[Measurement of anti-thyroid peroxidase antibodies as a substitute to measurements of microsomal and thyroglobulin antibodies].
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Biomedical subjects
Publications and source records attributed to J Date.
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An immediate reduction of thyroglobulin autoantibodies during subtotal thyroidectomy of thyroglobulin antibody positive patients has previously been shown to indicate an acute release of thyroglobulin into the circulation peroperatively. The aim of the present study was to investigate whether thyroid peroxidase was also released by measuring anti-thyroid peroxidase antibodies by a quantitative and antigen specific method both pre- and postoperatively in patients positive for anti-thyroid peroxidase antibodies. Twelve anti-thyroid peroxidase positive patients (11 females, 1 male) referred for surgery of toxic goitre were studied. Median age was 43 years (range 24-64) and median goitre size 86 g (25-165). All patients had been pretreated with antithyroid drugs and were euthyroid at the time of operation. Anti-thyroid peroxidase was measured before operation, 1-8 h, 10 days, 1-3 months, and 12 months postoperatively by a commercial method (DYNO-test, Henning, Berlin). The median anti-thyroid peroxidase level before operation was 1048 kU/l (range 68-10 517 kU/l) and fell during operation to 0.63 (range 0.37-1.28) (p less than 0.01) of initial concentration without further decrease during the next 1-8 h. The comparative decrease in thyroglobulin antibodies was 0.19 (0-0.88). The anti-thyroid peroxidase level was increasing after 10 days, but did not reach initial level until between 3 and 12 months after surgery. However, in 3 of 10 patients anti-thyroid peroxidase had disappeared after 12 months, all of whom had low levels before operation, whereas anti-thyroid peroxidase was 2-4 times higher than preoperatively in 3 other patients.(ABSTRACT TRUNCATED AT 250 WORDS)
A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.
Nuclear thyroxine and triiodothyronine receptor-binding in human mononuclear blood cells were examined in 14 euthyroid persons prior to and 1, 6, 24 and 53 weeks after goitre resection. One week after resection decreased serum T3 from 1.47 nmol/l to 1.14 nmol/l (P less than 0.05), FT4I from 103 a. u. to 94 a. u. and SHBG from 80 nmol/l to 69 nmol/l (P less than 0.05) followed after 6 weeks by a rise in serum TSH from 1.2 mU/l to 11.0 mU/l (P less than 0.05) suggesting an initial slight hypothyroidism. Nuclear receptor-binding of T4 and T3 increased within one week and eventually decreased to preresectional values. We conclude that the expected alteration of the metabolic state caused by resection of the gland is opposed by increased nuclear binding of T4 and T3.
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.
The excretion of urinary iodine was studied in a representative population sample from the county of Funen, Denmark, comprising 505 persons between 25-44 years of age, stratified according to geography, age, and sex. Urine samples were collected for 5 h during late afternoon and early evening. The 24-h iodine excretion was estimated on the basis of iodine and creatinine determinations using correlation equations determined in a pilot study of 50 men and women. The iodine excretion was significantly higher in men: 89 micrograms/24 h (median) than in women: 76 micrograms/24 h; the whole population: 85 micrograms/24 h. No significant differences were observed among the age groups studied. The iodine excretion was significantly higher in people living on small islands: 98 micrograms/24 h (median) compared with 84 micrograms/24 h in urban regions and 78 micrograms/24 h in rural districts. Median iodine excretion per gram of creatinine was 58.8 micrograms for the whole sample. The iodine excretion for men was 77% higher than reported in an earlier investigation performed in Funen, 1969, but still lower than internationally recommended (WHO).
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.
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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 effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells.
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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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.
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Human chorionic somatomammotropin concentration in serum (S-HCS) during the latter half of pregnancy was measured by radioimmunoassay and correlated to the placental weight, in two groups of normal, healthy, pregnant women. In one group, 228 samples from 47 women were examined, which gives a longitudinal series. In the other group, single samples from each of 346 pregnant women were examined, which gives a cross-sectional series. Both groups were randomized on the basis of a prospective selection. The mean values of S-HCS in each week of gestation were almost identical in the two groups, showing a steady increase until 37-38 weeks and a subsequent decrease. In the longitudinal series there was a positive correlation between the S-HCS and placental weight after 37 weeks' gestation, but not before that time. Before 37 weeks gestation the ratio S-HCS/placental weight was significantly higher with small placentae than with large placentae. This difference between small and large placentae disappeared after 37 weeks. These results point to the existence of some regulatory mechanism tending to keep the S-HCS concentration within certain limits, independent of placental weight. This mechanism appears to be lost after 37 weeks of gestation when the S-HCS concentration starts to correlate with placental weight.