Showing papers on "Thyroglobulin published in 1980"

Culture of hormone-dependent functional epithelial cells from rat thyroids

Abstract: Primary cultures of rat thyroid cells were made in medium supplemented with 0.1--0.5% calf serum and containing six hormones or growth factors: insulin, thyrotropin, transferrin, hydrocortisone, somatostatin, and glycyl-L-histidyl-L-lysine acetate. The FRTL strain was purified by successive colonial isolations and was found to maintain highly differentiated features (secretion into the culture medium of physiological amounts of thyroglobulin and concentration of iodide by 100-fold). The FRTL strain has been observed for more than 3 years in continuous culture. It has maintained the same biochemical and morphological characteristics that typified the primary cultures of thyroid follicular cells immediately after their enzymatic release from the rat thyroid. Thyroid epithelial cells that were grown under more conventional cell culture conditions failed to retain these specialized characteristics. We show that maintenance in vitro of these specialized functions of rat thyroid follicular cells is dependent on low serum concentrations and supplementation with hormones in the primary cultures. Our observations indicate that this culture strategem may be aplicable to the general problem of maintenance of differentiated characteristics in cultures of other epithelial cells.

Circulating Thyroglobulin and Thyroid Hormones in Patients with Metastases of Differentiated Thyroid Carcinoma: Relationship to Serum Thyrotropin Levels

Abstract: Twenty-six patients with metastases of differentiated thyroid carcinoma werestudied after total thyroid ablation. After T3 withdrawal, serum TSH, T4) and T3 were measured in all patients, thyroglobulin (Tg) was determinedin 11 patients, and rT3 was measured in 16 patients. Group 1 included 19 patients with radioiodine uptake in their metastases. The time course of change in serum TSHdiffered from patient to patient, ranging on the 10th day from 14–245 µU/ml and reaching a maximal value of 22–360 µU/ml. Tg levels increased in the 8 patients of this group who were studied and reached a plateau ranging from2.3–20 times its initial value. This increase was significantly correlated withtheserum TSH plateau level (r = 0.88; P < 0.01). T3 became detectable in only 3 cases, and T4 was detectable in only one of these 3 cases; rT3 reached the limit of detectability only in this case. Group 2 included seven patients without radioiodine uptake in the metastases. The timecourse of change in serum TSH levels and maxima...

Serum thyroglobulin concentrations and 131I whole body scans in the diagnosis of metastases from differentiated thyroid carcinoma (after thyroidectomy).

Abstract: SUMMARY. Measurements of circulating thyroglobulin (hTg) and 131I whole body scan were performed in 101 patients with differentiated thyroid carcinoma who had been subjected to surgical thyroidectomy and 131I ablation of remaining thyroid tissue. All 45 patients with positive scans (i.e. functioning metastases) had elevated hTg concentrations. Of fifty-six patients with negative scans forty-two had undetectable or very low hTg levels and were considered to be free of metastatic thyroid tissue, whereas fourteen showed the presence of non-functioning metastases in the clinical and/or radiological examination. In this group of patients, eleven had elevated serum hTg levels while the other three patients had detectable hTg concentrations within the normal range. These results indicate that serum hTg measurements correlate very well with scan findings and have the added advantage of detecting non-functioning metastases which would not be detected by scanning. We concluded that measurement of serum hTg may be used together with scanning, as the first step in the follow-up of thyroidectomized patients with differentiated thyroid carcinoma.

Restrictions in the response to autologous thyroglobulin in the human.

Abstract: Fragments of thyroglobulin containing the autoreactive epitopes were prepared by an existing procedure, plus an ion-exchange chromatography step which increased their purity. Before purification, 39% of the fragmental material was bound by rabbit anti-human thyroglobulin whereas only 8% was bound by autoantibody, thus confirming earlier reports of more limited epitopes for human autoantibodies than heterologous antibody. Thyroglobulin autoantibodies in the globulin fractions from six human sera showed between 70 and 100% cross-reaction with one another, indicating that the majority of antibodies are directed against the same epitopes. The data are consistent with an estimated of two distinct major epitopic specificities with occasional sera having antibodies directed against a third site. Chemical modification of tyrosine residues by iodination did not inhibit the binding of thyroglobulin to either human autoantibodies or rabbit anti-human thyroglobulin; thus tyrosine residues do not contribute significantly to the epitopes for either auto- or heteroantibodies.

