72 months (range, 12-180 months). Sixty-six patients received antithyroid drug pretreatment; 64 did not. Iodine 131 treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-hour 131I uptake) was given as a single dose in 81 patients, 2 doses in 38, and 3 to 5 doses in 11. One or 2 treatments cured 119 patients (92%), and 68 (52%) became euthyroid within 3 months after 131I treatment. The median 131I dose was 370 MBq (range, 93-1850 MBq). Forty-nine patients needing more than 131I dose had a reduction in median thyroid volume from 56 mL (range, 21-430 mL) to 44 mL (range, 15-108 mL), representing a 24% reduction related to the insufficient 131I dose. In all patients, the initial median thyroid volume of 44 mL (range, 16-430 mL) decreased to 25 mL (range, 8-120 mL) (P<.005), representing a median reduction of 43%, 24 months after the last 131I dose. Hypothyroidism evaluated using life-table analysis developed in 6% of patients who did not receive antithyroid pretreatment and 20% who did (P<.005) after a median of 42 months (range, 3-60 months), the total hypothyroidism frequency being 14% within 5 years of treatment. CONCLUSIONS: Ninety-two percent of patients with multinodular toxic goiter were cured with 1 or 2 treatments. The thyroid volume was reduced by 43%, with few side effects. Iodine 131 should be the choice of treatment in patients with multinodular toxic goiter.     

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.     

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 volume and function after 131I treatment of diffuse non-toxic goitre

OBJECTIVE Traditional treatment modalities of diffuse non-toxic goitre are thyroid hormone suppression or surgery. When treating nodular non-toxic goitre with ¹³¹I treatment a reduction in thyroid volume to about 50% has been observed. In the present study we evaluated the effect of ¹³¹I treatment of diffuse non-toxic goitre. DESIGN Retrospective study of patients treated for a diffuse non-toxic goitre and followed by evaluation of thyroid volume measured by ultrasound. PATIENTS Ten selected patients from our out-patient clinic with diffuse non-toxic goitre. MEASUREMENTS Thyroid volume was measured by ultrasound and thyroid function by serum values of T4, T3, T3 uptake ratio, TSH, TSH receptor antibodies and thyroid peroxidase antibodies (anti-TPO). Measurements were performed before and 1, 3, 6 and 12 months (and 18 months (n=7), thyroid volume measured in six patients)) after ¹³¹I treatment. RESULTS Thyroid volume declined in all patients from median 41 (range 27–160) ml to 20 (range 9–108) ml over 1 year, a reduction of 47%. One patient developed transient and one persistent hypothyroidism in the follow-up period. Both had elevated anti-TPO levels before treatment (331 and 9185 U/ml) and demonstrated titre increases of 2.5 and 30 times after 3 and 6 months, respectively. Pretreatment values were reached after 1 year. The other eight patients had normal anti-TPO levels and free T4 and T3 indices did not change during follow-up, whereas serum TSH levels demonstrated upward trends within the normal range (P<0.05). TSH receptor antibodies were normal and remained so in all patients. CONCLUSION S¹³¹I treatment of diffuse non-toxic goitre reduces thyroid volume by approximately 50% within 12–18 months. Hypothyroidism, during a limited follow-up period, developed only in patients with positive anti-TPO levels before treatment.     

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.     

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.     

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.     

Determinants of longterm outcome of radioiodine therapy of sporadic non-toxic goitre

