Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy

Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.     

Marine-Lenhart syndrome: a case observation upon 18 years

After a hyperthyroidism of Graves' disease with strongly positive antithyroid antibodies treated sufficiently by radioiodine therapy a 46-year old woman developed a consecutive bifocal autonomous nodule within 13 years. This phenomenon is known as Marine-Lenhart-syndrome. In this particular case it seems that autonomous nodules are a consequence of Graves' disease treatment with radioiodine. Our case report is a 18 year follow up. In contrast to most studies known today the simultaneous occurrence of active Graves' disease and active autonomous nodules could be demonstrated by means of serology and suppressive scintigraphy, respectively. In addition, this case shows the possible dependence of an acute beginning of Graves' disease and the occurrence of autonomous nodules.     

Dosimetry study in patients with autonomous thyroid nodule who are candidates for radioiodine therapy.

A dosimetry study was performed on 26 patients with an autonomous thyroid nodule and suppressed serum thyroid-stimulating hormone, to determine the dose to extranodular tissue when the nodule receives 300 Gy for 131I therapy. METHODS: Parameters of radioiodine turnover to be used in the dosimetry formula were separately obtained for the nodule and the contralateral lobe, as a measurable example of the extranodular tissue, using 55 MBq 123I and a computer-assisted gamma camera. The biologic half-life of 123I was then converted into the effective half-life of 131I, and the volumes of the nodule and the lobe were obtained by scintigraphy or sonography. RESULTS: The mean dose to the contralateral lobe from uptake and irradiation by the nodule was calculated to be 32 Gy, and that to the ipsilateral lobe was estimated to be 34 Gy. CONCLUSION: During radioiodine therapy for autonomous thyroid nodules, the extranodular tissue receives a higher dose than is generally assumed, which explains the relatively high rate of post-treatment hypothyroidism reported in the literature.     

131Ⅰ治疗非Graves'甲状腺功能亢进及非毒性甲状腺肿后诱发Graves'病

~(131)I治疗非Graves’甲亢及非毒性甲状腺肿后数月,少部分患者体内出现促甲状腺激素受体抗体并诱发Graves’病(GD),发病率在0．05%～5%之间。其发病机制假说有通过自身免疫反应介导等。通过监测体内甲状腺自身抗体水平变化、甲状腺显像,可以预测~(131)I治疗后GD的发生。其治疗方法有抗甲状腺药物治疗、再次放射性~(131)I治疗、手术治疗。     

Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) may be caused by excessive thyroidal hormone synthesis and release (type 1) or by a destructive process (type 2). This differentiation is considered essential for therapeutic choice. PURPOSE: To evaluate the utility of color-flow Doppler sonography (CFDS) in the differential diagnosis and management of AIT. MATERIAL AND METHODS: The clinical and laboratory data, thyroid sonography (grayscale sonography [GSS], CFDS), thyroid radioiodine uptake (RAIU) and thyroid scintigraphy, treatment, and clinical outcome were retrospectively reviewed in 21 AIT patients. The CFDS pattern of thyroid nodules was separately described from that of the perinodular parenchyma, and AIT was classified as type 1 (increased blood flow) or type 2 (low/no blood flow). Type 1 AIT patients were treated with methimazole (alone or associated with potassium perchlorate), while type 2 patients were treated with prednisone or amiodarone withdrawal alone. RESULTS: Eleven patients with increased blood flow were considered as type 1, and 10 with low/no blood flow as type 2. Ten of the 11 patients in the first group showed a hypervascular nodular pattern, while one showed a hypervascular parenchymal pattern. Clinical diagnoses were toxic nodular goiter and Graves' disease, respectively. Of the 10 patients with low/no blood flow, six had normal thyroid volume, three small diffuse goiter, and one small multinodular goiter. The clinical outcome showed that 20 of the 21 patients were treatment responsive. CONCLUSION: CFDS is a useful tool in the differential diagnosis of AIT. This differentiation appeared to be of clinical relevance as regards therapeutic choice. Separate evaluation of parenchymal blood flow from that of nodules may prove beneficial in the diagnosis of underlying thyroid diseases in patients with type 1 AIT.     

