Thyrotoxic crisis in Graves' disease: Indication for immediate surgery

Summary Thyrotoxic crisis (thyroid storm) is a rare complication of hyperthyroidism. It can be observed not only in thyroid autonomy with latent hyperfunction after exposure to iodine, but also in Graves' disease with overt hyperfunction. Adequate management of thyrotoxic crisis is still controversial. We report about four patients (four women, mean age 75 years) with Graves' disease who developed thyrotoxic crisis during therapy with antithyroid drugs so that surgical intervention became necessary. The patients had been admitted to the hospital for nonspecific symptoms such as headache, cachexy, and psychosis. Thyroid hormone levels had reached twice the normal range prior to surgery. All patients showed severe neurological deficits leading to coma. In three cases euthyroidism was achieved within two days after surgery. The neurological symptoms disappeared after an average of four days. The postoperative course did not show severe complications and all patients recovered completely.Especially in the elderly a monosymptomatic or nonspecific course of thyroid storm with neurological symptoms may represent a severe and life-threatening situation. In these cases surgery can become necessary even if euthyroidism has not been achieved preoperatively.Abbreviations dl deciliter - FT3 free triiodthyronine - FT4 free thyroxine - Hg mercury - l liter - MAK microsomal antibodies - mg milligram - ml milliliter - mU milliunit - ng nanogram - T3 triiodthyronine - T4 thyroxine - TAK thyroglobulin antibodies - TBG thyroxine-binding globulin - TRAK TSH-receptor antibodies - TRH thyrotropin-releasing hormone - TSH thyroid-stimulating hormone - TT3 total triiodthyronine - TT4 total thyroxine - g microgram     

联合应用抗甲状腺药物和甲状腺激素治疗Graves病的效果评价

本文研究抗甲状腺药物（ＡＴＤ）单独或与甲状腺激素联合应用，对Ｇｒａｖｅｓ病（ＧＤ）病情演变和转归的作用。联合用药组血清甲状腺刺激抗体（ＴＳＡｂ）下降的幅度明显大于单独应用ＡＴＤ组，其血清ＴＳＨ水平、药物性甲减的发病率以及停药后甲亢的复发率均显著低于单独用药组。提示ＡＴＤ与甲状腺制剂联合应用对ＧＤ具有更好的治疗效果。     

Prognostic value of thyroid stimulating antibodies and TSH-binding inhibiting immunoglobulins in the follow-up of Graves' disease

Summary The prognostic value of the determinations of autoantibodies in Graves' disease is still questionable. So far, the role of different assay procedures used has not been intensively investigated. We simultaneously applied two different techniques, a radioreceptor assay and a T3 releasing in vitro assay, in the follow-up of patients with Graves' disease to directly compare the course of the antibody activities determined by these assays and to find out a prognostic significance of the composition of the antibody spectrum present. The initial activities of thyroid stimulating antibodies (TSAb) and TSH-binding inhibiting immunoglobulins (TBII) were not significantly correlated in patients before treatment. During a 12-month antithyroid medication antibody titres showed a concordant course in the majority of patients. In 6 of 25 patients, however, a discordant behaviour was clearly documented including dose-response curves. At the end of treatment, the patients could be divided into three groups: group I included 5 patients positive for both TSAb and TBII, group II 6 patients positive for TBII and negative for TSAb and group III 14 patients negative for both of them. During the following survey of 18 months all patients of group I, 2 patients of group II and 6 patients of group III experienced a relapse of hyperthyroidism. In conclusion, TSAb and TBII activities dissociate in some patients during antithyroid drug therapy. For the individual patient, the disappearance of both TSAb and TBII was no certain indicator for a longstanding remission of Graves' hyperthyroidism. The persistence of TSAb seems to be more reliably associated with persisting or rapidly relapsing disease than the persistence of TBII.Abbreviations cAMP Cyclic Adenosine Monophosphate - GD Graves' disease - T3 Triiodothyronine - T4 Tetraiodothyronine - TBII TSH-binding inhibiting immunoglobulins - TRH TSH releasing hormone - TSAb Thyroid stimulating antibodies - TSH Thyroid stimulating hormone     