OBJECTIVE: Radioiodine treatment is effective in reducing the size of sporadic nontoxic goitre, albeit at the expense of a high incidence of postradiation hypothyroidism. The decrease in goitre size, however, is not observed in all subjects, and little is known about recurrent goitre growth after 131I therapy. The aim of the present study was to evaluate which factors determine the longterm outcome of 131I treatment in patients with sporadic nontoxic nodular goitre, in terms of changes in both thyroid size and thyroid function. STUDY DESIGN: Retrospective follow-up study. PATIENTS: Fifty patients with sporadic nontoxic nodular goitre were evaluated who had been treated in our institution with 131I (mean dose 4.4 MBq/g thyroid) in the period 1988-95. Nine patients received a second dose of 131I and one a third. Median follow-up time was 41 months (range 24-115). MEASUREMENTS: Thyroid function was assesed by TSH and FT4 index, and thyroid volume by ultrasound in 46 patients, by scintiscan using the Himanka formula in three and by CT-scan in one. The response to treatment was defined as a decrease in thyroid volume of greater than 13% (i.e. the mean + 2SD of the coefficient of variation of volume measurements), and recurrent goitre as an increase in thyroid volume greater than 13% after an initial response. RESULTS: Goitre size decreased from a median value of 82 ml (range 17-325) to 37 ml (range 6-204) two years after 131I treatment, a median reduction of 49%. The decrease in goitre size was directly related to the dose of 131I (r = 0.50, P = 0.0003) and indirectly to baseline goitre size (r = - 0.35, P = 0.006). Seven patients (14%) were nonresponders, and four (8%) experienced recurrent goitre growth after 3-5 years. These 11 patients (22%) when compared to the remaining 39 responders (78%) had larger goitres with more often a dominant nodule, and had received a lower 131I dose. The efficacy of a second dose of 131I (median reduction in goitre size 37%) was comparable to the first dose. Hypothyroidism occurred in 24 patients (48%), mostly in the first two years after treatment; 11 had overt and 13 subclinical hypothyroidism. Kaplan Meier statistics indicated a probability of 58% for developing hypothyroidism after 8 years. Hypothyroid patients had a smaller initial goitre size and a higher prevalence of TPO antibodies and a family history of thyroid disease than the patients who remained euthyroid; the 131I dose did not differ between the two groups. CONCLUSIONS: The size of sporadic nontoxic goitres is reduced on average by 50% after a single dose of 4.77 MBq 131I/g thyroid. Independent determinants of the relative decrease in thyroid volume are administered 131I dose and initial goitre size. Nonresponders (14%) and those with late recurrence of goitre growth (8%) have larger goitres and more often dominant nodules than responders. Determinants of postradioiodine hypothyroidism (cumulative risk 58% after 8 years) are the presence of TPO antibodies, a family history of thyroid disease and a relatively small goitre.The implications of these findings are that the efficacy of a given 131I dose can be enhanced when administered at an earlier stage when the goitre is still smaller, albeit at the expense of an increased risk for developing hypothyroidism.     

Stimulation with 0.3-mg recombinant human thyrotropin prior to iodine 131 therapy to improve the size reduction of benign nontoxic nodular goiter: a prospective randomized double-blind trial

BACKGROUND: Use of recombinant human thyrotropin increases the thyroid radioiodine (iodine 131 [(131)I]) uptake and may have a role in the context of (131)I therapy of benign goiter. METHODS: In a double-blind, placebo-controlled trial, 57 patients with nodular nontoxic goiter (51 women and 6 men) were randomized to receive either 0.3 mg of recombinant human thyrotropin (n = 28) or placebo (n = 29) 24 hours before (131)I therapy. The (131)I dose was calculated based on thyroid size (measured by ultrasound), thyroid (131)I uptake, and (131)I half-life. The follow-up period was 1 year and included measurements of thyroid size and function and patient satisfaction. RESULTS: Baseline median goiter volume was 51 mL (range, 20-99 mL) in the placebo group and 59 mL (range, 25-92 mL) in the thyrotropin group (P = .75). At 12 months, the mean +/- SEM relative goiter reduction was 46.1% +/- 4.0% in the placebo group and 62.1% +/- 3.0% in the thyrotropin group (P = .002 between groups). The difference was most pronounced among patients with large goiters. Within each group, there was no significant correlation between retained thyroid (131)I dose and goiter reduction. Adverse effects were significantly more frequent in the thyrotropin group (34 vs 12 events; P<.001). Permanent hypothyroidism developed in 3 patients (11%) in the placebo group compared with 16 patients (62%) in the thyrotropin group (P<.001). Patient satisfaction was high and uninfluenced by the use of recombinant human thyrotropin. CONCLUSIONS: Stimulation with recombinant human thyrotropin prior to (131)I therapy improves thyroid size reduction by 35%, with a 5-fold higher rate of hypothyroidism. These effects are, at least partially, mediated through mechanisms other than an increase in retained (131)I thyroid dose. Further recombinant human thyrotropin dose-finding studies are warranted before routine use.     

