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Biomedical subjects

O Eber

Publications and source records attributed to O Eber.

At least 19 recordsLinked to original sources

Subclinical hyperthyroidism as a risk factor for atrial fibrillation.

OBJECTIVES: Atrial fibrillation is a well-known manifestation of hyperthyroidism. We studied whether subclinical hyperthyroidism with low serum thyrotropin concentrations and free thyroid hormone concentrations within the normal range in clinically euthyroid persons is a risk factor for subsequent atrial fibrillation. METHODS: We studied 23,638 persons. The subjects were classified according to their serum thyrotropin concentrations: group 1 comprised those with normal values of serum thyrotropin concentration (>0.4-5.0 mU/L) and free tri-iodothyronine and free thyroxine concentrations were within the normal range (22,300 subjects), group 2 comprised those with both low serum thyrotropin values (</=0.03 mU/L) and elevated free tri-iodothyronine and free thyroxine concentrations (725 subjects), and group 3 comprised those with low values of serum thyrotropin (<0.4 mU/L) and free triiodothyronine and free thyroxine concentrations were within the normal range (613 subjects). RESULTS: Atrial fibrillation was present in 513 persons (2.3%) in group 1 with normal values for serum thyrotropin, 100 (13.8%) in group 2 with overt hyperthyroidism, and 78 (12.7%) in group 3 with subclinical hyperthyroidism. The prevalence of atrial fibrillation in patients with low serum thyrotropin concentrations (<0.4 mU/L) was 13.3% compared with 2.3% in patients with normal values for serum thyrotropin (P <.01). The relative risk of atrial fibrillation in subjects with low serum thyrotropin and normal free tri-iodothyronine and free thyroxine concentrations, compared with those with normal concentrations of serum thyrotropin, was 5.2 (95% CI 2.1-8.7, P <.01). CONCLUSION: A low serum thyrotropin concentration is associated with a >5-fold higher likelihood for the presence of atrial fibrillation with no significant difference between subclinical and overt hyperthyroidism.

Atrial Fibrillation↗

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.

Adult↗

Thyrotropin and thyroglobulin as an index of optimal iodine intake: correlation with iodine excretion of 39,913 euthyroid patients.

The recommendations for the dietary allowance of iodine are 150 micrograms per day for adolescents and adults. Thyrotropin (TSH) and thyroglobulin (Tg) can be used as surveillance indicators for assessing iodine deficiency disorders. We compared the relation between TSH and Tg, free triiodothyronine, and thyroxine serum levels with urinary iodine excretion in 2311 untreated euthyroid patients using our modified cericarsenite method. An adequate iodine intake may be assumed when TSH and Tg values are at the lower end of the normal range. Patients were grouped according to urinary iodine excretion and goiter size. In the group with an iodine excretion between 201 and 300 micrograms of iodine per gram of creatinine, the lowest TSH values and even low Tg levels could be shown. We conclude that an iodine intake of approximately 250 micrograms/day is associated with the lowest TSH stimulation to thyrocytes. In the groups separated according to thyroid size, significantly higher Tg levels were found in the patients with uninodular and multinodular goiter as a result of longstanding iodine deficiency, whereas actual urinary iodine excretion did not differ significantly. Additionally, iodine excretion of 39,913 euthyroid patients between 1984 was 1996 was examined. In Austria iodized salt (10 mg KI/kg) was introduced by law in 1963 and increased to 20 mg KI/kg salt in 1990. An initial increase of iodine excretion until 1993 was followed by a decrease in 1994 and 1995 without further changes in 1996. These results show that iodine intake has improved since 1984; however, in 1996 iodine excretion in one-third of the investigated patients was under 100 micrograms per gram of creatinine and more than 80% had less than 200 micrograms per gram of creatinine.

Adult↗

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

Adolescent↗

[Point mutations of the thyrotropin receptor gene in autonomously functioning thyroid gland nodules: correlation with clinical findings and morphology].