Long-term variability in serum thyroglobulin and thyroid related hormones in healthy subjects

Abstract: From 5 young males and 5 young females blood was drawn under highly standardized conditions at 6 to 10 occasions during 4 months. The serum constituents thyroglobulin, thyroxine, triiodothyronine, T3-uptake test, TBG and TSH were determined, and four indices were calculated. The biological intra-individual coefficients of variation were below 0.14 for thyroglobulin, and the inter-individual coefficients for variation ranged from zero for T3-uptake test to 0.35 for thyroglobulin. All results were within the generally accepted reference ranges for normals. Within these ranges the calculations of indices for free thyroxine and triidothyronine according to T3-uptake test and TBG, did not significantly reduce the coefficients of variation for these serum constituents. Thyroglobulin concentrations did not correlate to any of the measured or calculated constituents. The knowledge of these intra- and inter-individual variations of serum thyroglobulin in healthy persons is of importance for the interpretation of variations found in patients.

Characteristics of 108 thyroid cancers detected by screening in a population with a history of head and neck irradiation

Abstract: One hundred and eight cases of thyroid cancer have been discovered as a result of screening 1712 individuals from a well defined population known to be at high risk because of prior head or neck irradiation for benign conditions. Of these 198 cancers, 43 (39.8%) were palpable, 27 (25.0%) were detectable by means of thyroid scintigraphy alone, and 38 (35.2%), referred to as incidental carcinomas, were found when the patients were operated on for lesions which approved to be benign. The most striking feature of these cancers was the high frequency of multicentricity (55%) and bilaterality (36%). This high frequency was found in clinically apparent as well as incidental cancers, and could not be accounted for by the operative pathologic techniques of investigation. Of 42 subjects reevaluated at our institution after a mean time of 38 months, 2 had definite and 2 had probable recurrent or residual thyroid disease. The postoperative thyroglobulin levels in subjects with thyroid cancer were proportional to the amount of thyroid tissue remaining. Follow-up evaluation of the entire group did not disclose any differences in the behavior of these thyroid cancers compared to those not associated with radiation.

Development and cytodifferentiation of C cell complexes in dog fetal thyroids. An immunohistochemical study using anti-calcitonin, anti-C-thyroglobulin and anti-19S thyroglobulin antisera.

Abstract: The development of C-cell complexes was investigated in dog fetuses by an immunoperoxidase method with three specific antisera: anti-calcitonin, anti-C-thyroglobulin (C-Tg), and anti-19S thyroglobulin. Ultimobranchial bodies joined with the thyroid anlage and then dispersed into the parenchyma to form large C cell groups. Sparse reaction products of C-Tg initially appeared in C cells with small amounts of cytoplasm. Later at about day 39 of gestation, when the immunoreactivity of calcitonin and 19S thyroglobulin appeared weakly in C cells and follicular cells, C-cell complexes were identified as large cell masses containing numerous undifferentiated cells without no immunoreactivity for any of the antisera. As development proceeded, the undifferentiated cells developed progressively the morphology of C cells. In addition, the undifferentiated cells developed 19S thyroglobulin immunoreactivity, that is, within some of the complexes small clusters of cells filled with material immunoreactive for 19S thyroglobulin. They were not organized into follicles during the fetal period, and were very slow in development. Depending on the degree of development of the undifferentiated cells, several features of the complexes were noted. The present study indicates that not only C cells but also follicular thyroid cells appear to be derived from the ultimobranchial bodies.

An enzyme-linked immunosorbent assay (ELISA) for antibodies to thyroglobulin.

Abstract: SummaryAn enzyme-linked immunosorbent assay (ELISA) was developed for the detection of thyroglobulin antibodies. The ELISA was compared with an indirect hemagglutination technique using thyroglobulin coupled to human group O erythrocytes with chromic chloride. The overall correlation between the two techniques was 0.82 (P < 0.001). ELISA proved to be suitable for large-scale screening, as all reagents are stable, with a long shelf life. However, because of its lower sensitivity, it will probably not as yet replace the chromic chloride IHA test.