Evaluation of dosimetry of radioiodine therapy in benign and malignant thyroid disorders by means of iodine-124 and PET

The aim of this study was to evaluate the use of 124I positron emission tomography (PET) to determine the dosimetry of radioiodine therapy in hyperthyroidism and thyroid cancer. Phantom studies to assess the accuracy of PET were performed using an EEC phantom with spheres of different diameters filled with 3-30 MBq of 124I. Patient dosimetry was derived from PET data obtained 1-13 days after simultaneous oral administration of a therapeutic dose of 131I and a diagnostic dose of 124I. The obtained data were compared with findings from intratherapeutic probe measurements and clinical outcome. The phantom studies confirmed that 124I can be quantitated by PET (imprecision < or =10%), and volumetry is feasible for nodules <13 mm (imprecision < or =20%). Any influence of contamination with 123I or the simultaneous administration of 131I on the accuracy of the PET quantification and the probe measurements was ruled out by phantom measurements with solutions of 131I, 124I and 123I in various ratios. In autonomous nodular goitres, radioiodine uptake measured by PET varied from 25.4% to 64.3% and was not significantly different from that obtained by a scintillation probe (24.1%-73.1%, correlation coefficient r=0.91). Comparison of uptake and effective half-life in normal tissue versus autonomous nodules revealed significant differences in uptake but not in effective half-life [uptake 2.0-8.3 kBq/(ml x MBq) in normal tissue vs 12.6-29.3 kBq/(ml x MBq) in nodules; half-life 97.8-156.7 h in normal tissue vs 73.3-192.3 h in nodules]. Calculated radiation doses ranged between 177 and 633 Gy for autonomous nodules and between 47 and 126 Gy for normal tissue. In thyroid cancer patients, doses between 350 and 1,420 Gy were achieved in thyroid remnants and between 70 and 170 Gy in tumour metastases. It is concluded that 124I and PET are suitable for evaluation of the dosimetry of radioiodine therapy in benign and malignant thyroid diseases. The applied technique might be particularly useful for quantitative dose-response studies in radioiodine treatment and further investigations of stunning phenomena.     

Thyroid cancer prevalence after radioiodine treatment of hyperthyroidism.

The definitive treatment of hyperthyroidism in Europe is quite different from that in the United States. In Europe, the surgical approach is often preferred and considered safer than radioiodine treatment. European doctors usually prefer to surgically remove the thyroid and perform a pathologic examination of it. They consider it to be an essential diagnostic tool to identify possible diseases that might be associated with hyperthyroidism and even to detect the rare thyroid tumors that might be associated with thyroid hyperfunction. The aim of this study was to evaluate whether radioiodine therapy could be a risk factor for the misdiagnosis of thyroid cancer. METHODS: We performed a retrospective revision of data we collected from 6647 patients (1171 [17.5%] men, 5476 [82.5%] women), all of whom underwent 1311 therapy for hyperthyroidism from 1970 to 1997. Of the whole group, 6.5% were younger than 40 y, 33.5% were 40-60 y old, and 60% were older than 60 y. Moreover, 5061 (76%) patients had either an autonomously functioning node or a toxic multinodular goiter. The other 1586 (24%) patients had Graves' disease. RESULTS: After treatment, thyroid cancer was discovered in 10 (0.15%) patients, none of whom belonged to the group of patients with Graves' disease. Five of these patients were treated during a period from 1970 to 1980, when sonography was not routinely available. The incidence of thyroid cancer in the series of radioiodine-treated patients (150/100,000 over a 27-y period) was not significantly different from its incidence in the general population. The expected rate is 124.88 per 100,000 over a 27-y period. CONCLUSION: An accurate preliminary evaluation (clinical examination, sonography, and cytologic evaluation of fine-needle aspiration) is fundamental for a proper choice between radioiodine and surgical therapy.     

The role of imaging in Graves' disease: a cost-effectiveness analysis

According to many guidelines, scintigraphy remains the first suggested diagnostic procedure in hyperthyroid patients in spite of the widespread availability of ultrasounds. The aim of this study was to evaluate the cost-effectiveness of sonography versus scintigraphy in the management of Graves's disease, and to assess ultrasound features suggesting cancer in detecting thyroid nodules. Among 1470 hyperthyroid patients evaluated in our department from 2002 to 2005, 426 (29%) had Graves' disease: echographic and scintigraphic features were not suggestive of GD in 20/426 (4.8%) and 11/426 (2.6%) patients, respectively (p=0.763), even if one of the two procedures was almost always diagnostic. Ultrasound identified 68/426 (16%) patients with a concomitant solid lesion, while scintigraphy detected only 9/426 (2.1%) "cold" nodules (p<0.001). Thyroid cancer was diagnosed in 30/68 (47.7%) patients. Malignancy presented at ultrasound investigation blurred margins (26.7% versus 15.8%), microcalcifications (33.3% versus 28.9%) and an anteroposterior and transverse diameter ratio>or=1 (73.3% versus 71.1%); more frequently than benign nodules, but this was not statistically significant. The total cost to obtain a diagnosis by ultrasound was euro14645.34 (euro13312.5 for echography+euro1332.84 for scintigraphy in the 29 patients "negative" at echographic evaluation for GD) versus euro19922.71 by scintigraphy (euro19578.96 for scan+euro343.75 for ultrasounds in the 11 patients "negative" at scintigraphy). Our data show no difference in terms of diagnosis between sonography and scintigraphy. Indeed, scintigraphy was less sensitive in detecting nodules (often of malignant nature) than ultrasound, and, moreover, with a consequent increase of the direct cost of nodule management when scintigraphy is the first line procedure. In conclusion, according to our results, we suggest that ultrasounds with color-Doppler evaluation should be performed as first step in all hyperthyroid patients, and that scintigraphic examination should be limited only to the uncommon cases, where physician's observation, laboratory assays and/or ultrasounds are not diagnostic.     

