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Biomedical subjects

U Feldt-Rasmussen

Publications and source records attributed to U Feldt-Rasmussen.

36 records · Page 2Linked to original sources

Relationship between serum thyroglobulin, thyroid volume and serum TSH in healthy non-goitrous subjects and the relationship to seasonal variations in iodine intake.

In order to investigate the interrelationship between serum thyroglobulin (Tg), thyroid volume and serum TSH by a sensitive method, 176 healthy euthyroid non-goitrous subjects were studied. Furthermore the seasonal influence, assuming seasonal differences in iodine intake in Denmark, was studied in 13 healthy male volunteers. A weak correlation between serum Tg and thyroid volume was found only in female non-goitrous subjects. No correlations between serum Tg, thyroid volume, free T4 and free T3 indices, T3/T4 ratio, serum TSH by sensitive method or age were seen. Thyroid volume was increased (P less than 0.01) during the winter without any change in thyroid function or TSH level, whereas serum Tg level in these subjects was significantly lower (P less than 0.02) during the winter compared with the summer. In conclusion, serum Tg showed no correlation with either thyroid volume, super-sensitive TSH or thyroid function in a population of non-goitrous subjects in Denmark. The lack of correlation between increased thyroid volume and decreased serum Tg during the winter compared with the summer is unexplained. It might be hypothesised that short-term changes in iodine intake induce only colloid accumulation (i.e. increased thyroid volume) without changes in the glandular secretion of Tg or thyroid hormones.

Adolescent

Thyroid function in patients with Pendred's syndrome.

Thyroid function was studied in 17 unrelated patients with Pendred's syndrome. Fourteen patients had been treated with L-thyroxine, which was withdrawn during the investigation. Eight of the patients had previously had a thyroid resection. Thirteen patients had goiter at the time of study. The serum total thyroxine and serum total triiodothyronine concentrations were normal in 8, of whom 3 had elevated serum TSH concentrations. In the remaining 9 cases the thyroxine levels were below normal with elevated TSH. Serum reverse triiodothyronine concentrations were decreased in 8 out of 11. Median serum thyroglobulin was 973 micrograms/l (range 10.9-3200 micrograms/l) and increased in 13. Three patients had slightly positive thyroglobulin antibodies and one with normal level was thyrodectomized. Thyroid stimulating antibodies as measured by adenylate cyclase stimulation (median 114%, range 85-137%) were slightly increased in 11. When measured as TSH binding inhibiting immunoglobulins none were positive. Thyroid microsomal antibodies were negative in all. All patients with a detectable 131I uptake (n = 15) showed a pathological iodide perchlorate discharge test (median 32%, range 16-46%). These findings indicate an organification defect with impaired hormone synthesis.

Adolescent

European interlaboratory comparison of serum thyroglobulin measurement.

A European interlaboratory comparison of serum thyroglobulin measurements was performed after an initiative from the European Organization of Research and Therapy of Cancer. Fifty-two laboratories were addressed and 45 of these (83%) participated in the study by measuring serum thyroglobulin and its autoantibody in 5 thyroglobulin containing sera. Thyroglobulin antibodies were added to two of the sera. Two commercial kits were used by a large number of the laboratories (11 and 8, respectively). Each kit showed a reasonably low interlaboratory coefficient of variation at concentrations above 25 micrograms/l, but with discrepancy between the methods. The remaining miscellaneous methods (24) showed a variation above 65% in all samples. In all laboratories the addition of thyroglobulin antibodies resulted in false thyroglobulin measurements with either elevated or depressed levels. It is concluded that a reference calibrator for serum thyroglobulin is strongly needed as the first essential step towards interlaboratory standardization of serum thyroglobulin, thereby opening a possibility for multicentre studies of its value in the post-therapy follow-up of patients with differentiated thyroid carcinoma.

Clinical Protocols

Interleukin-1 affects the function of cultured human thyroid cells.

