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B Saller

Publications and source records attributed to B Saller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Utility of third generation thyrotropin assays in thyroid function testing.

Determination of thyrotropin (TSH) by sensitive immunometric assays is currently judged as the most sensitive and also most cost-effective first-line approach to thyroid function testing. Further improvement of assay sensitivity has led to the description of third generation TSH assays with a functional sensitivity in the range of 0.01 to 0.02 mU/l. In the present study, we analyzed interassay precision profiles of a commercially available third generation assay (ACS:180 TSH-3) and documented the critical role of the time span used for the assessment of a method's functional sensitivity. By using a standardized approach with five serum pools measured in 30 different runs across a 6-week period, functional sensitivity was calculated as 0.015 mU/l. The TSH concentrations measured by two different third generation assays (ACS: 180 TSH-3 and Elecsys TSH) in samples from healthy blood donors were highly correlated (r = 0.76, n = 252). In some samples, however, discordant results were obtained. Euthyroid reference intervals were determined as 0.30-3.68 mU/l for the ACS:180 TSH-3 assay and as 0.36-3.64 mU/l for the Elecsys TSH assay. Reevaluation of reference intervals including only TPOAb or TgAb negative samples resulted in almost the same reference ranges. Measuring TSH concentrations in various patient populations, third generation assay turned out to be advantageous in the following clinical situations. (a) In patients with mildly suppressed but well detectable TSH concentrations due to functional thyroid autonomy (0.03-0.3 mU/l), overt hyperthyroidism can be excluded by third generation TSH measurement alone without the need of additional thyroid hormone measurements; (b) in patients receiving long term suppressive T4 treatment after thyroidectomy for differentiated thyroid cancer, measurement of basal TSH by third generation assays allow accurate monitoring of hormone therapy without the need for TRH testing; (c) in most patients with severe nonthyroidal illnesses and decreased TSH levels, TSH concentrations measured by third generation assays are only moderately suppressed and can be clearly discriminated from undetectable levels in overt hyperthyroidism. In conclusion, the use of third generation TSH assays is recommended in specialized clinical laboratories frequently analyzing samples taken in one of those clinical situations.

Adult↗
PubMed1998

A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

Adult↗
PubMed1998

Effect of small doses of iodine on thyroid function in patients with Hashimoto's thyroiditis residing in an area of mild iodine deficiency.

OBJECTIVE: Several studies have suggested that iodine may influence thyroid hormone status, and perhaps antibody production, in patients with autoimmune thyroid disease. To date, studies have been carried out using large amounts of iodine. Therefore, we evaluated the effect of small doses of iodine on thyroid function and thyroid antibody levels in euthyroid patients with Hashimoto's thyroiditis who were living in an area of mild dietary iodine deficiency. METHODS: Forty patients who tested positive for anti-thyroid (TPO) antibodies or with a moderate to severe hypoechogenic pattern on ultrasound received 250 microg potassium iodide daily for 4 months (range 2-13 months). An additional 43 patients positive for TPO antibodies or with hypoechogenicity on ultrasound served as a control group. All patients were TBII negative. RESULTS: Seven patients in the iodine-treated group developed subclinical hypothyroidism and one patient became hypothyroid. Three of the seven who were subclinically hypothyroid became euthyroid again when iodine treatment was stopped. One patient developed hyperthyroidism with a concomitant increase in TBII titre to 17 U/l, but after iodine withdrawal this patient became euthyroid again. Only one patient in the control group developed subclinical hypothyroidism during the same time period. All nine patients who developed thyroid dysfunction had reduced echogenicity on ultrasound. Four of the eight patients who developed subclinical hypothyroidism had TSH concentrations greater than 3 mU/l. In 32 patients in the iodine-treated group and 42 in the control group, no significant changes in thyroid function, antibody titres or thyroid volume were observed. CONCLUSIONS: Small amounts of supplementary iodine (250 microg) cause slight but significant changes in thyroid hormone function in predisposed individuals.

Adult↗
PubMed1998

[Subtotal retroperitoneoscopic adrenal gland resection--an alternative to adrenalectomy?].

