Types Of Hyperthyroidism Research Articles

Differentiation between the two types of amiodarone-associated thyrotoxicosis using duplex and amplitude doppler sonography

To evaluate the usefulness of Doppler parameters in the differentiation between the two types of amiodarone-associated thyrotoxicosis (AAT). One hundred thirty-seven individuals were selected at our institution. They were divided into four groups: 84 normal subjects (N), 30 euthyroids taking amiodarone (A), 14 AAT type 1 patients (AAT1), and nine AAT type 2 patients (AAT2). Each AAT type was classified according to (131)I uptake and clinical outcome. Blindly, the resistance and pulsatility indexes (RI, PI), systolic peak velocity, and color pixel density (CPD) were calculated. AAT1 had greater CPD than AAT2 (P = 0.02). The latter group had similar vascularization to the N and A groups (P = 0.45). The area under the receiver operating characteristic (ROC) curve showed that systolic peak velocity in the inferior thyroid arteries and CPD were the best parameters in the differentiation between AAT type 1 and AAT type 2 (Az = 0.83 and 0.84, respectively). Impedance indexes were useless. Our results demonstrate that objective tests such as systolic peak velocities in the thyroid arteries and CPD are reliable parameters for differentiating between the two types of AAT.

Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves’ disease

Differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis is important for selection of proper therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We investigated the possibility that assessment of thyroid blood flow would allow differentiation between the two entities. One hundred and fourteen untreated patients with thyrotoxicosis (56 Graves' disease, 28 painless thyroiditis, 30 subacute thyroiditis) and 25 normal controls were examined. Serum levels of freeT4 (FT4), freeT3 (FT3) and TSH were measured by chemiluminescent immunoassay, and anti-TSH receptor antibodies (TSH-binding inhibitory immunoglobulin, TBII) were measured by enzyme-linked immunosorbent assay. Thyroid volume and blood flow (TBF) were measured quantitatively by ultrasonography. TBF was significantly higher in Graves' disease (mean +/- 1SD: 14.9 +/- 6.4%, P < 0.0001) than in painless thyroiditis (0.8 +/- 0.5%), subacute thyroiditis (0.9 +/- 0.7%) and in normal controls (0.8 +/- 0.5%). All patients with Graves' disease had TBF values of more than 4% and all patients with painless thyroiditis and subacute thyroiditis had TBF values less than 4%. TBF values significantly correlated with values of radioactive iodine uptake (RAIU) either at 3 h (r = 0.492, P < 0.01) or 24 h (r = 0.762, P < 0.001) within the Graves' disease and painless thyroiditis groups. There was no relationship between TBF values and thyroid volumes or values of TBII in the Graves' disease group. All patients with Graves' disease had positive TBII of 15% or more. Three of 28 patients with painless thyroiditis and one of 30 patients with subacute thyroiditis had positive TBII. TBF was quantitatively measured by power Doppler ultrasonography and was more effective than TBII for differentiation between destruction-induced thyrotoxicosis (painless or subacute thyroiditis) and Graves' thyrotoxicosis. TBF values of less than 4% in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.

Sodium Iodide Symporter Is Expressed at the Preneoplastic Stages of Liver Carcinogenesis and in Human Cholangiocarcinoma

The ability of thyroid cells to take up iodide, which enables (131)I radiotherapy for thyroid cancer, is due to the expression of the sodium iodide symporter at their plasma membrane. Expression of this symporter has been found in some nonthyroid cancers. However, it is mostly accumulated in the cytoplasm, and its functionality has not been demonstrated. We have investigated sodium iodide symporter expression and functionality in human liver cancer, and in a diethylnitrosamine induced Wistar rat model of primary liver cancer at different stages of carcinogenesis. Sodium iodide symporter mRNA and protein were studied in tissues from patients with hepatocellular- or cholangio-carcinomas using reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemistry. We studied the dynamics of hepatic iodine uptake in the animal model using nuclear imaging. Sodium iodide symporter expression showed up in all 20 cholangiocarcinomas, but in only 2 of the 26 hepatocellular carcinomas, investigated. It was also found in normal bile duct cells and in the ductular reaction present in cirrhotic tissues. It was located at the plasma membrane in 10 of 20 cholangiocarcinoma. In rat liver cancer, a functional sodium iodide symporter expression was triggered as from the early preneoplastic steps, and was amplified during clonal tumor cell expansion, allowing complete tumor suppression after (131)I radiotherapy. A significant proportion of human cholangiocarcinomas expresses membrane sodium iodide symporter, which may permit radioiodine therapy. Our data also suggest that (131)I acts on a crucial target for liver cancer development.