Diagnostic criteria in terminating therapy in Basedow hyperthyroidism

Hyperthyroidism due to Graves disease is characterized by the presence of Thyroid stimulating antibodies (TBI Ab). The time course of the disease shows periods of remissions followed by exacerbations. In principle, treatment with antithyroid drugs is a symptomatic therapy, although there is evidence for an influence of the underlying immunologic disease. In any case there is a need for controlled long term therapy if antithyroid drugs are used. Therefore, it is important to have criteria for the evaluation of a remission during treatment and for the prediction of continuing remission or recurrence of the disease after therapy. Among the function tests which are able to answer these questions two groups can be distinguished. The first group consists of tests for the evaluation of the thyroid feed back mechanism. This group comprises the Thyroid suppression test, the Tc-99m Uptake test (TcTU test) and the TRH-stimulation test. With exception of the TcTU test, the use of these tests is reserved for patients with antithyroid monotherapy. The other group comprises tests by which the underlying immunphenomena are examined. These tests are the TSH-receptor antibody test (TRAK), the determination of Thyroglobulin antibodies (TAK) and of microsomal antibodies (MAK). In addition, recent findings demonstrate the importance of an examination of the HLA status for therapeutical decisions. At present, the recurrence of a positive Thyroid suppression or TRH stimulation test, the normalisation of the antibodies against TSH-receptor, against Thyroglobulin and microsomal antigen as well as lacking HLA-DR 3 frequency is estimated as a strong evidence for long term remission of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gleichzeitige Bestimmung des thyreotropen Hormon- und „Long-Acting Thyroid Stimulator“-Gehaltes im Plasma bei der Basedowschen Krankheit

Zusammenfassung Im Hinblick auf den niedrigen thyreotropen Hormongehalt im Plasma wurde zu dessen Nachweis das von Adams und Kennedy beschriebene Konzentrierungsverfahren angewendet. Im Plasma der an Basedowscher Krankheit Leidenden konnte das thyreotrope Hormon nicht nachgewiesen werden. Im Verlauf der Antithyreoidea-Therapie ist jedoch der thyreotrope Hormongehalt im Blut crhöht, und bei einem Teil der Kranken wurde gleichzeitig TSH und LATS ermittelt. Diese Versuche bestätigen, daß die beiden, die Schilddrüsenfunktion stimulierenden verschiedenartigen Stoffe gleichzeitig im Organismus erzeugt werden. Der unter Wirkung der Antithyreoidea-Behandlung erhöhte Plasma-TSH-Gehalt konnte durch Verabreichung von Trijodthyronin herabgesetzt werden. All dies beweist, daß der feed-back-Mechanismus bei der Basedowschen Krankheit normal funktioniert. Für die Praxis wird die Schlußfolgerung gezogen, daß es sich zu Beginn der Behandlung der Basedowschen Krankheit erübrigt, neben der Antithyreoidea-Therapie Trijodthyronin als Adjuvans anzuwenden, es aber zu einem späteren Zeitpunkt zwecks Verhinderung der gesteigerten TSH-Sekretion nützlich ist, Schilddrüsenhormon als Adjuvans zu geben.

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Simultaneous determination of thyrotropic hormone and long-acting thyroid stimulator in the plasma of patients with graves' disease

Summary The thyrotropic hormone content of the plasma is low and for its determination the authors employed a concentration procedure described by Adams and Kennedy. In the plasma of patients with Graves' disease, TSH could not be detected and this finding supports the view that the overproduction of thyrotropic hormone does not play any role in the etiology of this disease. In the course of antithyroid treatment the TSH content of the plasma increased and in some of these patients long-acting thyroid stimulator could be detected simultaneously. According to these experiments TSH and LATS, the two thyroid stimulating substances, might be produced concurrently. The elevated TSH content of the plasma following antithyroid therapy could be decreased by the administration of 1-triiodothyronine and evidence is presented, that the feed-back mechanism is normal in Graves' disease. It is concluded that triiodothyronine treatment is not necessary at the beginning of antithyroid therapy, but that at a later stage adjuvant thyroid hormone administration is recommended to suppress increased TSH secretion.

     

Reflections on the therapeutic goal in Basedow hyperthyroidism

The present state of knowledge of the patho-etiology of autoimmune-hyperthyroidism (Graves' disease) enables us to design a therapeutic strategy basing on causal events of the autoimmune disease and aiming at complete restoration, considering the pros and cons of conservative (antithyroid drug) and destructive (surgery and/or radioactive iodine) therapy. Summarizing the arguments it is stated that antithyroid drugs are the therapy of first choice in Graves' disease, there are, however, no parameters available to predict firmly relapse in hyperthyroid Graves' disease and to establish duration of antithyroid drug treatment. For patients with hyperthyroid Graves' disease recurring after long term antithyroid drug treatment ablation of the thyroid gland as target organ of the autoimmune disease is advocated; requirements for this decision are discussed.     

Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism

BACKGROUND. Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS. The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS. The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.     

Autoantibodies highly increased in patients with thyroid dysfunction

To evaluate the significance of antithyroid antibodie levels, five hundred and twenty-six patients with thyroid diseases and 292 health subjects from Yuci district, Shanxi province, China, were studied. Serum levels were determined for thyroid hormone receptor antibody （TRAb）, microsomal antibody （TMAb） and thyroglobulin antibody （TGAb）. Among patients, the percentages for nodular goiter and thyroid adenoma, Graves＇ disease, and Hashimoto＇s thyroiditis are 44.1%, 19.6% and 17.7%, respectively. The ratios of female to male were 2.0 to 15.6. Antibody-positive patients for TMAb, TGAb and TRAb were detectable as 94.6%, 76.3% and 20.4% for Hashimoto＇s thyroiditis, and 40.0%, 30.0% and 90.3% for Graves＇s disease. In conclusion, the high levels of the TRAb in Graves＇ disease, and those of the TGAbFFMAb in Hashimoto＇s thyroiditis and idiopathic hypothyroidism are meaningful for characterizing the epidemiological basis of the diseases and for using as prognostic indicators for the relapse in individual patients. Cellular ＆ Molecular Immunology.     

Increase in serum levels of autoantibodies after attack of seasonal allergic rhinitis in patients with Graves' disease

BACKGROUND: The prevalence of allergic disease is increasing worldwide, but its influence on the clinical course of autoimmune diseases is unknown. OBJECTIVE: The purpose of this study was to assess the effect of seasonal allergic rhinitis on the clinical course of Graves' disease, which has been considered a Th2-dominant autoimmune disease. METHODS: Ten patients with Graves' disease, who were considered to be in a state of remission or near remission, were serially examined for 18 months starting from August. Five of them had seasonal allergic rhinitis due to Japanese cedar pollen, and the remaining patients had no such allergic disorders. Peripheral eosinophil counts, serum concentrations of cedar-pollen-specific IgE, anti-TSH-receptor antibody, anti-thyroid-peroxidase antibody and antithyroglobulin antibody were assessed at 2- to 4-month intervals. Serum thyroid hormones and TSH levels were also measured to evaluate disease activity. RESULTS: All patients with pollinosis had attacks of allergic rhinitis caused by cedar pollen in early March. Subsequently, peripheral eosinophil counts, pollen-specific IgE activity and serum levels of anti-thyroid-peroxidase and antithyroglobulin autoantibodies markedly increased. Serum levels of anti-TSH-receptor antibody increased in 3 patients in association with an increase in serum thyroid hormones but were always negative in 2 patients. The control patients without pollinosis showed no consistent change of these parameters. CONCLUSIONS: Seasonal allergic rhinitis aggravated the clinical course of Graves' disease and induced an increase in serum antithyroid autoantibody concentrations as well as an increase in pollen-specific IgE concentration. These data suggest that environmental antigens induce not only local allergic reactions, but also stimulate thyroid immune reactions toward Th2 proliferation, and finally aggravate Th2-dependent autoimmune thyroid disease.     

Human lymphocyte antigens (HLA) and Graves' disease in Turkey

To evaluate the association of HLA types with Turkish patients with Graves' disease, HLA typing, clinical findings, and thyroid antibodies were correlated. The HLA types, clinical findings (ophthalmopathy and age at onset), and thyroid stimulating hormone (TSH) receptor (TRAb) and antithyroid microsomal antibodies (MAb) were analyzed. Seventy Turkish patients with Graves' disease and 306 control subjects were assessed. Serological HLA typing was performed in HLA A, B, C, DR, and DQ loci. There was a significantly increased prevalence of HLA B8, B49, DR3, DR4, and DR10 in Graves' disease. The association of Graves' disease with HLA DR3 was found to be less strong than previously described. The HLA DR4 antigen may contribute to the predisposition of Graves' disease in Turkey. The results suggest that HLA B7, B13, DR7, DQw2, and DQw3 may confer a protective effect for Graves' disease in Turkey. Patients carrying HLA B12, B18, and B44 haplotypes had a tendency to develop the disease at a later age. The difference from the other studies may be the result of the selection of the controls; in part, of the variability in serological typing reagents; and, also, of the rather weak HLA associations with the disease.This study was presented in part at the Annual Meeting of the National Endocrinology and Diabetes Association, Bursa, Turkey, May 25–28, 1992.     