Primary adrenal tumors were removed in 24 patients by the posterior retroperitoneoscopic approach, maintaining tumor-free parts of the ipsilateral adrenal gland. These partial adrenal resections did not cause a significantly different operating time or blood loss compared to 58 complete adrenalectomies performed during the same period. All 20 patients with hormonally active tumors are biochemically and clinically cured (mean follow-up 18 months). In selected cases the retroperitoneoscopic subtotal adrenal gland resection is a safe procedure, which can potentially maintain the function of the adrenal gland's cortex.

Adrenal Gland Neoplasms↗
PubMed1997

[Unilateral neck exploration in primary hyperparathyroidism].

Within a prospective case control study from 1993 to 1996, in 85 first operations for primary hyperparathyroidism the neck exploration was ended unilaterally when an adenoma (also histologically proven) and one normally small parathyroid gland were found. Otherwise or in case of simultaneous surgery of the thyroid gland, a bilateral exploration was performed. The primary success rate with this strategy, additionally based on 69.4% correct results of cervical ultrasound, was 95.3%, with a significant saving of an average of 30 min. operating time.

Adenoma↗
PubMed1994

Systemic iodine absorption during endoscopic application of radiographic contrast agents for endoscopic retrograde cholangiopancreaticography.

Hyperthyroidism induced by contrast agents in a major problem in patients with pre-existing thyroid disease, particularly in patients with functional thyroid autonomy. The present study was undertaken to evaluate whether contrast media applied during endoscopic retrograde cholangiopancreaticography (ERCP) may result in a significant increase of serum iodine levels and thus may be associated with the risk of iodine-induced hyperthyroidism. The courses of serum concentrations of total iodine and free iodide, as well as of urinary iodine excretion, were measured in 15 patients before and up to 21 days after ERCP. During ERCP, the non-ionic contrast medium iopamidol was instilled in amounts resulting in a total iodine load of 57.4 +/- 22.8 mmol (7.3 +/- 2.9 g). In all patients, ERCP resulted in a highly significant increase in serum levels of total iodine from 0.8 +/- 0.5 to 85.2 +/- 116.9 mumol/l 4 h after application of the contrast agent. In parallel, serum iodide levels were raised from 0.06 +/- 0.04 to 5.42 +/- 6.09 mumol/l and urinary iodine excretion from 71.1 +/- 35.7 mumol/mol creatinine to 621,620.9 +/- 636,492.2 mumol/mol creatinine. Peak concentrations of serum iodine are well related to the total amount of iodine applied (p < 0.05). During follow-up, iodine levels returned to pre-exposure levels within 2-3 weeks. Levels of thyrotropin, free thyroxine, and free triiodothyronine remained unchanged during the follow-up period. In conclusion, endoscopic application of iodinated contrast agents during ERCP leads to significant increases of serum levels of total iodine and free iodide and of urinary iodine excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1993

Increased binding capacity of receptors for the epidermal growth factor in benign thyroid nodules and thyroid malignancies.

To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4 +/- 16.7 fmol/mg protein in thyroid carcinomas and 10.5 +/- 5.2 fmol/mg in the corresponding normal tissue (P < 0.05, Kd 0.84 +/- 0.26 nM, n = 11). In autonomously functioning thyroid adenomas binding capacities were 14.2 +/- 8.2 fmol/mg in the nodules and 8.9 +/- 4.8 fmol/mg in normal tissue (P < 0.01, Kd 0.73 +/- 0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Molecular heterogeneity of human chorionic gonadotropin in serum and urine from patients with trophoblastic tumors.

Many studies on the structure and function of human chorionic gonadotropin (hCG) have relied on purified hCG preparations obtained from pregnancy urine. In the present studies, in order to demonstrate possible differences between the hCG species present in serum and those released into urine, we examined serum and urinary samples derived from patients with trophoblastic tumors and of pregnancy origin by sodium dodecyl sulfate electrophoresis, isoelectric focusing, and two-dimensional electrophoresis including immunostaining with a specific hCG antibody and densitometry of the protein bands. This type of analysis was presently feasible only in patients presenting with extremely high serum levels of hCG and was therefore limited to seven patients with testicular cancers, one woman with a hydatidiform mole, and one pregnancy sample. We found marked differences in the isoelectric focusing pattern between urinary and serum hCG samples, with the urinary hCG consisting of more alkaline pI variants than that present in the serum of the same patients. Tumor hCG differed from pregnancy hCG in that it contained more acidic variants, and this was true for urinary and serum-derived materials. In some tumor and pregnancy samples an hCG immunoreactive material of lower molecular weight than hCG itself was found. In conclusion, the present studies, extending previous findings on the microheterogeneity of hCG, indicate that serum and urinary-derived hCG may differ in the composition of the isoform spectrum, as does tumor and pregnancy hCG. Further, in some patients hCG immunoreactive molecules exist that differ markedly from hCG in size and charge. These observations suggest that, whenever possible, serum-derived hCG materials should be used to define the molecular structure of hCG and assess its biological activities.