2163: Value of objective color Doppler ultrasound parameters in the differentiation between amiodarone-induced thyrotoxicosis Type I and II: ROC analysis

Objectives: Color-Doppler ultrasound (CDUS) has been used for the differentiation between the two types of amiodarone-induced thyrotoxicosis(AIT). However, until now all criteria used were based on the subjective analysis of the vascularization, which makes it possibly imprecise. The aim of this study was to test the objective Doppler parameters through ROC analysis.

Amiodarone-Induced Thyrotoxicosis Due to Destructive Thyroiditis

Amiodarone-induced thyrotoxicosis (AIT) type 1 occurs in subjects with an underlying thyroid disease, whereas type 2 AIT is a form of destructive thyroiditis. Our hypothesis was that the common practice of thyroid testing before prescription of amiodarone would reduce the incidence of pure type 1 AIT, though a stringent classification may be difficult (mixed type AIT). Thyroid testing before and after treatment of AIT (n = 12) and the response to combined antithyroid and glucocorticoid treatment (n = 11) were recorded in a consecutive series of patients seen at a university hospital. Some criteria for type 1 AIT were fulfilled in 3 patients, but the diagnosis of a mixed form AIT was more likely in 2 of these. Type 2 AIT was diagnosed in the other 9 patients, while 6 patients had diffuse hypoechoic goitre. The median time to euthyroidism (defined as normal fT3 concentration) under thionamide and prednisolone (starting dose 20 to 75 mg/d) was 2 months (interquartile range 1 to 2.7 months). Thionamide treatment was stopped after a median duration of 5.7 months (interquartile range 4.2 to 8.7 months) and glucocorticoids were completely withdrawn after 6.7 months (5.5 to 8.7 months). Nowadays, isolated type 1 AIT is rarely found and destructive thyroiditis (as type 2 AIT or mixed form) is the predominant cause of AIT. To accelerate recovery, we prescribed thionamide and glucocorticoids simultaneously as first-line therapy once contraindications for the use of steroids had been ruled out.

Usefulness of the 2nd Generation Assay for Anti-TSH Receptor Antibodies to Differentiate Relapse of Graves' Thyrotoxicosis from Development of Painless Thyroiditis after Antithyroid Drug Treatment for Graves' Disease

After antithyroid drug (ATD) treatment for Graves' disease, either a relapse of Graves' thyrotoxicosis or painless thyroiditis can develop. It is important to differentiate these two types of thyrotoxicosis because of the difference in required therapy. However, differentiation of thyrotoxicosis is usually difficult without radioactive iodine uptake (RAIU) which is not available in general practice. We investigated the clinical usefulness of the 2nd generation assay for anti-TSH receptor antibodies (TRAb) to differentiate these two types of thyrotoxicosis after ATD treatment for Graves' disease. We recruited 26 patients who developed thyrotoxicosis after ATD treatment for Graves' disease. These patients once became negative for TRAb and seemed to be in remission after ATD treatment. Upon development of thyrotoxicosis after ATD treatment, TSH, free T4, free T3 and TRAb were measured. TRAb were measured by the 2nd generation assay using recombinant human TSH receptors instead of porcine TSH receptors. Fourteen patients relapsed into Graves' thyrotoxicosis and 12 patients developed painless thyroiditis. Twelve (85.7%) of 14 patients with relapse of Graves' thyrotoxicosis were positive for TRAb. Eleven (91.7%) of 12 patients with development of painless thyroiditis after ATD treatment for Graves' disease were negative for TRAb. Levels of TRAb were significantly different between patients with relapse of Graves' thyrotoxicosis (4.86 +/- 6.45 IU/L) and those with painless thyroiditis (0.62 +/- 0.61 IU/L) (P<0.001). The 2nd generation assay for TRAb was useful to differentiate relapse of Graves' thyrotoxicosis from development of painless thyroiditis in patients who seemed to be in remission after ATD treatment for Graves' disease.

Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis.

Differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis is important for selection of therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We searched for simple and practical parameters that might allow differentiation between the two entities. One hundred and eleven untreated patients with thyrotoxicosis (69 Graves' disease, 21 painless thyroiditis, 21 subacute thyroiditis) and 45 normal controls were examined. Serum levels of free T4 (FT4) and free T3 (FT3) were measured by radioimmunoassay, and anti-TSH receptor antibodies (TBII) were measured by radioreceptor assay. Peripheral leucocyte counts and the percentages of eosinophils and monocytes were measured using an automated leucocyte differential system. Peripheral eosinophils were significantly higher in Graves' disease (3.54 +/- 4.18%, P < 0.05) and lower in subacute thyroiditis (1.08 +/- 1.03%, P < 0.001) than in normal controls (2.26 +/- 1.33%). Peripheral monocytes were significantly higher in painless thyroiditis (6.87 +/- 2.85%, P < 0.01) than that in normal controls (4.63 +/- 2.14%). In comparison between groups, FT3 was higher with Graves' disease (20.55 +/- 10.29 pmol/l) than both painless thyroiditis (11.59 +/- 8.22 pmol/l, P < 0.001) and subacute thyroiditis (15.27 +/- 8.63 pmol/l, P < 0.05). The eosinophil to monocyte (Eo/Mo) ratio, FT3/FT4 ratio and Eo/Mo ratio multiplied by FT3 (pmol/ml) (Eo/Mo.FT3) were calculated and compared in these three disease groups. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were significantly higher in patients with Graves' thyrotoxicosis (0.782 +/- 0.759, 0.399 +/- 0.089, 16.7 +/- 23.5 pmol/l, respectively) than in those with painless thyroiditis (0.259 +/- 0.157, 0.304 +/- 0.072, 2.43 +/- 1.49 pmol/l, respectively) and subacute thyroiditis (0.234 +/- 0.241, 0.335 +/- 0.057, 2.98 +/- 3.51 pmol/l, respectively). Twenty-two of 24 (91.7%) thyrotoxic patients with Eo/Mo < 0.2 had destruction-induced thyrotoxicosis (painless or subacute thyroiditis). Twenty-two of 28 (78.6%) thyrotoxic patients with FT3/FT4 < 0.3 had destruction-induced thyrotoxicosis. Thirty-six of 42 (85.7%) thyrotoxic patients with Eo/Mo.FT3 < 4.5 had destruction-induced thyrotoxicosis. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were found to be similarly useful for differentiation between the two types of thyrotoxicosis. All thyrotoxic patients with TBII > or = 20% had Graves' disease and 76.4% of patients with TBII < 20% had destruction-induced thyrotoxicosis. The Eo/Mo ratio, FT3/FT4 ratio, and Eo/Mo.FT3 are simple, practical parameters and were as effective as TBII for differentiation of destruction-induced thyrotoxicosis (painless or subacute thyroiditis) from Graves' thyrotoxicosis. Eo/Mo < 0.2 and/or Eo/Mo.FT3 < 4.5 in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis, and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.

Epidemiological survey on the relationship between different iodine intakes and the prevalence of hyperthyroidism.

To investigate the effect of different levels of iodine intake on the prevalence of hyperthyroidism and the impact of universal salt iodization on the incidence of hyperthyroidism. A comparative cross-sectional and longitudinal survey was conducted in three areas with borderline iodine deficiency, mild iodine excess (previously mild iodine deficiency) and severe iodine excess. Universal salt iodization had been introduced 3 years previously except in the area with borderline iodine deficiency. In total 16 287 inhabitants from three areas answered a questionnaire concerning the history of thyroid disease. Among them 3761 unselected subjects received further investigations including thyroid function, thyroid autoantibodies, thyroid ultrasonography and urinary iodine excretion. Among areas with median urinary iodine excretion of 103 microg/l, 375 microg/l and 615 microg/l (P<0.05), the prevalence of hyperthyroidism did not differ significantly (1.6%, 2% and 1.2%). The prevalence of subclinical hyperthyroidism was higher in areas with borderline iodine deficiency and mild iodine excess than in the area with severe excess iodine intake (3.7%, 3.9% and 1.1%, P<0.001). The prevalence of Graves' disease and its proportion in hyperthyroidism did not differ among areas. The incidence of hyperthyroidism did not significantly increase after the introduction of universal salt iodization. Different iodine intakes under a certain range do not affect the prevalence and type of hyperthyroidism. Subclinical hyperthyroidism is more prevalent in the iodine deficient area than in the severe iodine excessive area. In the area with mild iodine deficiency, the introduction of universal salt iodization may not be accompanied by an increased incidence of hyperthyroidism.