Antithyroid drug-induced immunomodulation in Graves' disease patients

The study was so designed as to determine the effect of low to medium daily doses of methimazole (10-20 mg per day) on the number and function of different types of immunocompetent cells in peripheral blood of patients with Graves' disease administered methimazole for the treatment of hyperthyroidism. The study included 127 patients with Graves' disease divided into three groups: group I of 29 thyrotoxic patients before the beginning of treatment; group II of 73 euthyroid patients under antithyroid treatment; and group III of 25 patients who remained euthyroid 8 weeks after therapy discontinuation. In group I, the proportion of CD4+ cells, proportion and number of granulocytes, and their ingestion and microbicidity as well as monocyte phagocytic activity and ingestion were decreased. The mentioned alterations were concluded to most likely be the consequence of the underlying autoimmune process. In group II, the proportion and number of CD8+ cells were increased, while the natural killer cell activity was impaired. Granulocyte microbicidity was suppressed as compared to group I, while the granulocyte phagocytic activity was impaired as compared to normal values. Compared to normal, monocyte microbicidity and phagocytic activity were also suppressed. Monocyte ingestion was suppressed as compared to groups I and III, regardless of the patients' thyroid hormone status. Study results strongly support the hypothesis of a direct immunosuppressive effect of methimazole in patients with Graves' disease rather than the theory favoring concomitant immunomodulation due to thyroid hormone decrease.     

Follow-up and long-term results of radioiodine therapy in immune hyperthyroidism

Follow-up and long-term results of 131-I treatment in Graves' disease are mainly influenced by the initial therapy. In Austria 131I-dose is estimated mostly as a result of thyroid uptake and volume, with the aim to restore euthyroidism. Methimazole or Propanolol pretreatment is performed in more than half of the patients. In Salzburg fixed dosis of 185 MBq 131-I are delivered until euthyroidism is achieved. Follow-up is done in 3 to 6 monthly intervals, later on once a year. Long-term results of 131-I-therapy are rare, because of the difficulty in discriminating Graves' disease from hyperthyroidism due to thyroid autonomy in the years before antibodies could be evaluated. Results are also quite uncertain, when obtained before the age of TSH- and TRH-test, because mild hyperthyroidism and hypothyroidism might have been overlooked. Early hyperthyroidism after 131-I-treatment can occur in 7% to 40% within the first year, raising with 2% to 5% each year. Hypothyroidism seems to depend on the dose, but may be caused even by low doses. This difficulty in finding the "ideal" dose might be due to stimulating, blocking and destroying antibodies with differences in the sensitivity of the thyroid tissue. The goal should be, to attain euthyroidism by radioiodine therapy, but hyperthyroidism should not be prolonged over a long period by delivering too small doses in order to avoid hypothyroidism.     

Struma resection in Basedow hyperthyroidism

The presented data show that thyroid surgery for Graves' Disease had a high therapeutic efficiency in more than 500 own patients. Considering our actual knowledge about the pathogenesis of Graves' Disease it is obvious that inadequate results of surgery are mostly due to surgical technique, which is not radical enough. Therefore subtotal bilateral thyroidectomies leaving remnants of only 4-6 g are recommended. Even as adequate premedication has shrunk the lethality of surgery to 0--which is especially significant concerning the previously dreaded postoperative thyroid storm--complications such as vocal chord paralysis and tetany do occur in a few percent. These complications, however, can usually be controlled as well as the frequent postoperative hypothyroidism. Overall thyroid surgery for therapy of Graves' Disease seems the method of choice for the treatment of younger patients with considerable thyroid enlargement and with insufficient response to antithyroid drugs.     

Thyroid-stimulating antibodies in patients with long-term remission of Graves' hyperthyroidism