Seventeen autonomously functioning thyroid nodules (AFTN) were analyzed for the most frequent mutations of the thyrotropin (TSH) receptor gene at codons 619, 631, 632 and 633. DNA was extracted from formalin-fixed, paraffin-embedded samples from both nodules and surrounding tissue after micro- or macrodissection. A fragment of the TSH receptor gene (bp 1762-1976) encoding the third cytoplasmic loop and the sixth transmembranous domain was amplified by PCR. Screening for mutations at codons 619, 631, 632 and 633 was performed by restriction enzyme analysis using Asp 718, Hph I, Taq I and EcoR I, respectively. For verification, cases with a mutated restriction site were cloned and sequenced. Mutations were found in 3 AFTNs (18%): in 2 cases at codon 632 and in 1 case at codon 631. The 2 cases with a mutation at codon 632 harbored additional mutations at codon 599 and 640, respectively, detected by sequencing. Normal thyroid tissue outside the AFTNs did not harbor mutant TSH-receptor. Mutations occurred in patients with clinical and subclinical hyperthyroidism. Mutations were associated both with total (2 cases) and partial (1 case) suppression of the surrounding thyroid tissue as noted on the scinti scan. AFTNs with TSH-receptor mutation occurred as single nodules. All 3 nodules with mutations were classified histologically as nodular hyperplasia according to the criteria of the WHO. Although the number of cases is small, our data suggest that AFTNs are clinically and morphologically heterogenous. Since the most common TSH-receptor mutations occur only in a small subset of AFTNs other molecular genetic alterations may be involved in the development of AFTNs.

Adenoma↗

Evaluation of the Abbott IMx ultrasensitive II hTSH immunometric assay in three European centres: a comparison with established commercial immunometric assays for thyrotropin.

The Abbott Ultrasensitive II hTSH assay was evaluated in three European centres and its performance compared with its predecessor and with commercially available kits. A total of 408 individuals was included in the study (140 euthyroid, 116 hyperthyroid and 86 hypothyroid subjects, as well as 26 patients with non-thyroidal illness and 30 patients with thyroid cancer). The kit was evaluated for (im)precision and analytical and functional sensitivity according to ECCLS-Guidelines. The analytical sensitivity lay between 0.004 and 0.013 mU/1, the mean value being 0.008 mU/1, results being from 12 runs. The functional sensitivity gave a coefficient of variation below 20% at a concentration of 0.05 mU/1 under routine conditions. Inter-assay precision was less than 7% at 0.25 mU/l (range 5.3-6.8%), less than 6% at 6 mU/l (range 4.0-5.2%) and less than 9% at 30 mU/l (range 6.5 - 8.7%). Intra-assay (im)precision was not calculated as the Abbott IMx is designed to run on singlicate determinations.

Adult↗

Changes in thyroid hormone parameters after acute myocardial infarction.

Abnormalities in circulating thyroid hormone levels are very common in systemic nonthyroidal illnesses, such as acute myocardial infarction. In this study, thyroid parameters were determined in a series of 16 consecutive infarction patients treated by thrombolysis. Blood samples were taken before therapy as well as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and triiodothyronine decreased and reverse T3 increased significantly showing no major variations up to 72 h, whereas thyroid-stimulating hormone values remained almost unchanged during the observation period. Subjects with CK-MB levels of more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in comparison to those with lower values (n = 6; NS). Thus, although hormone modifications very often occur following acute infarction, thyroid status may not serve as a marker for the extent of left ventricular dysfunction in the early phase of myocardial infarction.

Aged↗

Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease.

Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.

Adult↗

Evaluation of the Cobas Core system for use in routine diagnosis of thyroid disorders.

The aim of this clinical study was to evaluate the TSH, FT4, FT3, T3, and T4 assays designed for use on the Cobas Core Immunoassay Analyzer. Performance of these enzyme immunoassays (EIAs) was compared with well established and routinely used radioimmunoassays (RIA) or immunoradiometric assay (IRMA). In the first part of the study, the between-run and within-run data as well as the linearity of the Cobas Core assays was carried out, showing a very high precision; most coefficients of variation (CVs) were below 8%. In the second part of the study, serum samples from patients with different thyroid diseases were evaluated, and the results compared with those obtained by RIA or by IRMA. All results were highly comparable with the clinical aspects of all investigated thyroid disorders, and the data of TSH, FT4, T3 and T4 were completely in concordance with those assessed by RIA or IRMA methods; however, only the FT3 assays had a moderately correlation. In contrast to RIA methods, Cobas Core EIAs provided precise results in patients with thyroid hormone transport protein anomalies or T4/T3 autoantibodies; moreover, elevated serum concentrations of thyroxine binding globulin (TBG) did not affect measurement of total thyroid hormone concentrations.

Adult↗

[Treatment of hyperthyroidism with antithyroid drugs].