Grey scale thyroid ultrasonography in the evaluation of patients with Graves' disease.

Graves’ disease is a genetically induced autoimmune disorder characterized by hyperthyroidism due to circulating thyroid stimulating hormone (TSH) receptor autoantibodies (TRAb) with thyroid stimulating activity (1). Graves’ disease is the most common cause of hyperthyroidism, which has an estimated prevalence in iodine sufficient areas of 20/1000 females and 2.3/ 1000 males (2). It is most common in females between the ages of 20 and 50 years, but it may occur at any age. The laboratory diagnosis of Graves’ disease is based on the finding of high serum thyroid hormone and undetectable serum TSH concentrations associated with circulating thyroglobulin and thyroperoxidase antibodies. TRAb is detectable in almost 90% of patients, but usually it is not needed for the diagnosis. Radioisotope scan of the thyroid shows a diffuse and homogeneous radionuclide uptake. Treatment strategies for Graves’ hyperthyroidism include medical therapy with antithyroid drugs (ATD) or thyroid ablation with 131 I or surgery. ATD, mainly thionamides, inhibit thyroid hormone synthesis by blocking iodine organification catalysed by thyroid peroxidase. Treatment of Graves’ disease with thionamides is mainly performed in Europe and in Japan, while in the USA and Canada radioiodine is commonly preferred as the first choice treatment (3). Many studies have been undertaken to find parameters which help predict the clinical outcome of Graves’ hyperthyroidism after ATD withdrawal. Among them, TRAb measurement at the end of an ATD course was found to be the most predictive (4, 5). After its introduction into clinical practice in the late sixties, thyroid ultrasonography (US) proved to be very effective in the diagnostic approach to thyroid diseases, the anatomical location of the gland being advantageous for this technique. The most widely used application of thyroid US is identification and characterization of thyroid nodules (6). Rapid improvements in the development of US equipment have made available real-time high frequency transducers (7.5‐ 10 MHz) with high resolution, which allow a more precise definition of the echostructure of the thyroid tissue. In addition, recently developed color Doppler technology allows determination of the blood flow through the gland, offering the possibility of recording objective measurements, such as the peak systolic velocity of the blood flow at the level of thyroid arterial vessels (i.e. inferior thyroid artery). Using these techniques, thyroid blood flow has been shown to be correlated with the thyroid status in patients with Graves’ disease, being markedly increased in 17/18 patients with untreated active hyperthyroidism and less clearly increased in treated patients. In patients with Hashimoto’s thyroiditis, the thyroid blood flow was not correlated to thyroid status or treatment and was never markedly increased (7). Color Doppler sonography was also shown to be useful in distinguishing cases of destructive thyrotoxicosis by amiodarone (i.e. amiodarone thyrotoxicosis type 2), characterized by a low thyroid blood flow, from cases in which thyroid hyperfunction also occurs (i.e. amiodarone thyrotoxicosis type 1), characterized by an increased thyroid

Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis.

Recent increases in the sensitivity of methods used to measure TSH, especially third generation assays, have enabled separation of partial from complete pituitary suppression in patients with thyrotoxicosis. We have investigated the use of a sensitive chemiluminescent enzymeimmunoassay in the differential diagnosis of thyrotoxicosis. Serum TSH concentrations were determined by chemiluminescent enzymeimmunoassay in patients with various types of overt and subclinical thyrotoxicosis. The assay was highly sensitive with an analytical sensitivity of 0.0016 mU/l. Among 45 hyperthyroid patients with untreated Graves' disease, 37 (82.2%) showed undetectably low levels (< 0.002 mU/l). Serum TSH in the remaining 8 patients (17.8%) was 0.003-0.005 mU/l. In contrast, TSH was undetectably low in only 5 (20.0%) of 20 patients with painless thyroiditis and in 2 (12.5%) of 16 patients with subacute thyroiditis. Eleven (55.0%) with painless thyroiditis and 12 (75.0%) with subacute thyroiditis had TSH values greater than 0.005 mU/l (0.006-0.032 and 0.006-0.228 mU/l, respectively; normal range 0.5-5.0 mU/l). Serum TSH levels were subnormal in 10 of 12 patients with euthyroid ophthalmic Graves' disease, including 4 with undetectably low levels. Among 11 patients with an autonomously functioning thyroid nodule 6, including 1 with normal free T4 and free T3 and 2 with normal free T3, showed TSH values less than 0.002 mU/l. No significant correlation was observed between serum free T4 or free T3 and TSH concentrations in thyrotoxic patients. Together with the incomplete suppression of TSH observed in those with destructive thyroiditis, this suggests that the grade of TSH suppression was influenced by the duration of illness at the time of blood sampling. The third-generation TSH assay is useful for the differential diagnosis of various types of thyrotoxicosis, especially between Graves' disease and destructive thyroiditis.