Scintigraphic patterns in patients with subclinical hyperthyroidism

The occurrence of suppressed thyroid stimulating hormone (TSH) levels in the presence of normal free thyroxine (fT4) and free triiodothyronine (fT3) is not rare. Although this entity may be defined as "subclinical hyperthyroidism", many patients presented with the above laboratory findings, suffer from non-specific signs and symptoms that could be related to hyperthyroidism. The aim of this study was to evaluate this entity using the standard method of radionuclide thyroid imaging by (99m)Tc-pertechnetate ((99m)TcO(4)(-)). Fifty-two patients (18 males; mean age: 45+/-9 years and 34 females; mean age: 43+/-11 years) with suppressed serum TSH levels and normal fT3 and fT4 levels, who were referred to our nuclear medicine department for thyroid scintigraphy were prospectively included in the study. Any thyroidal or non-thyroidal medication, thyroid surgery or non-thyroidal diseases constituted the main exclusion criteria. Thyroid scintigraphy was performed 15 min after the i.v. injection of 111 MBq (99m)TcO(4)(-) using a pinhole collimator. Scintigraphic findings were visually evaluated. All patients had normal serum levels of fT4 (mean value 1.53+/-0.14 ng/dl, normal range: 0.89-1.8 ng/dl) and fT3 (mean value 3.9+/-0.17 ng/dl, normal range: 2.3-4.2 ng/dl). Mean value of serum TSH levels was 0.09+/-0.12 microIU/ml (normal range: 0.35-5.5 microIU/ml). The above hormones were tested by the chemiluminescent method. Patients showed seven different scintigraphic patterns in their thyroid scintigrams as follows: hyperactive+hypoactive multinodular goiters, 27%; hyperactive multinodular goiters, 23%; hypoactive multinodular goiters, 15%; solitary hypoactive nodular glands, 14%; normal glands, 9%; solitary hyperactive nodular glands, 8%; and diffuse hyperactive glands, 4%. All but two patients (50/52 = 96%) showed mild to moderate hyperplasia of the thyroid gland. It is concluded that most patients with subclinical hyperthyroidism, (96%) show mild to moderate hyperplasia of the thyroid, and many (65%) show multinodularity with at least one hyperactive nodule.     

Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake

The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)). The TcTU(s) value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70+/-9 years, and the mean thyroid volume was 54+/-26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU(s): 150 Gy for a TcTU(s) of 1.5%-2.49%, 200 Gy for a TcTU(s) of 2.5%-3.49%, 250 Gy for a TcTU(s) of 3.5%-4.49% and 300 Gy for a TcTU(s) of > or =4.5%. Normalisation of TcTU(s) and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU(s) in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54+/-26 before treatment to 34+/-20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU(s) can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism.     

Radiologische und nuklearmedizinische Diagnostik und Therapie der Schilddrüsenerkrankungen

Malignant thyroid diseases have increased in recent years. The distinction between differentiated and non-differentiated thyroid carcinoma is essential for therapy and follow-up. The frequently diagnosed papillary and follicular thyroid carcinomas are differentiated and have a good prognosis. Clinical symptoms are relatively unspecific, however imaging and laboratory testing can often provide evidence for diagnosis of thyroid carcinoma. Therapy typically involves surgery, ablative radioiodine therapy and subsequent suppressive hormone substitution. The pillars of follow-up are diagnostic scintigraphy, sonography and laboratory tests. Redifferentiation or a change of the tracer can make dedifferentiated tumors again susceptible to nuclide therapy. New treatment options have become available with the introduction of tyrosine kinase inhibitors.     

