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PubMed1983

The difference of susceptibility of target thyroid gland to autoimmune thyroiditis induced by a combination of implantation of thyroid gland and injection of lipopolysaccharide.

Autoimmune thyroiditis was induced in CBA/J mice by a newly developed method consisting of a combination of implantation of one whole syngeneic thyroid gland under the capsule of the kidney and subsequent injection of lipopolysaccharide (LPS) intravenously 6 hr after implantation. This procedure was repeated once, a week later. With this method the implanted thyroid gland, after becoming necrotic due to circulatory disturbance and regenerating, also developed definite thyroiditis, quite similar to that of the intact thyroid gland on Day 49. With respect to the H-2 haplotype of the mice, both intact and implanted thyroid glands of CBA/J (H-2k) and C3H/He (H-2k) mice showed severe thyroiditis, whereas those of BALB/c (H-2d) and C57BL/6 (H-2b) mice developed mild inflammation. With a combination of implantation of thyroid glands derived from parental good (CBA/J) or poor responder (BALB/c) mice and subsequent injection of LPS into (good X poor responder) (CBA/J X BALB/c)F1 hybrid mice, it was found that the genetic background of the target thyroid tissue itself has a strong influence on susceptibility.

Animals↗
PubMed1980

Effect of thyroid-stimulating hormone and norepinephrine on cyclic AMP levels in human normal thyroids and human thyroid tumors.

The effect of TSH (100mU/ml) and norepinephrine (100 muM) on the cyclic AMP levels was studied in 10 human normal tissues, 10 thyroid adenomas and 4 thyroid carcinomas (3 papillary and 1 follicular). Normal tissues responded to TSH with a marked elevation of the cyclic AMP level. Response patterns of 10 thyroid adenomas to TSH were variable; the patterns of 6 cases resembled those of normal tissues, 3 responded mildly, and one had no response to TSH. Thyroid carcinomas had a higher basal level of cyclic AMP than those of normal tissues, although they responded only slightly to TSH. Two among 4 thyroid carcinomas had no response to TSH. Norepinephrine stimulated the accumulation of cyclic AMP in 4 thyroid adenomas and 3 thyroid carcinomas, while it had little effect on normal tissues. Responses to norepinephrine was observed only in thyroid tumors, although they had low response to TSH. It is suggested from these results that tumor cells originating from thyroid follicular cells have a modified response to hormones due to neoplastic alterations.

Adenoma↗
PubMed1991

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism.

The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

Adult↗
PubMed1982

Thyroid hormone formation catalyzed by human thyroid peroxidase: a new and physiological measurement of thyroid peroxidase.

This report describes a method for measurement of TPO activity by the amount of thyroid hormone production. Thyroid hormone formation was accomplished by incubating purified iodine-poor Tg with human TPO for 60 min at 37 C in the presence of free DIT, KI, and an H2O2 source. Newly formed T3 and T4 were measured by radioimmunoassay of the Tg hydrolysates. With this method, TPO-catalyzed iodination of Tg and thyroid hormone formation were measured simultaneously from eight normal thyroid glands and 15 thyroid glands from MMI-treated patients with Graves' disease. Graves' disease TPO showed iodinating activity and T4 formation which was higher than that of TPO from normal thyroids, and there was a positive linear correlation between the iodinating activity and the amount of T4 formation. T3 production by highly active TPO, however, dissociates from the amount of T4 formation and the degree of Tg iodination. Thus, if the activity of TPO is to be measured by the amount of thyroid hormone production, T4 should be used rather than T3. The method of thyroid hormone formation described here provides a new and physiological measurement of TPO activity and should be useful for investigation of the role of human TPO in thyroid hormone formation.

Diiodotyrosine↗
PubMed1992

A thyroid biopsy with histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis.