Summary The persistence of TSH receptor antibodies in Graves' disease despite the remission of hyperthyroidism has been described. Our study was designed to evaluate whether this extends to functionally active stimulators of the thyroid, since the occurrence of thyroid-stimulating antibodies (TSAb) in a euthyroid patient could well have important implications on our understanding of the pathogenetic role of such autoantibodies. Forty-four patients with a previous history of Graves' hyperthyroidism were reexamined after having been in long-lasting remission for 3 to 35 years (mean 8 years). Of the patients 16 had been treated by radioiodine, 17 by surgery, and 11 exclusively by antithyroid drugs. The determination of TSAb was based on T3 release from thyroid tissue in vitro to document the final response to these immunoglobulins. TSH-binding inhibiting immunoglobulins (TBII) were evaluated by a radioreceptor assay.TSAb were highly elevated in three of the 44 patients. These three patients showed a normal TSH response to i.v. TRH, suffered from endocrine ophthalmopathy, and had been treated by radioiodine for hyperthyroidism. TBII were found positive in seven patients including the three patients mentioned. The majority of patients positive for TSAb or TBII had been treated by radioiodine and none exclusively by antithyroid drugs.In conclusion, not only TBII but also T3 release-stimulating antibodies may occur in a minority of patients with long-term remission of Graves' hyperthyroidism. However, an absence of hyperthyroidism in these patients despite the presence of such thyroid stimulators seems to be only possible in association with a lack of functional responsiveness of the target organ due to previous administration of destructive therapies. Moreover, a major role of TBII in the absence of TSAb representing stimulatory inactive autoantibodies to the maintenance of remission was not apparent.Abbreviations cAMP cyclic adenosine monophosphate - T3 triiodothyronine - T4 tetraiodothyronine - TBII TSH-binding inhibiting immunoglobulins - TRH TSH-releasing hormone - TSAb thyroid-stimulating antibodies - TSH thyroidstimulating hormone     

Laboratory based study of undetectable thyroid stimulating hormone.

The clinical importance of an undetectable thyroid stimulating hormone (TSH) concentration (less than 0.2 mU/l) was studied in a consecutive series of 2573 requests for routine thyroid function tests. Two hundred and seventeen (8.4%) patients had an undetectable TSH concentration, and of these 39 (18%) had otherwise normal thyroid hormone concentrations and no history of thyroid disease. In a follow up study 71 patients (34 outpatients and 37 inpatients) with undetectable TSH concentration associated with otherwise normal thyroid hormone concentrations were randomly selected during routine reporting of thyroid function test results. None of these patients had a history of thyroid disease. Sex hormone binding globulin concentrations were increased in five out of 50 of these patients and antithyroid antibodies were detectable in four out of 49, suggesting that in most cases the isolated undetectable TSH concentration was not associated with thyroid dysfunction, particularly hyperthyroidism. Isolated undetectable TSH concentration was observed in both inpatients and outpatients and was not associated with any particular clinical condition. Repeat specimens were received in 54 of the 71 patients and TSH concentration remained persistently undetectable in 35 of these.     

Prediction of the course of Graves' disease after medical antithyroid treatment

The course of thyrotoxicosis in 33 patients with Graves' disease was evaluated clinically and biochemically (free thyroxine index, serum triiodothyronine, thyroid stimulating antibodies, (TSAb), thyroid stimulating hormone binding inhibiting immunoglobulins (TBII)). Relapse of the disease was found to be correlated to anamnestic information of thyrotoxicosis among first degree relatives (predictive value 90%) and to concomitantly raised levels of TSAb and TBII at the start of treatment (predictive value 71%). Mean duration of treatment of patients with long-lasting remission was 16.8 months. When comparing various information used to predict relapse of Graves' disease, anamnestic information of familial predisposition to thyrotoxicosis carries the highest predictive value.     

Production of and response to interleukin-2 in Graves' disease

Interleukin-2 is a lymphokine which is believed to play a central role in the regulation of the immune response. The production of and response to interleukin-2 were determined in hyperthyroid Graves' patients together with thyroid function and serum thyrotropin receptor antibody, a marker of autoimmune activity. Interleukin-2 production by mitogen-induced peripheral blood mononuclears was markedly low in 24 of 29 patients when compared to controls. Five patients in remission had normal values. In nine patients followed during antithyroid drug therapy, interleukin-2 production returned gradually to normal levels within 4–6 months. This rise and the concomitant decrease in serum thyrotropin receptor antibody correlated with the decline in the free thyroxin index. Antithyroid drugs and triiodothyronine had no effect on interleukin-2 productionin vitro. Mitogen-activated mononuclears from hyperthyroid Graves' patients did not proliferate as well as the controls in response to interleukin-2. However, seven patients treated with antithyroid drugs and three in remission responded normally. Flow cytometry using anti-Tac antibody revealed that the interleukin-2 receptor density on mononuclears from five patients was low. This parameter was normal in treated patients and those in remission. We conclude that the production of and response to interleukin-2 by peripheral blood mononuclears from hyperthyroid Graves' patients are poor, the latter being due to impaired receptor expression. Both aberrations are restored to normal by antithyroid drug therapy or in remission. The relative roles of the autoimmune process and thyroid function in modulating the interleukin-2 pathway and the question of whether antithyroid drugs act directly or through thyroid inhibition remain to be clarified.     