Immunohistochemical analysis of thyroglobulin synthesis in thyroid carcinomas

Abstract: This immuno-histochemical description of thyroglobulin synthesis in human thyroid carcinomas is based on the analysis of 72 malignant thyroid neoplasms and about 100 cases of thyroid adenomas and other diseases of the thyroid gland. In our experience immuno-histochemistry has been an invaluable diagnostic adjunct to light microscopy for three reasons: 1) as an approach to a functional classification of thyroid carcinomas, 2) as an aid in the differential diagnosis of thyroid carcinomas of follicle cell type from tumors of other origins, 3) as an aid in the functional classification of non-cancerous thyroid tissue. In the field of metastasizing thyroid carcinoma this immuno-histochemical approach combined with a morphometrical method may enable accurate identification of patients for whom radioiodine therapy is appropriate.

Congenital Hypothyroidism Associated with Thyrotropin Unresponsiveness and Thyroid Cell Membrane Alterations

Abstract: TSH stimulates thyroid functions via the TSH receptor-adenylate cyclase (AC) system. Congenital alterations of this system might be expected to result in thyroid dysfunction. This report concerns a 17-yr-old boy in whom congenital hypothyroidism was noted at the age of 18 months. The thyroid gland was not enlarged and was in a normal position, as confirmed by scintiscan. Treatment with dessicated thyroid allowed satisfactory development. The following investigations were performed 1 month after the treatment was stopped. Serum levels were: T3≤5 ng/dl; T4 ≤1 μg/dl;thyroglobulin,≤l ng/ml; and TSH, 385 μU/ml by RIA and 400 μU/ml by the McKenzie bioassay. 131I thyroidal uptake studies showed that the increase over the basal uptake was higher after dibutyryl cAMP administration (0.1 mg/kg-min for 1 h) than after TSH stimulation, which gave essentially noresponse. Light microscopy of a biopsy specimen of the isthmus obtained under local anesthesia showed a heterogeneous cellular activity; the follicles were of ...

Iodine induced thyrotoxicosis in apparently normal thyroid glands

Abstract: Two male patients aged 36 and 52 years with thyrotoxicosis revealed a serum T3 of 28 and 65 nmol/l and a serum T4 of 166 and 238 nmol/l, respectively Both had been exposed to iodine (2-10 mg daily) for 2-12 months before thyrotoxicosis was diagnosed Urinary iodine excretion was high, 5000 and 10,000 nmol/24 h (624-1250 microgram) The uptake of 131I in the thyroid glands were low, none had goitre Their iodine intake was interrupted, urinary iodine excretion gradually decreased, and T3 and T4 in serum concomitantly normalized They were clinically and biochemically euthyroid 9 and 11 weeks after withdrawal After 14 and 22 weeks they had normal thyroid uptake of 131I, and thyroid scans showed glands of normal size and configuration TRH-stimulation and a T3-suppression tests became normal ESR was not elevated in any of the cases, thyroid antibodies against thyroglobulin and follicular cell microsomes were absent and TSAb was undetectable durng the thyrotoxic stage Thus no evidence of any pre-existing and/or pre-disposing pathological condition in the thyroid glands were found The mechanism for the iodine-induced thyrotoxicosis in such cases remains obscure

