[Thyroglobulin autoantibodies. Current methodological and prognostic aspects].
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Biomedical subjects
Publications and source records attributed to U Feldt-Rasmussen.
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Thyroid function, the clinical occurrence of goitre and ultrasonically determined thyroid gland volume were investigated in 23 patients with phenytoin- and 28 patients with carbamazepine-treated convulsive disorders and compared with matched healthy controls. In the phenytoin treated group median thyroid volume was 26 ml (range 14-57 ml) compared to 17 ml (range 8-41 ml) in the controls (P less than 0.01). Ten patients and four controls had a goitre (NS). Median serum T4 and FT4I levels were reduced, serum TSH level increased and serum T3, T3RU, FT3I and thyroglobulin levels unaltered compared with the controls. In the carbamazepine treated group median thyroid volume was 25 ml (range 13-66 ml) compared to 16 ml (range 9-44 ml) in the controls (P less than 0.01). Thirteen patients and three controls had a goitre (P less than 0.02). Median serum T4, FT4I and FT3I levels were reduced, serum thyroglobulin increased and serum T3, T3RU and TSH levels unaltered compared with the controls. The increase in thyroid size is probably a compensatory mechanism due to the low free thyroid hormones in serum caused by an increased hepatic degradation of thyroid hormones by phenytoin and carbamazepine.
Thyroid function, the clinical occurrence of goitre and ultrasonically determined thyroid gland volume were investigated in 219 healthy subjects randomly chosen from hospital employees. Thirty-five subjects (16%) had a clinically detectable goitre. The frequency of goitre among smokers was higher (32 of 107, 30%) than among non-smokers (3 of 112, 3%), (P less than 0.001). Median thyroid volume was significantly higher in smokers, 26 ml (range 11-55 ml), compared with non-smokers, 15 ml (range 8-37 ml), (P less than 0.001). The median serum thyroglobulin levels were significantly higher and median serum thyrotropin levels lower in smokers compared with non-smokers. There were no differences between the groups regarding serum levels of T4, T3, rT3, free T4 index, free T3 index, thyroglobulin antibodies and 131I uptake (24 h) in the thyroid gland. It is suggested that these findings could partly be due to inhaled thiocyanate and/or increased adrenergic stimulation of the thyroid gland in smokers.
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.
The aim of the study was to develop an enzyme linked immunosorbent assay (ELISA) for measuring thyroglobulin (Tg) in human serum and to evaluate the influence of serum thyroglobulin auto-antibodies (TgAb) on the ELISA. The sensitivity of the ELISA was 2.1 micrograms/l. Serum Tg levels in healthy controls were from less than 2.1 to 55.5 micrograms/l (n = 46) (95% reference range). With serum Tg concentrations between 19.6 to 90 micrograms/l the within-assay coefficient of variation (CV) was from 4.5 to 6.6% (n = 12) and the between-assay CV from 8.5 to 10.5% (n = 6). The recovery from 20 to 89 micrograms Tg/l serum was from 93 to 101%. There was significant correlation between serum Tg concentrations measured by the ELISA and a RIA method in healthy controls (r = 0.85, n = 46, p less than 0.001) and in patients with differentiated thyroid carcinoma (r = 0.97, n = 28, p less than 0.001). The TgAb interfered with the serum Tg determination both in the ELISA and in the RIA method. The assay is simple and easy to perform, and the equipment is inexpensive and useful for large-scale serum Tg measurements as an alternative to RIA.
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.
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.
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).
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.
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.
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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.
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.