We describe a 36-year-old woman with clinical, laboratory, and histologic features of both Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis. Features of the former included a hard, fixed thyroid mass and extensive involvement of perithyroidal tissues by dense fibrosis with lymphocytes, histiocytes, and plasma cells. Features supporting Hashimoto's thyroiditis included high serum titers of antimicrosomal and antithyroglobulin antibodies and the histologic findings within the thyroid gland itself: dense fibrous bands dividing the thyroid parenchyma into nodules composed of lymphoid follicles with germinal centers, plasma cells, and oxyphilic metaplasia of follicular epithelial cells. Although Riedel's thyroiditis and the fibrosing variant of Hashimoto's thyroiditis were once considered morphologic variants of the same disease, since the 1970s these diseases have been considered as distinct clinicopathologic entities. The coexistence of both diseases in a patient is rare and is probably coincidental in this instance.

Adult↗
PubMed1989

Thyroid-infiltrating lymphocytes, thyroid function, and HLA-DR in juvenile autoimmune thyroiditis.

Eighteen patients with juvenile autoimmune thyroiditis were studied. At diagnosis 8 (44%) of the patients were euthyroid and 10 hypothyroid, whereas at the end of 6 to 12 months follow-up, 12 (66%) were euthyroid and 6 hypothyroid. All the patients were HLA-typed. The frequency of HLA-DR4 was increased in the patients when compared with the normal population, 63 vs 28% (p less than 0.01). An analysis of thyroid-infiltrating mononuclear cells revealed that the majority of the thyroid-infiltrating lymphocytes were T cells. More T lymphocytes and fewer B lymphocytes and HLA class II positive lymphocytes were found among the thyroid-infiltrating mononuclear cells in euthyroid than hypothyroid patients. The numbers of thyroid-infiltrating B lymphocytes correlated with the levels of thyroid microsomal antibodies. No correlation was found between thyroid function and thyroid antibodies.

Adolescent↗
PubMed1987

Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases.

Recent evidence indicates that human thyroid peroxidase (TPO) has most of the characteristics of the thyroid microsomal antigen. The question of whether TPO accounts for part or all of the antigenic activity recognized by circulating anti-microsomal antigen autoantibody (anti-M Ab) remains to be determined. The availability of an anti-TPO monoclonal antibody and of a highly purified TPO preparation allowed the development of specific and sensitive radioassays for anti-TPO autoantibody (anti-TPO Ab). In this study we compared anti-M Ab and anti-TPO Ab levels in serum from 128 subjects, including patients with Hashimoto's thyroiditis (n = 31), idiopathic myxedema (n = 11), hyperthyroid Graves' disease (n = 45), miscellaneous nonautoimmune thyroid disorders (n = 9), and normal subjects (n = 32). Anti-M Ab and anti-TPO Ab were measured by radioimmunological methods employing two different assay designs: 1) competitive radioassay (CR), based on the inhibition of radioiodinated antibody binding to human thyroid microsomes coated on microtiter wells, using a) [125I]immunoglobulin G (IgG) containing a high anti-M Ab titer (for anti-M Ab determinations), or b) [125I]anti-TPO monoclonal antibody (for anti-TPO Ab); and 2) sandwich immunoradiometric assay (IRMA) using microtiter wells coated with thyroid microsomes (for anti-M Ab determinations) or immunoaffinity-purified TPO (for anti-TPO Ab determinations) and [125I]anti-human IgG antibody. Anti-M Ab also was measured by passive hemagglutination. Anti-M Ab titers by PH closely correlated with anti-TPO Ab levels whether assayed by IRMA (r = 0.905; P less than 0.00001) or CR (r = 0.922; P less than 0.00001). Even closer correlations were found when anti-M Ab and anti-TPO Ab both were measured by the same type of radioassay procedure (IRMA, r = 0.945 and P less than 0.00001; CR, r = 0.957 and P less than 0.00001). No differences in the correlation between anti-M Ab and anti-TPO Ab results were found when the data in patients with different autoimmune thyroid disorders were analyzed separately. Further and more direct evidence for the identity of anti-M Ab and anti-TPO Ab was provided by the ability of purified TPO to completely inhibit the binding to thyroid microsomes of radioiodinated IgG preparations containing high anti-M Ab titers. In conclusion, our results provide strong support for the concept that TPO accounts for virtually all of the antigenic determinants reacting with the autoantibodies commonly termed anti-M antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens↗
PubMed1985

Thyroid function after resection for non-toxic goitre with special reference to thyroid lymphocytic aggregation and circulating thyroid autoantibodies.

