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Biomedical subjects

U Feldt-Rasmussen

Publications and source records attributed to U Feldt-Rasmussen.

At least 37 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 Fourteen patients had been treated with L-thyroxine, which was withdrawn during the investigation.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

Thyroid function in patients with breast cancer.

Thyroid function was evaluated in 58 patients with breast cancer and compared with data obtained from an age-matched control group of healthy women. Thyroid antibodies at low levels were present in 29 patients (50%): 21 patients (36%) had thyroid stimulating antibodies at low activity. Ten patients (17%) had thyroglobulin antibodies compared with 3 in the control group (P less than 0.05). Nine of 10 patients with thyroglobulin antibodies had microsomal antibodies as well. Two patients had only microsomal antibodies. Additionally 10 autoimmune antibodies were determined. These were, however, either absent or present in low concentrations in serum. Independent of the stage of disease, no differences were demonstrated between patients and controls in serum levels of triiodothyronine, thyroxine, free T3 index, free T4 index, thyroid stimulating hormone, and thyroglobulin. In conclusion, we found an increased frequency of thyroid autoantibodies in euthyroid patients with breast cancer compared with healthy controls suggesting a possible relation between this disease and autoimmune thyroid disease.

Adult

Serum thyroglobulin in chronic renal failure--effects of haemodialysis.

The influence of chronic renal failure (CRF) on serum thyroglobulin concentration (Tg) was investigated in 37 patients (29 on haemodialysis) and compared with results obtained from matched controls. Serum Tg did not differ significantly between CRF patients not on haemodialysis: median 24.1 micrograms/l, (range 2.5-47.0) and controls: median 23.6 micrograms/l, (range 2.1-53.0). Patients on haemodialysis had a significantly lower serum Tg level: median 11.4 micrograms/l (range 2.1-54.0) compared to controls (p less than 0.01) but no change in serum Tg level could be demonstrated after a single haemodialysis. A possible explanation for the low serum Tg level in patients with CRF on haemodialysis is decreased production parallelling the decreased production rate of T4 and T3. Since CRF patients not on haemodialysis had an unchanged serum Tg level compared to controls, haemodialysis was associated with small changes in serum Tg level, and since none of the patients had a serum Tg value above the upper reference limit we conclude that these changes were not of a magnitude likely to cause misinterpretation of results in routine clinical situations.

Adolescent

IgG subclass distribution of thyroid autoantibodies: a 'fingerprint' of an individual's response to thyroglobulin and thyroid microsomal antigen.

The IgG subclass distribution of autoantibodies to thyroglobulin and thyroid microsomal antigen was studied in 21 patients with Graves' disease during fluctuations in total IgG class autoantibody levels induced by various forms of therapy. In addition, changes in autoantibody subclass distributions were investigated during the natural course of Hashimoto's disease in seven patients taking thyroxine. The autoantibodies were principally of subclasses IgG1 and/or IgG4 in Graves' patients although IgG2 contributed significantly to thyroglobulin antibodies in 5/7 Hashimoto sera. In Graves' disease the distribution of microsomal and thyroglobulin antibodies among the IgG subclasses remained essentially unchanged over periods of 6 months-2 years whether autoantibody levels decreased during carbimazole therapy or increased transiently following 131Iodine treatment or subtotal thyroidectomy. Similar observations were made for thyroglobulin antibodies in Hashimoto patients studied over 2 1/2-4 years; furthermore, the IgG subclass distribution of microsomal antibodies was usually different from that of thyroglobulin antibodies in the same patient. These observations suggest that the microsomal and/or thyroglobulin antibody subclass distribution is characteristic for a particular individual and may be regarded as the 'fingerprint' of an individual's response to these thyroid autoantigens.

Adolescent

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism.

Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied in the euthyroid state. Mean arterial pressure was reduced in mean by 20 mmHg (+/- 6 mmHg, P less than 0.02) during treatment and a significant vasoconstriction was observed both during arm lowering (SBF = -52% (+/- 6%, P less than 0.02)) and in head-up vertical position (SBF = -45% (+/- 11%, P less than 0.02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment.

