[Clinical evaluation of a new thyroglobulin immunoradiometric assay in the follow-up of differentiated thyroid carcinoma]. / Klinischer Stellenwert eines neuen Thyreoglobulin-immunoradiometrischen Assays in der Nachsorge des differenzierten Schilddrüsenkarzinoms.

AIM: Formal and clinical comparison of a new 3 (rd) -generation-Tg-IRMA (3-G-IRMA; Dynotest Tg-plus) with a conventional Tg-IRMA (3-G-IRMA; SELco Tg-assay) for patients with differentiated thyroid carcinoma. In addition we evaluated, if thyroglobulin (Tg) levels above a specific threshold concentration indicate the need for further investigations for residual disease. PATIENTS, METHODS: Tg concentration of 105 sera of 93 consecutive patients with a differentiated thyroid cancer was determined with both assays and compared at different cut-off values (Dynotest Tg-plus: 0.2, 1, 2 ng/ml; SELco Tg-assay: 0.5, 1, 2 ng/ml) with the clinical results in respect to the corresponding TSH concentration. RESULTS: Tg concentration did not show any significant difference (SELco Tg-assay 0.5 ng/ml, Dynotest Tg-plus 0.2 ng/ml). The Tg-values of both assays correlated with 97%. However, correlation of recovery in both assays was small (40%). The sensitivities and specificities of both assays at different cut-offs and TSH values did not reveal significant differences. In patients with TSH concentration > 30 micro U/ml the functional assay sensitivity was superior to arbitrary cut-offs in the decision to start further evaluations. CONCLUSIONS: In our study neither formal nor clinical significant differences between two Tg-assays were found. In a hypothyroid patient (TSH > 30 micro U/ml, Tg concentration exceeding the functional assay sensitivity) further investigations for residual disease are warranted. Higher thresholds are of limited value, due to an unacceptably high rate of false negative results.

[Clinical implications of a new TSH receptor antibody assay (DYNOtest TRAKhuman) in autoimmune thyroid diseases]. / Klinische Implikationen eines neuen TSH-Rezeptor-Antikörper-Assays (DYNOtest TRAKhuman) bei autoimmunen Schilddrüsenerkrankungen.

AIM: Conventional radioreceptor-antibody-assays (RAAs) fail in the detection of TSH-receptor antibodies (TRAKs) in 10-30% of patients with Graves' disease (GD). The aim of this study was the evaluation of the diagnostic and clinical impact of a new RRA (DYNOtest TRAKhuman) which uses the human recombinant TSH-Receptor in the diagnosis of autoimmune thyroid disease. METHODS: Sera from 142 consecutive patients (GD: n = 50, autoimmune thyroiditis/AIT: n = 92) and from 55 controls (31 patients without any thyroid disease and 14 with euthyroid goiter) were evaluated both with the DYNOtest TRAKhuman-assay and a conventional RRA (TRAK-Assay). Thyroid in vitro parameters and thyroid sonography were performed in all patients. RESULTS: The DYNOtest TRAK-assay was significantly superior to the conventional RRA in the diagnosis of GD (p < 0.00012), especially in those who were treated by thionamides (p < 0.003) and in the diagnosis of TRAK-positive patients with AIT (p < 0.003). The majority of TRAK-positive AIT-patients suffered from hypothyroidism. One false positive result in patients with euthyroid goiter was found in the TRAK-Assay as well as in the DYNOtest TRAKhuman-Assay. Therefore the specificity of the DYNOtest TRAKhuman was not inferior compared with the conventional assay. CONCLUSION: The DYNOtest TRAK-assay is superior in the diagnostic work up of Graves' disease compared with a conventional TRAK-assay and offers an equal specificity.

Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function.

Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 micrograms), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.

Hyperthyroidism due to Graves' disease and due to autonomous goiter.

An attempt was made to classify 326 patients with hyperthyroidism due to Graves' disease and due to autonomous goiter in an area of endemic iodine deficient goiter using the following two sets of criteria: Primary criteria: the presence of endocrine ophthalmopathy (Graves' disease) and the absence of endocrine ophthalmopathy and the absence of microsomal antibodies greater than or equal to 1:1600 (autonomous goiter). Sixty-nine percent of the patients could be divided in the two groups with the aid of these criteria. Secondary criteria: age greater than 50 years, presence of a goiter, presence of thyroid nodules, activity distribution in the scan, iodine intake determined by iodine excretion in the urine. These criteria had to be applied in the 31% of the patients who could not be divided into one of the two groups using the primary criteria. The secondary criteria were accumulative. Using these criteria 55% of the 326 patients were classified as having Graves' disease and 45% as having autonomous goiter. The probability of correct grouping when both primary and secondary criteria were applied was estimated to be 90% compared to 54% when we used only the classical terms, i.e. endocrine ophthalmopathy and diffuse goiter on the one hand and multinodular goiter without endocrine ophthalmopathy on the other hand. In a second group of 120 hyperthyroid patients classified in this way, thyrotropin displacing activity was determined independently. Its prevalence was 79% in patients classified as having Graves' disease but only 3% in those classified as having autonomous goiter. The prevalence of TDA observed in patients who presumably had autonomous goiter was in the same range as in the following groups: 45 normal individuals; 126 patients with euthyroid goiter; and in 112 patients with euthyroid and hyperthyroid autonomous adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prognostic value of the determination of thyroid hormones]. / Der Voraussagewert von Schilddrüsenhormonbestimmungen.

For recognition and exclusion of hyper- and hypothyroidism total thyroxine, index of free thyroxine, free thyroxine and total triiodothyronine were evaluated. Among 532 strictly selected patients, corresponding to the five main thyroid out-patient groups, the four parameters were estimated simultaneously. Their sensitivity and specificity including two combinations of free thyroxine and total triiodothyronine were calculated. On the basis of an average prevalence of the five above-mentioned groups among our patients and the two most frequent interfering factors (administration of oestrogens and additional iodine intake) predictive values were assessed. The following results were obtained. 1. Differences among the various in-vitro parameters are less than generally assumed. For free thyroxine and the combination of increased free thyroxine or total triiodothyronine, sensitivity and specificity were slightly higher than for other parameters. 2. There is insufficiently substantiated probability of positive evidence of hyperthyroid and hypothyroid states being supplied by all the examined parameters if these are the only criteria relied upon. The probability of positive evidence of hyperthyroid states is only acceptable if, prior to use of in-vitro tests, the prevalence has been considerably increased by history and clinical findings. 3. The probability of exclusion of hyperthyroid states supplied by the examined parameters is high. However, despite their high negative predictive value they are insufficient for the definite exclusion of hypothyroid states if the latent types are included.