Adult↗
PubMed1993

Clinical use of HCG and hCG beta determinations.

Recent advances in our understanding of hCG/hCG beta synthesis by trophoblastic and nontrophoblastic tissues together with improved techniques for measuring hCG have helped to define the role of hCG as a clinical marker. HCG determination by sensitive immunometric assay enables detection of hCG immunoreactivity in normal men and women. It facilitates early detection of normal pregnancy and significantly contributes to the diagnosis of various pregnancy-related disorders, such as ectopic pregnancy, spontaneous abortion, hydatidiform mole, choriocarcinoma or Trisomy 21. Further, determination of this marker is immensely helpful to guide curative intervention in testicular cancer. For diagnosis and follow-up of patients with testicular cancer, a method measuring both hCG and hCG beta or separate methods for each component are recommended, because a significant portion of seminoma exclusively secrete free hCG beta. Also, hCG beta production by other than trophoblastic malignancies has been well recognized. A possible clinical use of hCG beta as a marker of cancers of the bladder, pancreas or biliary tract is currently debated.

Biomarkers, Tumor↗
PubMed1992

Cross-reactivity of a commercial chemiluminescence immunoassay for human chorionic gonadotropin with the free beta-subunit.

An enhanced chemiluminescence immunoassay for the determination of serum human chorionic gonadotropin (HCG) in specimens from oncology patients has been assessed with respect to its cross-reactivity with the free HCG beta-subunit (HCG-beta). The assay, standardized against the First International Reference Preparation 75/537, had a cross-reactivity with the free beta-subunit of 625% (molar basis). Therefore this assay achieves high sensitivity for the detection of either intact HCG or free HCG-beta in serum of patients with seminomatous or nonseminomatous testicular cancers. Results of both assays, the in-house immunoradiometric assay (+HCG-beta) and the Amerlite HCG-60 assay, showed a close correlation (R = 0.854-0.960) when serum samples from tumour patients were analyzed. Moreover, the content of free beta-subunit determined in a specific HCG-beta assay, could be quantitatively measured in the enhanced chemiluminescence immunoassay. Thus, this assay is suitable for oncology use, but also highlights the limitations of measuring HCG in serum samples.

Antibodies, Monoclonal↗
PubMed1991

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.

The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

Adult↗
PubMed1991

Course of thyroid iodine concentration during treatment of endemic goitre with iodine and a combination of iodine and levothyroxine.

In the treatment of endemic goitre, the concept of giving levothyroxine in combination with iodine offers a promising therapeutic approach by influencing not only TSH secretion but also intrathyroidal iodine content. However, little is known about the doses of iodine necessary to correct intrathyroidal iodine deficiency. To get more information on this important issue, we conducted a prospective, double-blind study on the effect of a monotherapy with 500 micrograms iodide/day and a combined treatment with 100 micrograms levothyroxine and 100 micrograms iodide/day on thyroid iodine concentration as measured by fluorescence scintigraphy. In a group of 12 patients, a 4-month treatment with 100 micrograms levothyroxine and 100 micrograms iodide/day did not significantly affect thyroid iodine concentration (0.35 +/- 0.14 vs 0.37 +/- 0.11 mg/g). The application of 500 micrograms iodide/day in these patients during a second 4-month period resulted in a sharp increase in thyroid iodine concentration from 0.37 +/- 0.11 to 0.61 +/- 0.14 mg/g (p less than 0.01). Another group of 8 patients first treated with 500 micrograms iodide/day also showed a significant increase in iodine concentration from 0.35 +/- 0.14 to 0.65 +/- 0.20 mg/g (p less than 0.01). After switching to the combination regimen during a second 4-month period, thyroid iodine concentration slightly decreased, particularly in those patients with high iodine concentrations after monotherapy with iodide (0.65 +/- 0.20 vs 0.50 +/- 0.12 mg/g, p less than 0.05). In conclusion, treatment with 500 micrograms iodide/day could sharply increase thyroid iodine concentration in patients with endemic goitre. In contrast, a combination of 100 micrograms levothyroxine and 100 micrograms iodide/day had no significant effect on thyroid iodine concentration.