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.     

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.     

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.     

Chronic myeloid leukaemia following 131I treatment for thyroid carcinoma: a report of two cases and review of the literature

Leukaemia is an uncommon late complication of exposure to the Ionizing radiation of radioactive Iodine (¹³¹I). Most cases reported have been of acute ieukaemias developing after high doses of ¹³¹I. Only a few cases of chronic myeloid leukaemia (CML) have been reported in this setting to date. We report two new cases of CML after low dose radioactive iodine and review the literature. We present an analysis of the minimal relative risk of CML developing in thyroid cancer patients treated with ¹³¹I in Israel. Two male patients, 35 and 51 years old, developed CML following low dose ¹³¹I therapy for metastatic mixed papillary and follicular carcinoma of the thyroid. Both had undergone thyroidectomy and neck dissection and thyroid ablation with ¹³¹I (total dose: 56 and 130 mCl respectively). Four and 10 years later, respectively, a leucocytosis was noticed with typical blood smears, and CML was diagnosed either by Philadelphia translocation or bcr-abl gene rearrangement. Thyroid cancer at that time was in remission. Estimated minimal relative risk of CML after ¹³¹I therapy where the population considered at risk comprised all thyroid cancer patients detected during the years 1981–1991 in Israel was 8.95 (95% confidence limits 2.26–35.16). Literature review disclosed five additional similar cases. The mean radioiodine dose given to the seven CML patients was 11416 MBq (range 1134–32130 MBq), considerably lower than the dose given to patients reported in the literature who subsequently developed acute leukaemias (mean 34965, range 3856–54810 MBq). We suggest that CML is a potential complication of low dose ¹³¹I therapy given for thyroid carcinoma even at the lower end of the dose range used for this indication. Leucocytosis appearing in these patients should raise the suspicion of secondary CML.     

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.     

Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer.

We have compared the dose of levothyroxine (L-T4) required to suppress serum TSH to given levels in two clinical groups: 1) 44 patients with thyroid cancer whose thyroid glands had been ablated by surgical thyroidectomy and 131I treatment, and 2) 113 patients with thyroidal failure due either to spontaneous primary hypothyroidism (31 patients) or after 131I treatment for Graves' hyperthyroidism (82 patients). The dose of L-T4 needed to attain serum TSH levels in the euthyroid range (0.5-6.2 microU/mL) was significantly greater (P less than 0.01) in patients with thyroid cancer (2.11 micrograms/kg.day) than in the patients with primary hypothyroidism associated with nonmalignant disease (1.63 micrograms/kg.day). Similarly, patients with thyroid cancer required a higher dose of L-T4 to suppress serum TSH to a given subnormal level. These findings suggest that the secretion of hormone from residual thyroid tissue in patients who have not been subjected to near-total thyroid ablation contributes substantially to the circulating levels of serum T4 and T3. We, therefore, infer that residual thyroidal secretion in the patients with hypothyroidism due to benign causes is relatively independent of TSH stimulation. Further subdivision of patients with benign hypothyroidism revealed that patients with Graves' who developed hypothyroidism after 131I treatment showed a lower mean dose requirement than patients with spontaneous hypothyroidism. This raises the possibility that continued secretion of thyroid-stimulating immunoglobulin in such patients might account for the lower dose requirement in the combined group with hypothyroidism. Our studies also have allowed us to make serial observations in 4 patients with thyroid cancer who exhibited elevated levels of serum thyroglobulin. In this limited series, maximal suppression of serum thyroglobulin was produced by doses of L-T4, which reduced circulating TSH to 0.4 mU/L.     

Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre

A patient with toxic nodular goitre is described in whom radioiodine (¹³¹I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse ¹³¹I uptake by the gland. A second administration of ¹³¹I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH-receptor antibody and thyroid stimulating antibody were undetectable before ¹³¹I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of ¹³¹I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH-receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH-receptor, thus turning a toxic nodular goitre into Graves' disease.     