Effects of organic and inorganic mercurials on thyroidal functions

Abstract: Acute effects of methylmcrcuric chloride and mercuric chloride on thyroidal functions were examined. The organic mercurial concentration of 4×10-5 M inhibited by 50% of Na+K+ ATPase in the membraneous preparation from the hog thyroid, and 6×10-7 M of the inorganic mercurial showed the same extent of the inhibition. The Mg2+ATPase activity in the preparation was neither affected by CH3HgCl up to a concentration of 2×10-3 M, nor by HgCl2 up to 1×10-4 M. After an intraperitoneal injection to mice of 5 μg of mercurial per gram body weight daily for 2 consecutive days, the 4-hour and the 24-hour uptakes of 131I by the thyroids were partially reduced by both organic and inorganic mercurials. A significant reduction in percentages of labeled iodothyronines was demonstrated to suggest that mercurial may cause a coupling defect in the synthesis of iodothyronines. Incubation of hog thyroglobulin with 8×10-3 M of methylmercuric chloride caused no observable aberration in slab disc electrophoreogram, but the protein was apparently denatured by the same concentration of mercuric chloride suggesting that thyroglobulin may carry a large binding capacity against either mercurial, but the inorganic mercurial can be more potent denaturant of the protein. The in vitro lysosomal hydrolysis of the mercurialpretreated rat thyroglobulin which was labeled with 125I in vivo and fortified with the carrier hog thyroglobulin was not affected, but the direct addition of either mercurial in the medium resulted in a significant inhibition of the proteolytic action. Iodotyrosine deiodinase in the thyroid was inhibited by both mercurials in in vitro and in vivo systems. A partial reduction in the serum bound 131I-iodide in both mercurial treated groups was observed at 4 hours and 24 hours after the radioiodide administration. The blood thyroxine levels estimated by radioimmunoassay were quite reduced in the inorganic mercurial treated group and also moderately reduced in the methylmercurial treated group, indicating that the hormone secretion was affected by mercurials.

An improved co-precipitation assay for determination of thyroglobulin antibodies.

Abstract: A radioassay for determination of thyroglobulin antibodies in human serum using [125I]thyroglobulin co-precipitated with antihuman IgG is described. Serial dilutions of the antibody containing sera gave nearly rectilinear and parallel logit-log curves in conditions of moderate antigen excess. A secondary standard serum calibrated against the Medical Research Council Research standard A 65/93, which by definition contains 1 Mega unit/1 (MU/1) was used for standardization. The mean imprecision in the concentration range 0.74-241 MU/1 was CV = 3% (within assay) and CV = 8% (total). The detection limit was 0.002 MU/1. The assay was compared to an antigen binding capacity method with an imprecision of 15% (total) and a detection limit of 0.1 MU/1. The coefficient of correlation between the two methods was: R = 0.997 (our method = 0.019 × antigen binding capacity-0.33) Based on this 1 Mega unit was found equivalent to 53 nmol thyroglobulin.

Biochemical and immunological investigations on hypothyroidism in dogs.

Abstract: Circulating antibody titers (1:20 to 1:2560) against thyroglobulin were demonstrated in 48% of pet dogs with hypothyroidism by the chromic chloride passive hemagglutination test. Four of six dogs with acanthosis nigricans (1:20) and one of six male dogs with hyperestrogenism (1:40) had low titers of antibody against thyroglobulin whereas clinically normal pet dogs and dogs with other selected endocrinopathies (hypoadrenocorticism, cortisol-excess, diabetes mellitus) or obesity were consistently negative. Circulating immune complexes evaluated by the mastocytoma cell-assay were present in the sera of 20% of pet dogs with hypothyroidism but were absent in clinically normal dogs. Although variations in dose significantly altered the quantitative response of the thyroid gland to thyrotropin the qualitative pattern of response was similar for T3 but not T4 in clinically normal laboratory beagles. The peak increases for serum triiodothyronine and thyroxine were observed either at eight (0.1 and 0.2 I.U bTSH/5 lbs) or 12 (1.0 I.U. bTYSH/5 lbs) hours postthyrotropin. Dogs with naturally occurring hypothyroidism had a decreased serum T3 and T4 at baseline and eight hours postthyrotropin (1.0 I.U. bTSH/5 lbs) compared to clinically normal pet dogs, laboratory beagles and dogs with other clinical endocrinopathies. The consistent lack of a significant increase of serum T3 and T4 in response to thyrotropin was necessary for the separation of certain hypothyroid from euthyroid pet dogs in which the baseline level of thyroid hormones were equivocal.

Follow-up of patients with differentiated thyroid cancer using serum thyroglobulin measured by an immunoradiometric assay. Comparison with I-131 total body scans.