For the last 50 years the therapeutic possibilities in treating hyperthyroidism have comprised not only the reversible method of antithyroidal drugs but also the 2 irreversible methods viz. surgery and application of radioiodine. Of late beta-adrenergic blockers turned out to be an important adjuvant therapy enabling an early reduction in the hyper-sympathicomimetic condition of Graves's disease. Moreover, R-propranolol will in itself inhibit the peripheral conversion of T4 to T3. The selection of the method of choice is difficult to determine in the individual case requiring both endocrinologic knowledge and specific laboratory findings. Thanks to a striking reduction in the use of conventional antithyroid drugs it has also become possible to decrease the side effects markedly. In spite of far reaching investigations no reliable marker could be found in predicting long lasting remission following discontinuation of antithyroidal drugs. Not withstanding the enormous progress achieved in the pathogenesis and innummerable immunologic findings we are still lacking a causal therapy in treating Graves' disease.

Adrenergic beta-Antagonists↗

[Late potentials in high resolution ECG in thyroid gland dysfunction].

In this study we examined 278 patients as to the effect of thyroidal dysfunctions upon late-potential parameters in high-resolution ECG (HR-ECG). It could be demonstrated that both hyper- and hypothyroidism tend to produce late potentials. It is remarkable that even "subclinical" dysfunctions reveal significant alterations in HR-ECG. As late potentials represent a risk factor for ventricular arrhythmias these results are an additional indication that already "subclinical" dysfunctions of thyroid gland call for an appropriate therapy. In hyperthyroidism late potentials may be eliminated rapidly by propranolol even in low dosages.

Anti-Arrhythmia Agents↗

[TSH receptor double mutation in functional autonomic thyroid nodule].

TSH receptor stimulating antibodies (TSAb) are well known in the pathogenesis of Graves' disease. Recently mutations in the DNA coding for the TSH-receptor (TSHR) have been revealed in autonomously functioning thyroid nodules (AFTN). In this study we looked for mutations in 9 patients with AFTN. DNA was extracted separately from the nodules and the paranodular thyroid tissues. A fragment of the TSHR gene (bp 1762-1976) was amplified by PCR. The amplified DNA was digested with Hph I, Taq I, Kpn I and Eco RI, respectively, and the resulting fragments were analyzed by gel electrophoresis. Mutations were detected in the nodules of 3 of the 9 patients. In the nodules of 2 patients we found simultaneous mutations affecting the restriction sites of Hph I and Taq I. In the 3rd patient a mutation affecting the restriction site of Hph I was observed. The simultaneous occurrance of TSHR-mutations altering Hph I (Position 631) and Taq I (position 632) restriction sites in AFTN have not been described so far.

Adenoma↗

[Do increased lipoprotein(a) levels in euthyroid autoimmune thyroid diseases predict an increased risk of arteriosclerosis?].

Elevated serum levels of lipoprotein(a) [Lp(a)] represent an independent risk factor in the development of arteriosclerosis and coronary heart disease. In overt but also in subclinical hypothyroidism a reversible increase of Lp(a) occurs. We compared Lp(a) serum levels, cholesterol, triglyceride, HDL- and LDL-cholesterol in 19 hypothyroid patients prior to and following the state of euthyroidism (group 1). On the other hand in group 2 we investigated 20 euthyroid patients having elevated thyroid antibodies as against 50 euthyroid normolipemic control subjects without detectable thyroid antibodies. Group 1: The elevated Lp(a) serum levels of the hypothyroid patients decreased significantly in the euthyroid state (37.9 +/- 8.24 vs. 28.1 +/- 6.13 mg/dl, mean +/- SEM). Group 2: The mean Lp(a) serum levels of the patients with increased thyroid antibodies were significantly higher than those of the control group (24.8 +- 5.78 vs. 9.6 +/- 1.56 mg/dl, mean +/- SEM). In other parameters of lipid metabolism and thyroidal function no significant differences between both groups could be seen. The question arises whether such isolated Lp(a) elevation will lead to an increased arteriosclerotic risk. To minimize this possible risk regular controls of thyroid function should be carried out in euthyroid patients with elevated thyroid antibodies. In this way hypothyroidism may be detected and treated at an early stage.

Adult↗

Impact of stress and triiodothyronine on plasma magnesium fractions.