Diagnosis and therapy of Basedow hyperthyroidism. Results of an Austrian study

After organisation and presentation of an European survey about "The management of Hyperthyroidism due to Graves disease" by the European Thyroid Association (ETA) national studies have been proposed. The Austrian survey was realized by the Austrian Society of Nuclear Medicine (ONG). Based on the original questionnaire of the ETA with a simple case report of uncomplicated Graves' disease and with 8 variations of the basic case including sex, age, thyroid volume and recurrence participants were asked to comment diagnostic and therapeutic procedures. Out of 42 participants 19 were heads of departments, 19 assistants and 4 internal specialists in practice with main clinical work in the field of thyroid diseases. Thyroid scintigraphy is performed in 98% (Tc 99 m 78%, J 123 15%) and ultrasound in 64%. "In vitro"-procedures include 5-6 tests (means = 5,7). 21% prefer determination of total hormones, 31% of free hormones. Various combinations of both hormone determinations are used most frequently. TRH-Test ist performed in 52.4%. Auto-antibodies are measured in 81%. TSH-receptor auto-antibodies and microsomal and thyreoglobulin auto-antibodies as well are determined in 40%. Therapeutic options of the basal case report and the 8 variations showed antithyroid drugs (ATD) in 62%, radioiodine (RI) in 26% and surgery in 12%. RI is proposed in elder patients (79%) and in patients with recurrence of the disease (45%). Surgery is recommended in patients with large thyroid volume (57%). For ATD administration only carbimazole and methimazol in a mean dosage of 60 mg/die (range 20-120 mg/die) is chosen. After euthyroidism is reached ATD is reduced to 50-90% of the original dosage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased serum PIVKA-II levels in hyperthyroidism]

PIVKA-II has been practically used as a tumor marker of hepatocellular carcinoma. On the other hand, increased serum PIVKA-II concentration was reported in a Japanese patient who had hyperthyroidism without liver diseases. To evaluate whether thyroid hormone is related with serum PIVKA-II, we examined serum PIVKA-II concentrations in patients with various thyroid diseases. Eight patients with Hashimoto disease, 24 patients with Graves' disease, and 8 healthy subjects were studied. There was no significant difference of serum PIVKA-II levels among the three groups. However, serum PIVKA-II concentrations(mean +/- SD mAU/ml) in hyperthyroidism(37 +/- 27) were significantly higher than those in hypothyroidism(16 +/- 9) and normal controls(12 +/- 4) (p < 0.05 and p < 0.01, respectively). When hyperthyroid patients were treated by antithyroid drug or isotope, serum PIVKA-II concentrations decreased in accordance with the decrease of serum FT4 concentrations. Our data indicate that serum PIVKA-II concentration was increased in patients with hyperthyroidism, but further in vivo studies are necessary to clarify the mechanism related to increased serum PIVKA-II by thyroid hormone.     

Review of thyroid disease and recent progress in thyroid research

Major thyroid diseases and recent progress in thyroid research are reviewed, including our clinical experiences and data on genetic analysis. Of the 19,944 patients receiving care in our endocrinology and metabolism department over the past 26 years(from 1974 to 2000), there were 4,471(22.4%) patients with thyroid diseases. Of these patients with thyroid disease, 37.3% had Graves' disease, 24.1% had Hashimoto's thyroiditis, and 22.2% had a benign thyroid tumor. Male-to-female ratio for Graves' disease was 1:3.2. The precise mechanism and genetic or environmental factors underlying the onset and progression of autoimmune thyroid disease need further investigation, although recent thyroid research, especially molecular level studies, has resulted in many new insights. Our genetic analysis of patients and experimental animals with thyroglobulin(Tg) abnormalities indicated the amino acids involved in the surface electric charge were important in maintaining the solid structure of Tg and thyroid hormone synthesis in addition to tyrosine and cysteine. In three patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis or idiopathic hypothyroidism, followed by the author for 8 to 20 years, it was indicated that continued comprehensive care was needed for various episodes, even those arising from non-endocrine conditions, throughout the clinical course, although clinical and laboratory findings showed improvement of the thyroid disease itself.