Abstract: An immunoradiometric assay for thyroglobulin (Tg), which allows quantification of Tg in the presence of anti- Tg, has been evaluated in patients with differentiated thyroid cancer. All patients had undergone thyroidectomy plus I- 131 ablation. Three separate studies have been conducted. 1. Tg levels were compared with I- 131 whole-body scans made at 48 hr in 22 patient studies. Both tests gave similar results in 19 of the studies, but in three patients the results of the tests were discordant. 2. Tg levels were compared with clinical status in 18 patients who were free of disease; 15 had Tg values < 5 ng/ml, and three had measurable but normal Tg values. Three patients with metastatic disease had measurable Tg, and in two the values were above normal. 3. Sequential Tg measurements were made at intervals of 3 mo in 19 patients on thyroxine. Fifteen of these patients had identical results on two or more occasions.

SEQUENTIAL CHANGES IN SERUM THYROGLOBULIN (Tg) AND ITS AUTOANTIBODIES (TgAb) FOLLOWING SUBTOTAL THYROIDECTOMY OF PATIENTS WITH PREOPERATIVELY DETECTABLE TgAb

Abstract: SUMMARY The changes in serum concentrations of thyroglobulin antibodies (TgAb) were investigated in eight patients with various thyroid disorders before, during and after thyroid surgery. TgAb was measured by a radioassay using 125I-thyroglobulin. In six patients the TgAb decreased rapidly during operation. Of these patients, four had low concentrations pre-operatively, and the decrease in TgAb resulted in undetectable concentrations for more than 2 days. Serum thyroglobulin (Tg), measured in the specimens with undetectable TgAb, i.e. immediately following surgery, showed concentration vs time curves resembling curves from patients with no antibody present. Furthermore, two of these patients had such a high concentration of TgAb pre-operatively that the initial Tg release was not sufficient to remove the TgAb, resulting in detectable TgAb throughout the investigation period. Serum samples drawn during and after operation were chromatographed according to molecular size, showing measureable Tg corresponding to 19S Tg. TgAb was only measureable in fractions corresponding to 7S IgG. The expected presence of complexed Tg and TgAb could not be demonstrated, but the analytical methods might have been unable to reveal this. The remaining two patients with thyroiditis showed no decrease in TgAb. This was compatible with a low content of Tg in the thyroid measured in one of them.

Hla antigens and thyroid autoantibodies in patients with graves' disease and their first degree relatives

Abstract: SUMMARY Patients with Graves' disease (n= 105) had an increased frequency of HLA-B8 (40%) and a reduced frequency of HLA-B12 (24·8%) when compared with random controls (n=117; 24·8% and 40·2% respectively). Comparison of patients with their first degree relatives (n= 118) shows the frequency deviations in these antigens to be characteristic of the families from which patients with Graves' disease are drawn, rather than of the disease itself. The haplotypes, identified in eighty-six patients and 113 relatives, indicate that the excess of HLA-B8 in patients and their relatives is primarily due to the haplotype 1–8. The relative risk for an HLA-B8 individual of developing Graves' disease is 2·02, whilst the relative risk for an individual of haplotype 1–8 is 4·23. No significant associations were found between the incidence of any HLA antigen or combination thereof and the presence or absence of thyroglobulin and thyroid microsomal antibodies, or antibodies which interact with the TSH receptor.

H‐2 gene products influence susceptibility of target thyroid gland to damage in experimental autoimmune thyroiditis

Abstract: The restriction of the pathogenesis of experimental autoimmune thyroiditis (EAT) by H-2 gene products was investigated. EAT was induced by injecting thyroglobulin extract plus adjuvant into F1, hybrid mice that had been implanted under the kidney capsules with thyroid glands originating from either the EAT-susceptible or -resistant parental strain mice. We found relative H-2 restriction of thyroid damage to those glands originating from the H-2-susceptible parental strain. H-2 restriction of damage at the level of the target thyroid gland implicates cytotoxic effector T lymphocytes as a pathogenic agent of EAT.