Compensated 131I-therapy of solitary autonomous thyroid nodules: effect on thyroid size and early hypothyroidism

Thyroid function and thyroid gland volume, ultrasonically determined, were investigated in 27 hyperthyroid patients with solitary autonomous thyroid nodules before and during one year after 131I-treatment. Total thyroid volume decreased gradually from 40.9 +/- 3.5 ml (mean +/- SEM) before treatment to 23.9 +/- 1.8 ml (P less than 0.001) at 3 months after 131I-treatment. No further change was observed. All but two patients received only one dose of 131I, and in spite of a significant decrease also of the non-adenoma side of the gland, none became hypothyroid. We conclude that 131I-therapy has an important place in the treatment of solitary autonomous thyroid nodules since all our patients became euthyroid within 3 months, only 2 of 27 patients needed more than one dose of 131I, no cases of hypothyroidism occurred, and thyroid volume was substantially decreased.     

Radioactive iodine for hyperthyroidism in children and adolescents: referral rate and response to treatment

Objectives Radioactive iodine (¹³¹I) therapy is increasingly viewed as a safe and effective treatment for paediatric and adolescent hyperthyroidism. Our objective was to estimate treatment response and its predictors and describe current referral practices for ¹³¹I therapy. Design Retrospective study. Patients One hundred and thirty‐one children 30 days–21 years old with laboratory evidence of hyperthyroidism, seen in an academic paediatric and adolescent endocrinology practice. Measurements Rate of referral, indications for ¹³¹I, predictors of poor treatment response. Results Thirty‐eight of 102 patients with persistent hyperthyroidism (37%) received ¹³¹I (160 μCi/g thyroid tissue/¹³¹I uptake), as did an additional 10 patients initially evaluated by adult thyroidologists. Primary indications were intolerance to (29%) or poor control on (19%) antithyroid drugs, patient preference (50%) and unknown (2%). Of 48 patients treated with ¹³¹I, 89% and 11% became hypothyroid after one and two ¹³¹I doses, respectively. The goal of ¹³¹I therapy was attainment of hypothyroidism. ‘Poor treatment response’ (seen in 27%) was defined as requirement for a second ¹³¹I dose or failure to achieve hypothyroidism after 6 months. Predictors of poor treatment response included: previous use of antithyroid drugs (37%vs. 0%, P = 0·02), ophthalmopathy (58%vs. 8%, P = 0·002), and an interval of ≥12 months from diagnosis to ¹³¹I (50%vs. 10%, P = 0·003). A very elevated free T4 tended to be more prevalent in those with poor response. Conclusions In children and adolescents with hyperthyroidism, high rates of success after ¹³¹I are achievable. Use of antithyroid drugs, pre‐existing eye disease and prolonged time to ¹³¹I may confer relative resistance to ¹³¹I.     

Acute pre-tibial myxoedema following radioiodine therapy for thyrotoxic Graves' disease

A 54-year-old woman was treated with an oral dose of S55MBq of ¹³¹I radioiodine for thyrotoxicosis. She had no clinically detectable extrathyroidal manifestations of Graves' disease at the time, but within two months developed moderately severe ophthalmopathy and very extensive thyroid dermopathy affecting her face, arms, hands and feet, in addition to the classic pre-tlblal area. Although she developed mild post radioiodine hypothyroidism, this was detected at an early stage and its treatment had no effect on the extrathyroldal signs. Thyrotrophin receptor antibodies (TRAb) were positive before treatment (22% Inhibition of T S H binding in neat serum), rose to very high levels following radioiodine (97.6% Inhibition), and fell progressively over the following year during treatment with prednisolone. Thyroglobulln autoantibodies became detectable following radioiodine but thyroid peroxidase antibodies were undetectable throughout. Serum and purified IgG from blood samples obtained prior to steroid therapy and over the subsequent year were tested on a dermal fibroblast cell line in vitro for the stimulation of synthesis of glycosamlnoglycans, protein and DNA, but no increase in radiolabel incorporation was apparent for any sample when compared to controls. The temporal relation between the radioiodine and the acute onset of dermopathy and ophthalmopathy, together with the abrupt rise in TRAbs, indicates a probable causal association. However, the absence of In-vitro fibroblast stimulation would suggest that the pathogenesis of Graves' dermopathy is not dependent solely on any simple humoral factor.