Adult↗
PubMed1990

Evaluation of the ratio of T3 release stimulating antibodies to TSH-binding inhibiting antibodies during the course of Graves' disease.

The mechanisms leading to a remission of Graves' hyperthyroidism are still unknown. One possibility would be that autoantibodies raised during the course of disease could change the composition of the autoantibody spectrum in such a way to counterbalance the action of stimulatory autoantibodies, thereby resulting in an induction of remission. Therefore, in the present study using a rigorous methodological approach we have characterized the portion of T3 release stimulating autoantibodies among the total body of TSH receptor antibodies, i.e. the TSAb/TBII ratio, over the course of a 12 month antithyroid therapy in 25 patients with Graves' hyperthyroidism. Further, we have evaluated the relation of the alteration of the antibody spectrum to the course of disease. The TSAb/TBII ratio was indeed found to be subject to considerable changes. The observed shift in the antibody composition was more often in favor of a relative increase in stimulatory inactive TBII. Nevertheless, the clinical course of patients showing a persistence of TBII despite the decline or even absence of TSAb proved to be variable. In conclusion, our data indicate that the spectrum of autoantibodies may change over the course of antithyroid therapy owing mostly to a relative rise in stimulatory less active autoantibodies. This phenomenon, however, is apparently not closely related to the course of disease.

Adult↗
PubMed1990

Testicular cancer secretes intact human choriogonadotropin (hCG) and its free beta-subunit: evidence that hCG (+hCG-beta) assays are the most reliable in diagnosis and follow-up.

Human choriogonadotropin (hCG) and free hCG-beta values for 934 serum samples from patients with seminomatous or nonseminomatous testicular cancer were measured by highly specific immunoradiometric assays (IRMAS). In non-seminoma samples, hCG and hCG-beta were highly correlated (r = 0.82, P less than 0.001). Of 112 "marker-positive" seminoma samples, only 46 (41.1%) showed both increased hCG and hCG-beta. In 39 cases (34.8%) only hCG-beta and in 27 cases (24.1%) only dimer-hCG was increased. This makes the determination of hCG and hCG-beta, either by two assays or by a single hCG (+hCG-beta) assay, most reliable in these patients. For all samples, hCG (+hCG-beta) was measured by a polyclonal RIA and a monoclonal IRMA, which differed in their cross-reactivities with hCG-beta (234% and 720%, respectively). The hCG (+hCG-beta) IRMA, as a result of its higher hCG-beta cross-reactivity, was superior to the hCG (+hCG-beta) RIA in detecting slightly increased hCG-beta. Additionally, 11 widely used commercial hCG kits were tested for their hCG-beta cross-reactivities and showed values between less than 3% and 264%.

Antibodies, Monoclonal↗
PubMed1989

Insulin and insulin-like growth factor (IGF I) modulate the effects of bTSH on 3H-thymidine incorporation in human thyroid cells in primary culture.

The role of TSH in thyroid cell growth and the pathogenesis of goiter has become a matter of recent debate, since many investigators have failed to demonstrate a growth-promoting effect of TSH in human thyroid cells in culture. While those studies have focused on the action of TSH in human thyroid cells, the influence of assay conditions and cofactors has received scant attention. In the present study, we have therefore undertaken to elucidate the effects of insulin and insulin-like growth factor (IGF I) on 3H-thymidine uptake in human thyroid cells, particularly with respect to their relation to the actions of bTSH. We could demonstrate a considerable, dose-dependent stimulation of 3H-thymidine incorporation in the cells by bTSH that was dependent on the presence of insulin or IGF I; bTSH alone was ineffective in that respect. The concentrations of insulin and IGF I required to facilitate the TSH response were of a magnitude at which both peptides were totally ineffective by themselves. At concentrations of insulin or IGF I that produced a maximum stimulation of 3H-thymidine incorporation, the addition of bTSH did result in a slight decrease rather than a further increase of that stimulation. We conclude from these findings, first, that TSH appears to be a growth factor for human thyroid cells under the conditions described, and, second, the effects of TSH on thyroid cell proliferation are under the control of cofactors like insulin and IGF I.

Cell Division↗