核素显像和B超测算甲状腺重量的对比研究

对照研究核素显像和Ｂ超测算甲状腺重量的相关性，为临床提供较准确及简易的方法。３６３例甲亢病人１３１Ｉ治疗前分别进行γ显像和Ｂ超检查，以测算甲状腺体积（重量），其中６５例弥漫性甲状腺肿合并甲亢病人１３１Ｉ治疗后６个月重复两种检查。３６３例病人显像和Ｂ超测算甲状腺重量相关良好（ｒ＝０９３，Ｐ＜００１），总体上显像所得重量平均值大于Ｂ超值，腺体厚度是影响测算结果的主要因素；１３１Ｉ治疗后腺体厚度缩小最著，显像值大于Ｂ超值更明显。甲状腺重量测算在一定范围内两种方法可互相替代。１３１Ｉ治疗后，Ｂ超测定值为准。存在结节时，以显像为优。     

Scintigraphy with 99mTc-pertechnetate in the evaluation of functional thyroidal autonomy.

Iodine deficiency and iodine deficiency disorders are still present in several parts of Europe. Sonography is neither specific in the diagnosis nor sensitive in the evaluation of the amount of autonomous thyroid tissue. Thyroidal autonomy is defined as a functional state of the thyroid and therefore only functional scintigraphic imaging, preferably performed with 99mTc-pertechnetate (99mTcO4-), will offer both high sensitivity and specificity in its diagnosis. Recently the cloning and characterisation of the Na+/I- symporter (NIS) offered a deeper understanding of iodine and pertechnetate uptake in the thyroid gland. Overexpression of the Na+/I- symporter following activation of the adenylate-cyclase-cAMP-cascade has been demonstrated in hot nodules, which gives for the first time an explanation for the enhanced iodine clearance of autonomous thyroidal tissue on a molecular level. The scintigraphic evaluation of thyroidal autonomy is performed both as a quantitative and qualitative thyroid scintigraphy, using a gamma camera fitted with an on-line computer system. A strong and linear correlation between the global 99mTc-pertechnetate thyroid uptake (TCTU) and 123I clearance has been recognised. Therefore TCTU-values can be used as a reliable equivalent of the iodine clearance in the evaluation of actual thyroid function. The clinical value of the TCTU in the diagnosis of thyroidal autonomy is limited because it represents iodine clearance of both normal and autonomous tissue. As a consequence scintigraphic diagnosis and quantification of autonomy can only be established if the global 99mTc-pertechnetate thyroid uptake under suppression (TCTUs) is determined. This method is sensitive in risk stratification of spontaneous or iodine induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy independently of its distribution and in the evaluation of therapeutic success after definitive therapy.     

Is thyroid scintigraphy necessary before I-131 therapy for hyperthyroidism? Concise communication

To assess the value of routine thyroid scintigraphy in the differential diagnosis of hyperthyroidism and as a guide to I-131 therapy, we prospectively examined 100 consecutive hyperthyroid patients referred for a 24-hr radioiodine uptake and I-131 therapy. The nuclear medicine physician recorded his preimaging diagnostic impression and therapeutic plan for each patient. After the [ 99mTc ] pertechnetate image, the patient was reassessed to determine whether the image induced any change in the diagnosis or therapeutic plan. Seventy-nine of 80 patients with diffuse goiter to palpation, had scintigrams demonstrating no discrete focal defects and were diagnosed as Graves' disease; thus the scintigram did not contribute useful information. In 17 of 20 patients with uninodular or multinodular goiters, the image was necessary to clarify the final diagnosis and therapeutic plan. Thus, selective use of thyroid scintigraphy should decrease the number of scintigrams performed before I-131 therapy for hyperthyroidism, without compromising diagnostic accuracy or therapeutic success.     

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 (131I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule. The risk of development of hypothyroidism is low if extranodular uptake of 131I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.     

Graves' ophthalmopathy and 131I therapy.