Adenoma tireoideano tóxico: aspectos clínicos e conduta

Adenoma tireoideano tóxico é uma das principais etiologias do hipertireoidismo, ao lado da Doença de Graves e do Bócio Multinodular Tóxico. Apresenta incidência variável nos diferentes países (2 a 33%), ocorrendo principalmente em áreas carentes em iodo. É mais freqüente em mulheres e no grupo etário mais idoso. Estudos recentes apontam para mutação do gene que expressa o receptor do TSH ou da proteína G como causas do aparecimento do adenoma. As características clínicas de um nódulo autônomo tóxico são similares às de outras formas de tireotoxicose, porém, pela maior incidência em um grupo etário mais idoso, há menor exuberância dos sintomas com predomínio das manifestações cardiovasculares. Os pacientes comumente se apresentam pelo nódulo tireoideano, com níveis elevados dos hormônios tireoideanos e supressos de TSH. O diagnóstico é confirmado pela presença de nódulo quente ao mapeamento com 131I,123I ou 99mTc. Os tratamentos clássicos preconizados, para corrigir a tireotoxicose, são a terapia cirúrgica ou com radioiodo e, mais recentemente, a injeção percutânea com etanol dirigida por ultra-som, uma vez que a resolução espontânea do processo é muito rara.

The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

Incomplete thyrotroph suppression determined by third generation thyrotropin assay in subacute thyroiditis compared to silent thyroiditis or hyperthyroid Graves' disease.

Serum TSH concentrations were determined by both second and third generation assays in three types of thyrotoxicosis associated with subacute thyroiditis, silent thyroiditis, and hyperthyroid Graves' disease at the time of each patient's initial visit to the clinic. Serum TSH concentrations as measured by the second generation assay with an analytical sensitivity of 0.04 mU/L were below the detection limit in every patient. In contrast, serum TSH concentrations as measured by the third generation assay with an analytical sensitivity of 0.009 mU/L were below the detection limit in 18 of 21 (86%) patients with Graves' disease, 18 of 20 (90%) with silent thyroiditis, but only 4 of 18 (22%) with subacute thyroiditis. Changes in serum TSH concentrations were studied in healthy volunteers given daily 75 micrograms of T3; their serum TSH concentrations on the second generation assay fell below the detection limit within 3 days in every subject. However, the TSH concentration measured by the third generation assay remained above the detection limit in 6 of 8 normal subjects even on the 14th day of therapy. The reason for incomplete TSH suppression in most subacute thyroiditis patients may be that these patients had notable neck pain, and their initial visit to the clinic may have occurred earlier after the onset of disease than with patients who have had silent thyroiditis or Graves' disease. Thus, the serum TSH concentration had not decreased sufficiently below the detection limit at the time blood was drawn. The data suggest also that the highly sensitive TSH assay, if the level is above the detection limit, can be used to suppose that the short duration of the initiation of thyrotoxicosis indicates a case of subacute thyroiditis.

Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves' disease.

Patients with T3-predominant Graves' disease have an increased serum T3 level despite a normal or even lower level of serum T4 caused by antithyroid drug treatment. This study investigated the morphological characteristics of the thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but thyroid weight was significantly greater in T3-predominant Graves' disease than in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height of thyroid follicular epithelial cells were significantly greater in T3-predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1 microns), but the epithelial height did not correlate significantly with the serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of the total thyroid tissue in T3-predominant Graves' disease, while they occupied only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/- 1.0% for controls). These findings suggest that the thyroid gland is more active in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal iodine than in the ordinary type of Graves' disease.