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

Autoreactive lymphocytes in thyroid disorders. Quantitation of anti-thyroglobulin antibody formation by a specific haemolytic plaque forming cell (PFC) assay.

Blood mononuclear cells (MNC) from 21 patients with autoimmune thyroiditis were assayed for secretion of immunoglobulins in vitro by a reverse haemolytic plaque forming cell (PFC) assay. An antigen-specific assay was employed to quantify anti-thyroglobulin antibody (TgAb) secreting cells. The sensitivities of the two PFC assays were similar. The antigen specificity of the Tg-PFC assay was demonstrated by the ability of free Tg to inhibit PFC formation. The number of spontaneous TgAb-secreting cells was low (median 3 IgG-Tg-PFC/10(6), range 0-35/10(6)); TgAb activity was found in 3% (range 0-11%) of total IgG-PFC. The number of spontaneous IgG-TgAb-secreting cells correlated positively to TgAb titres in serum. MNC from most patients secreted IgG-TgAb upon polyclonal stimulation in vitro for six days with pokeweed mitogen (52 IgG-Tg-PFC/10(6), range 0-478/10(6)); TgAb activity was found among 2% (range 0-8%) of total IgG-PFC. Again, pokeweed mitogen-induced TgAb secretion correlated positively to TgAb titres in serum. Finally, MNC from most patients secreted TgAb after culture with Tg. The Tg-induced response was about 1/3 of the pokeweed mitogen-induced TgAb response. Tg did not increase the production of total IgG indicating that Tg is not a polyclonal stimulus. Few TgAb-secreting MNC were discovered in euthyroid sex and age-matched control patients.

Aged

Autoreactive lymphocytes in thyroid disorders. II. Comparison of anti-thyroglobulin antibody production by plaque-forming cell, radio-immunological and enzyme-linked immunosorbent assays.

Blood mononuclear cells (MNC) from 9 randomly selected patients with autoimmune thyroiditis were stimulated in vitro with pokeweed mitogen (PWM), a polyclonal B lymphocyte activator. The secretion of immunoglobulins (Ig) and anti-thyroglobulin antibodies (TgAb) was assayed by means of haemolytic plaque-forming cell (PFC) assays, radio-immune assay (RIA) and enzyme-linked immunosorbent assays (ELISA). Total Ig and TgAb production was maximal using MNC cultured at 1.0 X 10(6)/ml as estimated by PFC, RIA and ELISA. The Ig and TgAb production as measured by RIA and ELISA was 1.5 - 3 times higher after 12 days' culture compared to 6 days' culture. Ig and TgAb production measured by PFC-assays at day 6 correlated positively to the results obtained by RIA and ELISA at day 12. PWM-induced TgAb secretion correlated positively to TgAb titres in serum. As judged by PFC, TgAb production was found in 8/9 patients; about 5% (range 0 - 7.9%) of the total PWM-stimulated IgG-secreting cells were involved in TgAb secretion. TgAb production as measured by ELISA and RIA was found in 6/9 patients. By reference to an affinity-purified human TgAb preparation, the TgAb secretion was about 0.7% (range 0 - 21.3%) of the total PWM-induced IgG secretion.

Antibody Formation

Comparison between homogeneous phase radioassay and enzyme-linked immunosorbent assay for measurement of antithyroglobulin antibody content in serum. Relation to presence of thyroglobulin.

The aim of the study was to test the influence of thyroglobulin in vitro and in vivo on two different principles for quantification of serum antithyroglobulin antibody content. The methods employed were a previously described homogeneous phase radioassay and a newly developed enzyme-linked immunosorbent assay. Thyroglobulin inhibited the measurement of antithyroglobulin antibody content by both methods, not only by addition in vitro but also when present in vivo as a result of release from thyroid surgery. Both methods proved sufficiently sensitive as screening for presence of antithyroglobulin antibodies before measurement of thyroglobulin in serum. The study shows the importance of assessing the assay systems in each laboratory for interference before use, especially if intended for screening before quantifying serum thyroglobulin or for measurement of antithyroglobulin antibodies in other media (e.g. supernatants from lymphocyte cultures).

Adult