Cytokines are peptide hormones essential for cellular communication in the immune response. The purpose of this study was to investigate the influence of cytokines, especially recombinant interleukin 1 beta (rIL-1 beta), on human thyroid cells. Thyroglobulin (Tg) was measured by a double antibody radioimmunoassay, and cyclic AMP (cAMP) by a competitive protein binding assay. Supernatants from unstimulated and phytohaemagglutinin-stimulated blood mononuclear cells were added to human thyroid cells cultured in monolayers. A dose-dependent inhibition of the secretion of Tg and cAMP was demonstrated. Both subcultured and primary cultured cells incubated with rIL-1 beta at pharmacological levels (10(-1)-10(2) U/ml) exhibited an inhibition of Tg and cAMP secretion, while at physiological levels (10(-5)-10(-3) U/ml), the secretion of Tg was enhanced. The similar stimulation of cAMP was demonstrated in subcultures. These in vitro studies suggest that IL-1 beta may play a role in the pathogenesis of autoimmune thyroid diseases. Further, the stimulations at low concentrations indicate that IL-1 beta may regulate the function of the thyroid gland under physiological conditions.

Autoimmune Diseases

Lacking evidence for release of thyroid hormones from circulating thyroglobulin during subtotal thyroidectomy.

The effect of subtotal thyroid resection for thyrotoxicosis on concentrations of serum thyroid hormones and thyroglobulin (Tg), was determined in 10 patients during operation and the subsequent 18 days. Mean serum Tg responded drastically, increasing from a pre-operative value of 0.30 nmol/l to a peak value of approximately 26 nmol/l during operation followed by a gradual decline to levels lower than before surgery on day 18. Mean serum total thyroxine was 114 nmol/l pre-operatively and free thyroxine index (FT4I) 105 units. Both fluctuated only slightly during operation. Postsurgically, the mean values decreased to below 50% of the pre-operative level. Mean serum total triiodothyronine (TT3) was 1.46 nmol/l pre-operatively. It decreased during operation, reaching a nadir of 0.55 nmol/l on day 2, whereafter the concentration increased slightly. Mean serum reverse T3 (rT3) was 0.45 nmol/l pre-operatively, increased 62% during surgery, and decreased postsurgically. The mean value of serum thyroid stimulating hormone (TSH) was 0.61 mU/l pre-operatively and remained below 1 mU/l during and after operation, but from day 10 concentration began to rise steadily. It is concluded that the vast release of Tg during thyroid resection did not contribute to the concentration of serum T4 to an extent of clinical relevance.

Adult

Thyroid stimulating antibodies in rheumatoid arthritis: an in vitro phenomenon.

The purpose of the study was to evaluate the frequency of thyroid stimulating immunoglobulins and their possible effect in vivo in patients with rheumatoid arthritis. Thyroid stimulating antibodies (TSAb) were present in 17 (68%) of 25 patients with rheumatoid arthritis, whereas only 2 (8%) had thyrotropin binding inhibiting immunoglobulins (TBII). The groups with and without TSAb were comparable with regard to sex, age, anti-inflammatory drugs, serum thyroglobulin levels, antithyroglobulin and antimicrosomal antibodies, rheumatoid factor, as well as to the serum levels of thyroxine and 3, 5, 3'-triiodothyronine. A possible stimulating effect of TSAb in vivo was evaluated by an ultrasensitive immunoradiometric assay for TSH. Both groups had normal serum TSH levels, and no significant difference was found between the two groups suggesting that the demonstration of TSAb in vitro is not always associated with a stimulation of the thyroid gland in vivo.

Adult

Short-term beta-adrenergic blockade decreases serum thyroglobulin in hyper- and euthyroid patients.

Cardioselective [Acebutolol (N = 10)] or noncardioselective [Oxprenolol (N = 9)] or [Pindolol (N = 9)] beta-adrenergic blockers were given to patients with suspected hyperthyroidism. Four h after start of the beta blockade median serum thyroglobulin (Tg) had decreased to 33 (range: 13-325) micrograms/l from 41 (range: 12-333) micrograms/l before start in the acebutolol treated group (p less than 0.05). A significant decrease in serum Tg was also found in the oxprenolol-treated group [before start: 45 (24-423) micrograms/l and after 4h: 43 (18-363) micrograms/l (p less than 0.01)] and in the pindolol-treated group [before start: 154 (33-210) micrograms/l and after 4 h: 63 (19-157) micrograms/l (p less than 0.05) treated groups. After 7 days treatment the decrease in serum Tg was significant [to 85 (34-182) micrograms/l (p less than 0.02)] only in the Pindolol-treated group. It is suggested that both hemodynamic changes as well as interference with the intrathyroidal 12 S Tg to 19 S Tg dimerization might explain the changes in serum Tg during beta blockade. Knowledge of drug influence on serum thyroglobulin is important for the interpretation of variations found in patients where thyroglobulin is being used for diagnostic purposes.