Thyroid Radioiodine Uptake

Although in vitro measurements of serum thyroid hormones and particularly the sensitive TSH assay have in recent years taken over as first-line tests, measurement of the thyroid radioiodine uptake (RAI-U) still has a a place in the diagnosis of thyroid dysfunction in certain specific circumstances. The widespread availability of short-lived radionuclides (iodine-123 and Tc-99m) allows in vivo thyroid uptake and imaging to be carried out with much lower radiation exposure to the patient than in the past, when I-131 was the only radionuclide available. RAI-U testing is probably most useful in the differentiation of various types of thyrotoxicosis in those patients in whom clinical and laboratory findings do not clearly point to the etiology of the condition. Thus, the RAI-U will usually distinguish between true hyper-thyroidism and thyrotoxicosis caused by either a destructive, self-limited form of thyroiditis or ingestion of excess thyroid hormone (factitious thyrotoxicosis). Other clinical indications for the RAI-U include calculating the proper therapeutic dose of I-131 for hyperthyroidism, determining the presence of autonomous function of the thyroid in patients receiving thyroid hormone, and investigating the nature of intra-thyroidal defects in iodine metabolism. Excessive intake of iodine, most commonly in the form of medication or as radiographie contrast dyes, is the major cause of falsely low RAI-U results. This is one reason why the test is of no value in the diagnosis of atrophie thyroid failure. Another limitation of the RAI-U is the fact that elderly patients with hyperthyroidism, particularly with nodular goiter, commonly have RAI-U values within the normal range. Nevertheless, when the limitations are kept in mind, the RAI-U is a valuable adjunct to thyroid testing in selected cases.

Usefulness of thyroglobulin antibody detected by ultrasensitive enzyme immunoassay: a good parameter for immune surveillance in healthy subjects and for prediction of post-partum thyroid dysfunction.

Using newly developed ultrasensitive enzyme immunoassay (EIA) for thyroglobulin antibody (TgAb), we have evaluated physiological and pathological implications of the antibody in healthy subjects as well as in autoimmune thyroid diseases. This EIA was based on the immune complex transfer method, and was 10(4)-fold more sensitive compared with the conventional haemagglutination assay (HA); the detection limit was 0.1 micrograms IgG/I, and the specificity of the assay was confirmed from the unequivocal decrease in the fluorescence intensity by the preincubation of test serum with Tg and/or inactive beta-D-galactosidase which blocks antibodies to the enzyme. TgAb was detectable in 159 (91%) of 175 healthy subjects aged 3rd to 7th decade (96 men and 79 women), and did not exhibit age or sex-associated change. In nine healthy women, the TgAb level significantly decreased as pregnancy progressed but increased transiently after delivery. TgAb was detectable in 52 (98%) of 53 patients with Graves' disease and all (100%) of 107 patients with chronic thyroiditis. Abnormal high TgAb values (> 40 micrograms/I), determined from the 95th percentile in healthy subjects, were shown in 40 (75%) with the former disease and 94 (88%) with the latter disease. Moreover, in 14 goitrous patients with biopsy-proved chronic thyroiditis with negative HA results, 12 (86%) showed abnormal high TgAb levels. In 69 patients with post-partum thyrotoxicosis in Graves' disease, 15 (79%) of 19 patients with the TgAb level of more than 2 x 10(3) micrograms/I in early pregnancy showed destructive thyrotoxicosis and 46 (92%) of 50 with less than this level showed stimulative thyrotoxicosis. This TgAb test could discriminate the two types of thyrotoxicosis more clearly than could the conventional TGHA test. In chronic thyroiditis, the mean TgAb value in early pregnancy was significantly higher in patients with postpartum hypothyroidism than in those without thyroid dysfunction. Hypothyroidism developed in 80% of the patients with a TgAb value of more than 10(3) micrograms/I. The ultrasensitive TgAb EIA was useful for detecting the physiological changes in autoantibody formation in healthy subjects and the TgAb value was useful for predicting post-partum thyroid dysfunction in autoimmune thyroid diseases. This EIA is useful for the evaluation of the immune surveillance in patients with autoimmune thyroid diseases as well as in healthy subjects.

High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East‐Jutland Denmark and Iceland

Little is known about the optimum level of iodine intake for iodine supplementation programmes, or about the effects of the high levels of iodine intake that are found in some countries. We compared the incidence of different types of hyperthyroidism in East-Jutland Denmark with a low average iodine intake but no endemic goitre, and the incidence in Iceland with a relatively high iodine intake. Hyperthyroidism was more common in East-Jutland than in Iceland, due to a much higher incidence of multinodular toxic goitre and also of single toxic adenoma. Most of the patients with these diseases were over 50 years of age. By contrast, the incidence of Graves' disease was significantly higher in Iceland than in East-Jutland. This difference was most marked in the younger age groups, in which hyperthyroidism was more than twice as common in Iceland as in East-Jutland. These results demonstrate that even mild iodine deficiency has a significant effect on population health, since it leads to a high incidence of autonomous thyroid nodules with hyperthyroidism in the elderly population. However, population iodine intake probably should not exceed a level much higher than that necessary to avoid iodine deficiency, otherwise Graves' disease may be induced in the young population.

