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.     

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.     

OUTCOME FOLLOWING STANDARDIZED 185 MBq DOSE 131I THERAPY FOR GRAVES'' DISEASE

The clinical outcome of 199 patients with Graves' disease treated with standardized 185MBq 131I therapy doses has been analysed. Most patients were controlled with antithyroid drugs prior to the 131I therapy, and also received antithyroid drugs for several months following 131I. The median follow-up period was 5.5 years. The single 185MBq 131I dose successfully treated 72.4% of patients. The 1, 2 and 5 year hypothyroid figures were 15.5%, 19.3% and 27.3%, respectively. Previous thyroidectomy was associated with an increased hypothyroid rate. Retreatment was required by 25.6%, with 3.5% requiring more than two 131I doses. Discriminant analysis of pretreatment variables suggests that patients with large goitres or severe disease (serum T3 greater than 10nmol/l) should be treated with higher doses of 131I.     

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.     

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

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

Intra-synovial 131I Human Serum Albumin (HSA) in the Investigation of Joint Disease

A procedure of radioisotope scanning using intra-synovial ¹³¹I HSA for the investigation of joint disease has been described. This has been shown to be useful in outlining cystic swellings related to joints. The most important application of the technique is the diagnosis of popliteal or calf cyst rupture which is difficult to distinguish from thrombophlebitis. Conventional radiography using phlebograms or arthro-grams has disadvantages which have not been encountered with this new technique. The radiation dose administered is not considered to be a hazard.     

小剂量^131碘治疗儿童Graves病42例疗效观察

目的 探讨小剂量^131碘(^131I)治疗儿童Graves病的疗效。方法 ^131I剂量降至常规计算用量的1／2～2／3，1次顿服，3个月为1个疗程，进行疗效复查，总剂量37～185MBq。结果 42例患儿中，痊愈38例，治愈率为90．5％；显效2例，占4．8％；无效1例，占2．4％；1例出现早发甲状腺功能低下(甲低)，经治疗后恢复。治愈总疗程1～3个，时间3～9个月。痊愈病例中，服药1个疗程治愈17人(44．8％)，2个疗程治愈16人(42．1％)，3个疗程治愈5人(13．1％)，观察3～5年，38例治愈患者中未出现甲状腺功能亢进症复发或晚发甲低。结论 小剂量^131I是治疗儿童Graves病安全、有效的方法。     

THE ASSESSMENT OF 125I TREATMENT OF THYROTOXICOSIS

257 patients have been reviewed 1-5 years (mean 3 years 2 months) after receiving one of five dose regimes of ¹²⁵I for thyrotoxicosis. The cumulative incidence of hypothyroidism was 34% and of persistent thyrotoxicosis 17%. The group receiving doses between 351 and 500 μCi/g had the highest proportion of euthyroid patients (65%) with the lowest requirement for repeat therapy (46%). In the euthyroid patients, increasing dose of ¹²⁵I was associated with progressive decline in mean thyroxine (T4) level and free thyroxine index (FTI) within the respective normal ranges, and increase in mean thyroid stimulating hormone (TSH) level to above the normal range. Euthyroid patients with elevated TSH levels had significantly lower T4 and FTI values compared with those with normal TSH, and showed a 3-4-fold increased rate of development of hypothyroidism over 1 year. Euthyroid patients with elevated T3 levels remained euthyroid during the subsequent year and mean T3 levels declined significantly, suggesting that abnormally elevated T3 levels after ¹²⁵I do not generally indicate impending relapse of thyrotoxicosis. It is concluded that the potential advantages of ¹²⁵I therapy for thyrotoxicosis in reducing the incidence of hypothyroidism have not been realized in practice.     

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.     

Preparation of 131I-Asialo-α1-Acid Glycoprotein

Abstract. α₁-Acid glycoprotein (orosomucoid) was prepared from a byproduct of the ethanol plasma fractionation by means of ion-exchange procedures. Immunoelectrophoresis suggested a high degree of purity; the purified protein contained 13.5% sialic acid and 17.8% hexose. The α₁-acid glycoprotein was modified by removal of sialic acid with neuraminidase (EC 3.2.1.18) followed by iodination with ¹³¹I. The purpose of the preparation, its potential use as a pharmacon for liver function studies in nuclear medicine is the subject of further study.     

Turnover of 131I-human spleen ferritin in plasma

Human spleen ferritin was labelled with 131I and injected into two normal men. The labelled ferritin left the plasma rapidly. The experimental clearance curve could be fitted with accuracy into two single exponential functions. The first component, T 1/2 = 9 min, accounted for the clearance of about 90% of the labelled ferritin. Surface counting showed uptake of 131I by the liver but not by the spleen. Such a rapid plasma turnover is similar to that found after injection of tissue ferritins into experimental animals but contrasts with the slow turnover previously found for 131I-labelled human plasma ferritin. Differential clearance of isoferritins from the plasma is an important factor explaining the biochemical and immunological differences between tissue and plasma ferritins.     

Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with 131I-meta-iodobenzylguanidine (131I-mIBG)

OBJECTIVE: Meta-iodo-benzyl-guanidine labelled with 131-iodine [(131)I-mIBG] has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non-catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of (131)I-mIBG, we have reviewed all patients who had received this form of treatment in our department. DESIGN: Retrospective analysis of the case notes of patients with neuroendocrine tumours who received treatment with (131)I-mIBG and were followed-up according to a defined protocol in a given time frame. PATIENTS: Thirty-seven patients (18 with metastatic carcinoid tumours, 8 metastatic phaeochromocytoma, 7 metastatic paraganglioma and 4 metastatic medullary carcinoma of the thyroid) treated with (131)I-mIBG over a 15-year period were included in this analysis. MEASUREMENTS: The symptomatic, hormonal and tumoural responses before and after (131)I-mIBG therapy over a median follow-up duration of 32 months (range 5-180 months) were recorded. Of the 37 patients (22 males; median age 51 years, range 18-81 years), 15 were treated with (131)I-mIBG alone whereas the other 22 received additional therapy. RESULTS: A total of 116 therapeutic (131)I-mIBG doses were administered [mean cumulative dose 592 mCi (21.9 GBq); range 200-1592 mCi (7.4-58.9 GBq)]. None of the patients showed a complete tumour response. However, 82% of patients treated with (131)I-mIBG alone and 84% who received additional therapy showed stable disease over the period of follow-up. Overall survival during the period of the study was 71%. The overall 5-year survival rate was 85% (95% confidence interval, 72-99%) for all patients and 78% (95% confidence interval, 55-100%) for the carcinoid group alone, according to Kaplan-Meier analysis. Symptomatic control was achieved in all the patients treated with (131)I-mIBG alone, and in 72% of those receiving additional therapy. Hormonal control was noted in 50% and 57% of patients, respectively. (131)I-mIBG therapy was safe and well tolerated. Serious side-effects necessitating the termination of (131)I-mIBG therapy were seen in only 2 of our patients. CONCLUSIONS: (131)I-mIBG therapy produces symptomatic and hormonal improvement and moderate tumour regression/stabilization in patients with metastatic neuroendocrine tumours with minimal adverse effects. It may be a valuable alternative or additional therapeutic option to the currently available conventional treatment modalities.     

Iron Absorption, Iron Loss and Iron Retention in Man: Studies after Oral Administration of a Tracer Dose of 59FeSO4 and 131BaSO4

The absorption of iron administered as ferrosulphate was studied in normal subjects, in patients with iron deficiency and in patients with idiopathic and secondary haemosiderosis. By using a test dose combining radioactive iron (⁵⁹Fe) with radioactive barium sulphate (¹³¹Ba) as inert indicator, it was possible to determine how much iron was initially absorbed and whether a proportion of this was later excreted in the faeces.
The (initial) iron absorption, the iron loss as a percentage of the iron absorbed, and the (ultimate) iron retention 2 weeks after administration of the test dose were calculated.
In normal subjects and patients with secondary haemosiderosis, a large proportion of the initially absorbed iron later returned to the intestinal lumen. In patients with iron deficiency and those with idiopathic haemosiderosis, however, nearly all the initially absorbed iron was retained in the organism. In differential diagnosis between idiopathic and secondary haemosiderosis, therefore, determination of the iron absorption and iron retention percentages from a test dose may be important.
In patients with secondary haemosiderosis there seemed to be a negative correlation between the degree of haemosiderosis and the amount of iron from the test dose ultimately retained in the organism.     

Studies on Circulating Soluble Fibrin: Separation of 125I-Des-AB Fibrin and 131I-Fibrinogen by Gel Filtration

The behaviour of labelled des-AB fibrin in plasma was studied by gel filtration after it had been injected into rabbits. Purified rabbit [125I]des-AB fibrin was prepared by clotting of [125I]fibrinogen by thrombin and solubilizing the formed clot in buffered 3 M urea. Gel filtration of this material on urea-equilibrated columns showed a single peak identical to the elution profile of fibrinogen. This indicated the existence of monomeric des-AB fibrin. When plasma from rabbits injected with monomeric [125I]des-AB fibrin and [131I]fibrinogen was gel-filtered through plasma-equibrated columns, two separate peaks of radioactivities were obtained. The first peak eluted mainly with the void volume and contained [125I]des-AB fibrin whereas the second peak eluting within the fractionation range contained [131I]fibrinogen. Identical elution profiles were obtained in in vitro studies when monomeric [125I]des-AB fibrin was mixed with plasma containing [131I]fibrinogen and gel-filtered through plasma-equilibrated columns. We conclude from these studies that monomeric des-AB fibrin formed high-molecular weight aggregates or changed its conformation posing as a larger molecule than fibrinogen when injected into rabbits. No complex formation between des-AB fibrin and fibrinogen was observed as [131I]fibrinogen was not incorporated into des-AB fibrin aggregates. Thus, soluble des-AB fibrin can circulate in the blood without forming fibrin-fibrinogen complexes.     

Thyroid function after resection for non-toxic goitre with special reference to thyroid lymphocytic aggregation and circulating thyroid autoantibodies

A series of 91 patients operated on for non-toxic goitre was followed systematically during 24 months post-operatively with regard to thyroid function. A thyroid remnant of at least 5 to 8 g was left in the majority of cases, and thyroid replacement was not given. Histopathological grading was performed on goitrous specimens with reference to lymphocytic infiltration. Thyroglobulin antibodies and thyroid microsomal antibodies were determined pre-operatively. Goitre resection provoked a high, but transient increase in serum thyroid stimulating hormone (TSH) levels with peak values 3 to 6 months after operation. Twenty-four months after surgery serum TSH values had normalized, but were still slightly elevated in patients with bilateral surgery and high lymphocytic infiltration, 9% of the patients. The concentration of serum free thyroxine index (FT4I) and serum total triiodothyronine (TT3) decreased after operation, but within reference range. Twenty-four months after surgery, serum FT4I was back to baseline values, while serum TT3 was still lowered compared to the pre-operative level. None of the patients developed overt hypothyroidism. Occurrence of circulating thyroid autoantibodies was not related to post-operative changes in thyroid parameters. We conclude that thyroid replacement therapy seems not to be indicated routinely following resection for non-toxic goitre, but precaution should be taken in case of bilateral resection and high lymphocytic infiltration of goitrous specimens.