Acebutolol

Humoral autoimmune manifestation in subacute thyroiditis.

To study the autoimmune manifestations in subacute thyroiditis (SAT), the patterns of thyroid antibodies, thyroglobulin and circulating immune complexes were investigated in 10 patients during the course of the disease. Eight patients were thyrotoxic at diagnosis, and became euthyroid during recovery with a median observation of 8 months (4-30 months). Thyroid stimulating immunoglobulins were measured as TSH binding inhibiting immunoglobulins (TBII) and as thyroid stimulating antibodies (TSAb). TBII were present in all patients at least once during the observation period and remained detectable in six patients after recovery. TSAb were detected in three patients without relation to the hyperthyroid state. Thyroglobulin antibodies (TgAb) were present in four patients and persisted in three, while microsomal antibodies (MAb) were negative. Thyroglobulin (Tg) in the TgAb negative patients (n = 6) was high at diagnosis (median 229 micrograms/l, range 55-375) and fell rapidly during the course of SAT. Circulating immune complexes (CIC), which were found in all patients, reached maximal levels shortly after the onset of the disease and persisted after recovery. No correlation could be demonstrated between the different thyroid antibodies, and there was no clear relation between the levels of CIC and presence of the autoantibodies. However, the changes in CIC paralleled the changes in TBII, and it is suggested that immune complex formation is a major feature of the regulatory mechanisms controlling the immune responses in SAT.

Adult

Variations in plasma protein concentrations in individuals with ulcerative colitis: analytical and biological factors.

Eight plasma proteins were determined in specimens taken every second day during a 14 day period from eleven patients with acute ulcerative colitis. The intra-individual variations in the concentrations of albumin, orosomucoid, haptoglobin, IgG, IgA, IgM and complement factors C3 and C4 were larger than expected in normal persons. A two-way analysis of variance was applied to the normalized protein values to estimate to what extent the observed variations could be explained by analytical errors and the influence of biological factors general to all proteins, such as changes in plasma volume and distribution between plasma and extravascular space. In half the non-operated patients the changes in all proteins could be explained by the above mentioned variations. The individual variations seen in the concentrations of haptoglobin, C4 and IgM occurred at random compared to the clinical state of the disease. Only the operated patients showed a more systematic sequence of protein changes.

Analysis of Variance

Effect of clomifene on thyroid function in normal men.

To study the effect on thyroid function 100 mg of clomifene citrate was given once a day to two groups of healthy male volunteers for 5 and 12 consecutive days, respectively. In both groups serum concentrations of TSH, thyroxine, triiodothyronine, T3 resin uptake test and thyroid hormone binding proteins were measured before, during and after oral administration of clomifene. The effect of clomifene treatment was evaluated in Group 1 by means of serum FSH and LH measurements. Further in Group 2 the serum TSH response to iv TRH (200 microgram) was also investigated. The mean per cent elevations in serum concentrations of FSH and LH were 145 and 200, respectively. In Group 1 a small but statistically significant decrease within reference limits in triiodothyronine (P less than 0.01) and free thyroxine index (P less than 0.02) was found on day 4 of clomifene. On day 5 a slight increase in TSH was observed (P less than 0.05). In Group 2 the response of TSH to TRH showed a non-significant increase after 5 days and a significant increase (P less than 0.01) after 12 days of clomifene. Eight days after discontinuation of the drug the response was restored to normal. No changes in the thyroid hormone binding proteins in serum could be demonstrated. Though the observed changes were slight, they indicate that clomifene exerts an influence directly on the thyroid function.

Adult

Sex and age correlated reference values of serum thyroglobulin measured by a modified radioimmunoassay.