The differential regulation of free and bound plasma magnesium was studied in healthy volunteers exposed to various forms of stress, and patients screened for thyroid disorder. Both ergometric (7 min) and psychological (45 min) stress had no effect on free plasma magnesium, but increased the bound fraction. Before combined physical and psychological stress (45 min aerobatics) there was no correlation between the plasma fractions of magnesium; thereafter, there was a strong negative correlation between increased free and decreased bound magnesium. Three days of training in ground combat increased significantly the plasma levels of both magnesium fractions. Patients screened for thyroid disorder had a significant, positive correlation between both plasma fractions of magnesium, and a highly significant negative correlation between plasma T3 and the two magnesium fractions. No clear correlation between plasma catecholamines and magnesium levels was seen under any of the above conditions. Overall, the data show that the evaluation of the functions of circulating magnesium requires the specific measurement of the free and bound fractions.

Austria↗

Familial dysalbuminaemic hyperthyroxinaemia and inherited partial TBG deficiency: first report.

BACKGROUND: Abnormalities of the serum thyroid hormone binding proteins are not uncommon but, when properly assessed, they do not present diagnostic difficulties. In contrast, the presence of two inherited defects of thyroid hormone transport, of the type presented in the family described here, may cause a major problem in diagnosis and has not been described previously. METHODS: All conventional thyroid function tests were carried out. In addition, thyroid hormone binding to serum proteins was assessed by agarose gel electrophoresis, and thyroxine binding globulin by immunoassays and by immunodiffusion. The affinity of TBG for thyroxine and its maximal binding capacity were assessed by Scatchard analysis. RESULTS: Tests carried out on 22 members of the family revealed familial dysalbuminaemic hyperthyroxinaemia in 10 family subjects. All five living siblings of the propositus had familial dysalbuminaemic hyperthyroxinaemia and two tested transmitted this trait to their children and grandchildren. This was not the case with the propositus. Partial thyroxine binding globulin deficiency only, inherited presumably from the propositus' mother, was found in two family members. Both thyroxine binding globulin deficiency and familial dysalbuminaemic hyperthyroxinaemia were detected in the propositus and in his male nephew, masking the typical laboratory abnormalities associated with each of these defects. CONCLUSIONS: Coexistence of two inherited defects of thyroid hormone transport proteins produce atypical thyroid function test abnormalities, which can be misinterpreted as thyroid hormone dysfunction.

Adult↗

Postpartum thyroiditis and familial dysalbuminemic hyperthyroxinemia.

Familial dysalbuminemic hyperthyroxinemia (FDH) is a syndrome associated with euthyroidism and increased binding of T4 to serum albumin. The combined occurrence of FDH and postpartum hyperthyroidism due to Graves' disease has only been reported in one patient. We now describe the first case of FDH and thyrotoxicosis due to postpartum silent thyroiditis. In a 19-yr-old woman, FDH, suspected on the basis of strikingly elevated analog free T4 (fT4) and total T4 values, but normal two-step fT4 and serum TSH values, was confirmed by [125I]T4 agarose-gel electrophoresis. When FDH and thyrotoxicosis, characterized by markedly elevated analog fT4, total T4, and two-step fT4 values and undetectable TSH values, coexist, the differential diagnosis may be confusing.

Adult↗

The influence of iodine on the intensity of the intrathyroidal autoimmune process in Graves' disease.

Several lines of evidence support an etiological role of iodine for the initiation and perpetuation of autoimmune thyroid disease. However, varying relapse rates after increased iodine supplementation have been reported for Graves' disease. Furthermore the effects of iodine on the intensity of human autoimmune thyroiditis have previously only been investigated by indirect parameters and actions of iodine on thyroid function and a possible enhancement of the intrathyroidal autoimmune process in Graves' disease are difficult to separate in previous studies. Moreover lymphocytic thyroiditis in animal models has always been induced by considerably higher iodine doses as those used in in vivo studies. Therefore we investigated the effect of low and high iodine concentrations on the intensity of the intrathyroidal autoimmune process in Graves' disease. The intensity of intrathyroidal infiltration by lymphocytes, memory T cells, plasma cells and antigen presenting cells was determined by quantitative immunohistologic methods in 38 Graves' disease patients. 12 patients received additional preoperative iodine (group II) and 26 were treated with thiourelene antithyroid drugs only (group I). Urinary and intrathyroidal iodine concentrations were determined by a modified cer arsenite method in both groups. Application of high iodine doses in group II induced a significant increase of kappa and lambda positive plasma cells and interdigitating reticulum cells. This was not observed for activated T cells. There was no correlation between the extent of intrathyroidal infiltration by activated T cells, plasma cells and antigen presenting cells, and intrathyroidal or urinary iodine or intrathyroidal iodine concentrations in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