Clearance of normal and tumor-related thyroglobulin from the circulation of rats: Role of the terminal sialic acid residues

Abstract: The transplantable rat thyroid tumor 1-1C2 has been used to study circulating thyroglobulin (TG) related to thyroid cancer. Since tumor 1-1C2 is defective in its ability to incorporate sialic acid into TG, the role of the terminal carbohydrate residues in the clearance of rat TG from the circulation was also studied. Sialic acid was removed from normal TG by treatment with V. cholerae neuraminidase (asialo-TG) and the newly exposed galactose residues were oxidized with galactose oxidase (galox-TG). Native TG, the modified TGs, and tumor TG gave parallel radioimmunoassay displacement curves. These preparations were injected into rats that had been thyroidectomized by surgery and 131 I − and subsequently maintained on T 3 . The clearance rates were determined by measuring sequential plasma concentrations by radioimmunoassay. The circulating TG in tumor-bearing rats had sedimentation properties characteristic of poorly iodinated TG. At low temperature the sedimentation rate decreased and there was partial dissociation into subunits. The half-life of native TG was 4.4 hr whereas asialo-TG disappeared from the rat circulation 18-fold faster, with a half-life of 15 min. The half-life of TG isolated from the 1-1C2 tumor, 12 min, was also much more rapid than native TG half-life. Compared with asialo-TG and tumor TG, the half-life of galox-TG, 1.5 hr, returned towards normal. Asialofetuin competed with asialo-TG for degradation and prolonged the circulating lifetime of the latter. These results suggest that TG is cleared from the circulation by the same pathway used for fetuin and therefore by the common degradative pathway for glycoproteins. Sialic acid residues protect circulating TG by shielding its galactose residues, which are recognized by the degradative system. The TG of the 1-1C2 tumor behaves like poorly iodinated, sialic-acid-poor TG. The 1-1C2 transplantable tumor should be a useful model for the study of circulating TG related to thyroid cancer.

Thyroid abnormalities in children of parents who have Graves' disease: possible pre-Graves' disease.

Abstract: We have studied possible premonitory features of Graves' disease among offspring of parents who had this condition. One-hundred-fifty-three children of parents with Graves' disease were examined, as were 129 control children selected on the basis of a negative history for Graves' disease among first-degree relatives. Examination consisted of a physical examination, brief medical history, and determination of a variety of thyroid function and autoimmunity tests. Thirty-six percent of children of parents with Graves' disease had one or more abnormality, as compared to 24% of the control children. The incidence of abnormalities increased with age and were more common in females. The abnormalities in both groups were similar in variety and intensity, and differed mainly quantitatively in frequency. Half of the minor abnormalities detected in the thyroid, including firmness, enlargement, or lobulations, were accompanied by chemical abnormalities such as a high or low T4 level, abnormal thyroglobulin or triiodothyronine (T3) level, or the presence of antithyroid antibodies. One quarter of children having some minor abnormality in the thyroid had definite evidence of Hashimoto's thyroiditis. Bioassays for long-acting thyroid stimulator (LATS) were positive in 2 of 95 children of parents with Graves' disease, and in 1 of 49 control children. Assays for thyroid stimulatory immunoglobulins, cell-mediated immunity to thyroid antigens, and thyroglobulin immune complexes were negative. There was a clustering of abnormalities in certain families, suggesting that these families may be prone to develop subsequent clinical illness. During follow-up examination extending over 3 yr, a significant fraction of children lost or modified the original abnormality or developed a new abnormality. During observation, one child developed asymptomatic thyrotoxicosis, one developed exophthalmos, one developed vitiligo, and one had the onset of Hashimoto's thyroiditis. The data suggest that there is a progressive evolution of abnormalities in thyroid function, and that these are especially common within certain families. It may be possible to determine from sequential examinations which children are at risk, with a high degree of probability of developing thyrotoxicosis. The abnormalities found in these children change from year to year and do not represent a necessarily progressive process. The data indicate the presence of a condition that may be called “Pre-Graves' Disease”, a dynamic state of disordered antithyroid immunity, which may lead to overt thyrotoxicosis in some children.

H-2K mutation controls immune response phenotype of autoimmune thyroiditis. Critical expression of mutant gene product in both thymus and thyroid glands.

Abstract: Autoimmune thyroiditis (EAT) can be induced by immunizing mice against mouse thyroglobulin. A gene critical to the phenotypical expression of EAT was mapped to the H-2K locus by studying B6 mice and its mutant strain B6.H-2ba. To identify organs in which expression of the gene was decisive for the EAT phenotype, we transplanted thyroid or irradiated thymus glands into various strains of normal mice or thymusless nude mice. We found that the pathophysiology of EAT was controlled by the expression of specific H-2 genes in both the target thyroid gland and the thymus gland.