The aim of the present investigation was to describe variations in serum thyroglobulin in relation to sex and age in a group of normal persons. The method used was a modified double antibody radioimmunoassay characterized by pre-incubation at 37 degrees C of standard or sample with antiserum, resulting in a reduced total incubation time. Both sensitivity and precision were comparable to other published methods. Of the 152 blood-donors initially investigated, 7 were excluded due to the presence of antithyroglobulin antibodies as evidenced by a radioassay. Both sexes were equally represented with an even distribution of ages from 20-65 years. Increased serum thyroglobulin with increasing age was demonstrated, the correlation being significant in women (Kendall's tau, P less than 0.001). Detectable concentrations of serum thyroglobulin (above 1.7 microgram/1) were found in 94%. Based on the logarithmic transformation, the upper reference limits were determined for men less than or equal to 40 years: 36 microgram/l, greater than 40 years: 44 microgram/l (difference between groups not significant, P greater than 0.05), and for women less than or equal to 40 years: 30 microgram/l, greater than 40 years: 60 microgram/l (significant difference, P less than 0.005).

Adult

Serum thyroglobulin in patients with toxic and non-toxic goitres compared to sex- and age-matched control subjects.

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.

Adenoma

Anticomplementary activity in diffuse and nodular goiters.

The occurrence of anticomplementary activity and its correlation to serum thyroglobulin was investigated in 71 patients with thyroid diseases and 63 age and sex matched control subjects. The patients which were subgrouped according to thyroid function and characteristics of the goiter, were examined at the time of diagnosis. The anticomplementary activity was measured by a complement consumption (CC) assay. Sera from patients with Graves' disease and nontoxic diffuse goiter, showed stronger activity than sera from patients with nontoxic goiter. Seventeen of the patients and one of the controls were positive in the CC-assay. The percentage hemoglobin release in this assay was normally distributed using control sera but not for the patient group. There was no correlation either between CC-activity and serum concentrations of thyroglobulin or CC-activity and antibodies to the O-antigen of Yersinia enterocolitica serotype 3, thyroid cytoplasma, thyroglobulin, nuclear factors, streptolysin O, streptococ hyaluronidase, and parietal cells, respectively. However, correlation between the levels of thyroid stimulating immunoglobulins and CC-activity, was noted (Rho = 0.511, P less than 0.05), which suggests that these immunoglobulins also are present as immune complexes. Thyroglobulin--antithyroglobulin complexes preformed in vitro at high thyroglobulin concentration, gave negative results in the CC-assay.

Adult

Purification of human thyroglobulin for radioimmunoassay and testing by ultracentrifugal analysis and immunoelectrophoresis.

The development of sensitive radioimmunoassays for the measurement of thyroglobulin (Tg) in human serum has demanded a high degree of purity of the Tg preparation. A procedure for purification of Tg including immunological methods for both purification and control of purity was therefore used. Extract of human thyroid glandular tissue from a patient with Grave's disease was chromatographed on Sepharose CL6B and subsequently on an affinity column containing antibody to whole human serum. Control of both purification steps was by fused rocket electrophoresis of fractions and crossed immunoelectrophoresis of the concentrated solutions. It could thus be shown that traces of contaminating serum proteins, present after column chromatography, were removed by affinity chromatography. Ultracentrifugation of 125I-labelled Tg indicated that it had a sedimentation rate corresponding to 19 S.

Humans

Thyroglobulin of varying molecular sizes with different disappearance rates in plasma following subtotal thyroidectomy.

To investigate the possible presence of thyroglobulin (Tg of different molecular sizes in plasma, blood specimens were drawn from patients during and after surgery for thyroid adenoma. Tg was measured in all serum samples by a radioimmunoassay. Selected samples were fractionated on a sepharose CL-6B column, and the fractions were assayed for Tg antigen. In serum drawn at maximum Tg concentration, molecular weights of Tg antigen ranging from 660,000 (19S) to less than 100,000 were found. 6 h later the Tg antigen of mol. wt. less than 100,000 could not be detected, and after 3 days only 19S Tg was present. Correspondingly the plasma Tg concentration vs. time curve showed a biphasic course from which two half-lives could be estimated. For 19S Tg, ta1/2 had a mean value of 4.3 days, whereas the over-all half-life for the mixture of smaller molecules, tb1/2, had a mean value of 3.7 h. The smaller molecules also showed different antigenic reactivity in the assay indicating an altered structure of the molecules. The assumption that this might be due to lack of sialic acid would explain the faster catabolic rate.

Antigens