Is idiopathic atrial fibrillation caused by occult thyrotoxicosis? A study of one hundred consecutive patients with atrial fibrillation

In this study we evaluated the possible relationship between idiopathic atrial fibrillation and occult thyrotoxicosis, diagnosed by lack of response of thyroid stimulating hormone to administration of thyrotropin releasing hormone. Three groups were compared: 25 patients with idiopathic atrial fibrillation; 52 with cardiovascular atrial fibrillation; and 27 with sinus rhythm. Patients were excluded with any clinical evidence of thyrotoxicosis or with elevated serum FT 4 level, as well as those with diseases or on medications known to be associated with a diminished response to administration of the releasing hormone. A flat test (lack of response) was found in only 4% of the patients. There was no significant difference among the 3 groups. Based on these data we believe that there is no relationship between idiopathic atrial fibrillation or any other type of atrial fibrillation and occult thyrotoxicosis.

Prolapse of the mitral valve in hyperthyroid patients in Saudi Arabia

Eighty-two patients (60 females and 22 males) who were under treatment for hyperthyroidism at the King Saud University affiliated hospitals in Riyadh, Saudi Arabia, were evaluated by M-mode and cross-sectional echocardiography for the presence of mitral valve prolapse. Sixty-seven patients (51 females and 16 males) had diffuse toxic goitre while 15 of them (9 females and 6 males) had nodular toxic goitre. The overall frequency of prolapse was 37.8% (31 of 82) and the frequency was similar for both sexes, being 38.3% in females and 36.3% in males. Prolapse was associated with both diffuse toxic goitre (overall frequency 35.8%) and nodular toxic goitre (overall frequency 46.6%); and the highest frequency was in females with nodular toxic goitre (55.5%). Out of the total of 31 patients with prolapse, early systolic and holosystolic prolapse were each present in 12 patients, while mid-to-late systolic prolapse was found in 7 patients. Cross-sectional echocardiography demonstrated prolapse in 16 cases, the M-mode was positive in 5 cases while the two methods confirmed it in 10 patients. The prevalence of prolapse of the mitral valve in otherwise healthy Saudi subjects has previously been found to be 12–15%. This study has confirmed a high frequency of prolapse in hyperthyroid patients and has demonstrated that sex, ethnic or racial origin and type of hyperthyroidism are not determinants of this association.

The different types of hyperthyroidism in Europe. Results of a prospective survey of 924 patients.

In a prospective multicentric study, 924 untreated hyperthyroid patients were investigated, coming consecutively within one year into 17 thyroid centers of 6 European countries. With the aid of clinical information, evaluation of thyroid scan and centrally assayed thyroid hormones, thyroid antibodies, TSH-binding inhibiting immunoglobulins (TBII), and urinary iodine, different types of hyperthyroidism could be shown. Two types of hyperthyroidism could be defined directly: autonomous adenoma in cases of hot nodules in thyroid scan and Graves' disease, defined as hyperthyroidism with eye symptoms, and/or measurable TBII levels. The remainder, called "non-classifiable", included TBII negative Graves' patients, comprising of Hashitoxicosis, toxic nodular goiter, and other multifocal autonomies. 9.2% of the patients had an autonomous adenoma, 59.6% Graves' disease, and 31.2% unclassified hyperthyroidism. The main and significant difference between these types were mean age, goiter size, nodularity, and severity of the disease, being especially expressed in Graves' disease. Graves' patients had significantly increased T3/T4 ratios. Using as additional criteria diffuse regular uptake and/or increased T3/T4 ratios for immunogenic types of hyperthyroidism at least half of the 31.2% unclassified hyperthyroidism are probably Graves' disease. Forming two groups of iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. Autonomous adenoma was more frequent in IDA (10.1%) than in ISA (3.2%). Differences in iodine supply are reflected in the three types of hyperthyroidism by a significant higher prevalence of goiter, thyroid nodularity, lower thyroid hormone concentrations, and a higher rate of T3 toxicosis in IDA.(ABSTRACT TRUNCATED AT 250 WORDS)