A series of 91 patients operated on for non-toxic goitre was followed systematically during 24 months post-operatively with regard to thyroid function. A thyroid remnant of at least 5 to 8 g was left in the majority of cases, and thyroid replacement was not given. Histopathological grading was performed on goitrous specimens with reference to lymphocytic infiltration. Thyroglobulin antibodies and thyroid microsomal antibodies were determined pre-operatively. Goitre resection provoked a high, but transient increase in serum thyroid stimulating hormone (TSH) levels with peak values 3 to 6 months after operation. Twenty-four months after surgery serum TSH values had normalized, but were still slightly elevated in patients with bilateral surgery and high lymphocytic infiltration, 9% of the patients. The concentration of serum free thyroxine index (FT4I) and serum total triiodothyronine (TT3) decreased after operation, but within reference range. Twenty-four months after surgery, serum FT4I was back to baseline values, while serum TT3 was still lowered compared to the pre-operative level. None of the patients developed overt hypothyroidism. Occurrence of circulating thyroid autoantibodies was not related to post-operative changes in thyroid parameters. We conclude that thyroid replacement therapy seems not to be indicated routinely following resection for non-toxic goitre, but precaution should be taken in case of bilateral resection and high lymphocytic infiltration of goitrous specimens.

Adolescent↗
PubMedDate not supplied

[Relationship between thyroid echogram and thyroid function in Hashimoto's thyroiditis].

Seventeen cases of untreated Hashimoto's thyroiditis were selected from the files of the Taipei Municipal Jen-Ai Hospital during the period from Jan. 1985 to Jan. 1986. All the cases were confirmed by a physical examination, determination of thyroid antibodies and fine needle aspiration cytology. Thyroid function was also determined. According to the echogenicity of the thyroid, they were divided into 2 groups, group A (8 cases) and group B (9 cases). In group A, homogeneous hypoechogenicity of the thyroid was noted and was lower than that of the adjacent muscles. In group B, heterogeneous echogenicity of the thyroid with equal or higher echogenicity than that of the adjacent muscles was noted. Group A showed a significantly lower serum T4, T3 and a higher serum TSH in comparison with group B. Five cases in group A presented hypothyroidism clinically while only 1 in group B presented. In conclusion, in the cases of Hashimoto's thyroiditis, the homogeneous hypoechogenicity of the thyroid echogram suggested the possibility of hypothyroidism. Statistically, the sensitivity was 83.3%, specificity 72.8%, positive prediction value 62.5% and the negative prediction value was 88.9%.

Adolescent↗
PubMed1983

Free thyroid hormone index, thyroid hormone/thyroxin-binding globulin ratio, triiodothyronine uptake, and thyroxin-binding globulin compared for diagnostic value regarding thyroid function.

The thyroid hormone/thyroxin-binding globulin (TBG) ratio and the free thyroid hormone index (FTI) were compared in 372 subjects classified according to age, sex, and biochemical and clinical findings. Age-related variations in thyroid function tests were investigated, as was the relationship between triiodothyronine uptake and TBG. Men, but not women, showed significant age-dependent changes in concentrations of thyroid hormones. FTI was as good as the thyroid hormone/TBG ratio in hyperthyroidism and was a better index of thyroid status in pregnancy, TBG deficiency, and hypothyroidism. In addition, the triiodothyronine uptake correlated extremely well with TBG (r = -0.95, p less than 0.001) and was very efficient in detecting decreased and significantly increased concentrations of TBG. I conclude that FTI is a better discriminator of functional status of the thyroid over a wider range of TBG values than is the thyroid hormone/TBG ratio. Further, the triiodothyronine uptake test produced diagnostic information equivalent to that of TBG estimation and thus should not be replaced in routine use.