Graves' ophthalmopathy is an autoimmune process initiated and maintained by antigen(s) shared by the thyroid and the orbit. A matter of argument concerns the choice of the method of treatment for Graves' hyperthyroidism when clinically evident ophthalmopathy is present. Restoration of euthyroidism appears to be beneficial for ophthalmopathy. On the other hand the continuing disease activity associated with the recurrence of hyperthyroidism appears to adversely affect the course of ophthalmopathy. For these reasons it is our opinion that in patients with Graves' hyperthyroidism and ophthalmopathy the permanent control of thyroid hyperfunction by ablation of thyroid tissue should be obtained by radioiodine therapy or thyroidectomy. The rationale for an ablative strategy is the following: i) permanent control of hyperthyroidism avoids exacerbations of eye disease associated with recurrence of hyperthyroidism; ii) hypothyroidism, which follows thyroid tissue ablation, should be regarded as a therapeutic end point rather than as an undesirable result; iii) ablation of thyroid tissue may result in the removal of both the thyroid-orbit cross-reacting antigen(s) and the major source of thyroid-autoreactive lymphocytes. The relationship between radioiodine therapy and the course of GO is a matter of controversy, and some authors have suggested that radioiodine administration may be associated with a worsening of preexisting ophthalmopathy. This was not observed when radioiodine treatment was associated with a 3-month oral course of prednisone. The development or progression of GO after radioiodine therapy might be due to the release of thyroid antigens following radiation injury and to subsequent exacerbations of autoimmune reactions directed towards antigens shared by the thyroid and the orbit. The view that radioiodine therapy may be associated with a progression of ophthalmopathy is not shared by some authors who claim that the apparent link between progression of ophthalmopathy and radioiodine therapy might simply be coincidental, reflecting the natural history of the disease. The radioiodine-associated exacerbation of eye disease might be used as an argument against the use of radioiodine therapy in patients with ophthalmopathy. We do not share this view, since the outward effects of radioiodine on eye disease can easily be prevented by concomitant administration of glucocorticoids. Glucocorticoid treatment should be limited, in our opinion, to patients with clinically evident eye disease and to those without ophthalmopathy but with other known risk factors, such as smoking.     

Determination of the autonomously functioning volume of the thyroid

The aim of this work was to determine the autonomously functioning volume in euthyroid and hyperthyroid goitres for prognostic and therapeutic purposes. To this end, various groups of patients were selected: individuals without evidence of thyroid disease, euthyroid patients with diffuse goitre of normal structure and function, euthyroid patients with evidence of autonomy and patients with hyperthyroidism due to autonomy. In all of them the thyroid uptake of technetium-99m was determined under exogenous suppression (TcU_s) in the euthyroid state and under endogenous suppression (TcU) in the hyperthyroid state. It was demonstrated that:

1. In patients with unifocal autonomy the TcU_s and TcU correlated linearly with the autonomous volume delineated and measured by sonography.
2. A nearly identical result was obtained if the mean autonomous volume in individuals without thyroid disease of 2.2 ± 1.1 ml calculated by TcU_s/TcU x total thyroid volume was used as a basis.
3. The critical autonomous volume, i.e. the volume at which hyperthyroidism will occur, was found to be 16 ml at a cumulated sensitivity and specificity of >0.9.

The method can be used to select patients for definitive treatment before hyperthyroidism occurs and to measure the autonomously functioning volume independent of its distribution within the thyroid for treatment with radioiodine. The method is easy to perform and is also an example of how a relative parameter of a function can be converted into an absolute parameter of a functioning volume.     

Incidence of radiation-induced Graves’ disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD.     

The role of thyroid scanning in hyperthyroidism

Radionuclide thyroid imaging was performed in 872 consecutive patients with hyperthyroidism. Of these, 84% were found to have diffuse toxic hyperplasia (Graves' disease), while 12% had autonomously functioning nodules (Plummer's disease), 3% had Graves' disease developing in a multinodular gland, and in the remaining 1%, either a clear diagnosis could not be established or the hyperthyroidism was due to thyroiditis or the Jod-Basedow phenomenon. It was found that a thyroid scan seldom provides additional diagnostic information in patients with Graves' disease when a diffuse goitre is present. However, if patients are to be treated with radioiodine (131I), thyroid imaging with tracer quantitation can replace a 24-h 131I uptake measurement, this having the advantages that the patients are required to attend only once, and that the gland size can be measured. In addition, visual confirmation of tracer uptake by the thyroid is obtained and patients with thyroiditis will not receive inappropriate therapy. When single or multiple thyroid nodules are palpated, a thyroid scan is crucial in establishing an accurate diagnosis, as it is not otherwise possible to differentiate between Plummer's disease and Graves' disease developing in a multinodular gland. Indeed, in 20 of our 63 patients (32%) with single autonomously functioning nodules, the initial clinical assessment had been incorrect.     

Hypothyroidism presenting as a hot pertechnetate nodule

The authors report an uncommon finding of hot nodule on Tc-99m sodium pertechnetate thyroid scan in three patients with hypothyroidism. Data indicate that hypothyroidism is secondary to Hashimoto's disease (HD). There was a concordant aspect on I-131 scan in two; a nodular discrepancy (cold nodule with I-131) was associated with the highest microsomal antibodies titer. The findings of thyroid scan and ultrasonographic findings indicate that hot nodules may be observed either on initial or advanced stages of HD. Color flow Doppler sonography, showed an absence of internal increase of vascularization. These data suggest that the observed hot nodules correspond to localized hyperplasia of the less diseased portions secondary to chronic stimulation by TSH.