Adolescent↗
PubMed1991

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

The concept of using thyroid-stimulating hormone (TSH) receptor antagonists in the management of Graves' disease is intriguing. Therefore, we investigated a TSH receptor antagonist derived from human chorionic gonadotropin (hCG) with respect to TSH receptor binding, adenylate cyclase activity, thyroid hormone release, and HLA class II antigen expression in vitro and in an in vivo model. A variant of hCG, asialoagalacto-hCG, like asialo-hCG and unlike hCG itself, inhibited both 125I-bTSH binding and cAMP response to bTSH in human thyroid membranes. However, like intact or deglycosylated hCG and unlike asialo-hCG, asialoagalacto-hCG displayed a limited affinity for hepatic asialoglycoprotein receptors, a likely marker for its in vivo turnover rate. It proved capable of inhibiting bTSH-stimulated thyroid hormone release in human thyroid slices as well as in the nude mouse bearing human thyroid transplants. It also prevented bTSH induced hypertrophy of transplanted thyrocytes. Further, HLA-DR expression induced by bTSH in the presence of gamma-interferon on human thyrocytes was inhibited. In conclusion, we present evidence that asialogalacto-hCG antagonizes bTSH actions on thyroid function and HLA-DR expression in human thyroid in vitro and, more importantly, in an in vivo model. Hence, the hCG variant described here or similar agents should warrant further exploration in the study and treatment of Graves' disease.

Adenylyl Cyclases↗
PubMed1975

[Clinical studeis on the regulatory system of thyroid hormone secretion and serum triiodothyronine. Part III. Studies on thyroid hormone change and its relationship when TSH in cases with subclinical hypothyroidism (Hashimoto's thyroiditis and 131I treated Graves' disease)].

Changes in thyroid hormone levels and their relationship with TSH in cases with Hashimoto's thyroiditis and 131I treated Graves' disease in subclinical hypothyroid state were investigated: 1) In 34 cases with Hashimoto's thyroiditis, TSH levels was 14.7 +/- 26.8 muU/ml (mean +/- s.d.), T3 144.5 +/- 33.6 Rg/100 ml; T4 6.7 +/- 2.4 MUG/100 ML; T3RU 25.4 +/- 3.2%; F.T.I. 2.0g +/- O.89; T3/T4 2.46+/- 1.04%. It was noted that TSH levels revealed significant positive correlation with T3/T4 (r=0.77); significant inverse correlation with F.T.I. (r= - 0.51); and non-significant inverse correlation with T3 levels (r= - 0.06). These results indicate that T3 might play a more important role than T4 in maintaining normal thyroid function (so-called T3 euthyroidism). This is probably based on metabolic disturbance of iodine which is common in Hashimoto's thyroid. In several cases with rather high normal basal T3 levels, no significant elevation in T3 was observed in spite of elevated TSH level following TRH administration. This might indicate that the thyroid is fully functioning and that no more reserve is left for the thyroid to respond further to elevated TSH. 2) In 30 cases with 131I treated Graves' disease, TSH concentration was 22.3 +/- 29.8 muU/ml (mean +/- s.d.); T3 100.7 +/- 35.4 ng/100 ml: T4 6.2 +/- 2.9 MUG/100 ML; T3RU 25.6 +/- 2.3%; F.T.I. 1.87 +/- 0.85; T3/T4 1.80 +/- 0.64. Significant inverse correlation was noted between TSH levels and F.T.I. as well as T3 levels. Although TSH levels showed significant positive correlation with T3/T4 (r=0.44), its degree of correlation was not as good as that with F.T.I. (r= - 0.71) and T3 (r= - 0.53). These results indicate that there is no preference in T3 production. From the responsiveness of thyroid and pituitary following TRH administration, assumption can be drawn that 131I treated Graves' patients, who became euthyroid, may in fact be on the way to hypothyroidism.

Follow-Up Studies↗
PubMed1991

Thyroid microsomal antigen in Graves' thyroid is not different from that in normal thyroid.

Differences from normal in microsomal antigen (M-Ag) may be involved in the development of autoimmune thyroid disease. We compared the M-Ag in Graves' thyroid immunologically and biochemically to that in normal thyroid. The concentration of M-Ag, measured with an enzyme-linked immunosorbent assay, was significantly greater in the Graves' microsomes than in normal microsomes. Binding of a patient's microsomal antibody to Graves' microsomes was completely inhibited when the serum was first incubated with normal thyroid microsomes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting were done with a monoclonal antibody to denatured M-Ag. In both Graves' and normal thyroids, M-Ag existed as 107-, 101-, and 95-kDa peptides. After incubation with V8 protease, the residual antigenic peptide had a molecular weight of less than 60,000 and after incubation with trypsin, 95- and 87-kDa peptides and several smaller antigenic peptides were found. There were no significant differences in the pattern of normal and Graves' microsomes after digestion. Two-dimensional gel electrophoresis of Graves' microsomes showed that the isoelectric point for the 107-kDa peptide was at pH 7.2; that for the 101-kDa peptide was at pH 6.2, and that for the 95-kDa peptide was at 6.5. These values were not different from those observed for normal microsomes. These results indicate that M-Ag in Graves' thyroid does not differ from that in normal thyroid, and that microsomal antibodies in autoimmune thyroid disease probably do no arise from differences in the antigen.

Autoantigens↗
PubMed1988

[Clinical studies on abnormal thyroid stimulators in patients with Graves' disease. I. A sensitive assay for thyroid-stimulating antibodies using cultured porcine thyroid cells and polyethylene glycol precipitation of serum].

The activities of thyroid-stimulating antibody (TSAb) in serum from patients with Graves' disease were measured by a sensitive assay, using cultured porcine thyroid cells and the precipitation from serum with polyethylene glycol (PEG), and the activities were compared with those of thyrotropin binding inhibitor immunoglobulin (TBII), measured by the commercial assay kit. Porcine thyroid cells after digestion were cultured for 15-18 hours with TSH of 1-10,000 microU/ml or the precipitations of sera from normal subjects and patients with Graves' disease or Hashimoto's thyroiditis, and then the cAMP levels in the culture medium were determined by the commercial RIA assay kit (Yamasa). The precipitation was obtained by adding 0.5 ml of 30% PEG solution to 0.5 ml serum, and was resuspended with 0.6 ml of Hanks' medium without NaCl, containing 1.5% bovine serum albumin, 20mM Hepes and 0.5 mM 3-isobutyl-1-methylxanthine. The precipitation contained about 85% of immunoglobulin and 63% of albumin of the original amount of the serum, as well as substantial TSH, when the original serum contained TSH more than 40 microU/ml. When the PEG precipitations from 10 normal subjects were incubated with the thyroid cells of 4 X 10(5) cells, the cAMP releases into the medium ranged from 83 to 124%, when the mean value was calculated as 100%. Therefore, the cAMP release of more than 130% of the amount released into the culture medium incubated with normal IgG was judged as positive TSAb activity. The minimum detectable quantities were regarded as about 5 microU/ml TSH equivalent. TSAb and TBII activities were detected in 48 (92%) and 50 (96%) of 52 patients with untreated hyperthyroid Graves' disease, respectively, and either TSAb or TBII activities were detected in 16 (80%) of 20 patients with Graves' disease maintained in a clinically euthyroid state by treatment with antithyroid drugs. TBII was positive in 10(50%) of these patients. Some patients showed distinct discrepancies in these two activities, although there was a significant positive correlation between TSAb and TBII activities (r = 0.53, p less than 0.01) in patients with untreated Graves' disease. In these patients, TSAb activities showed a significant positive correlation with values for 99mTc thyroid uptake, determined 30 min after the injection. However, they did not show any significant correlation with serum T4 or T3 concentrations. Similarly, TBII showed significant correlations with goiter size and 99mTc thyroid uptake. To conclude, the present assay for TSAb is sensitive and reproducible.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb).

In this paper, we report a 49-year-old female with subacute thyroiditis who had thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies (TSBAb) in serum. Although she was in the thyrotoxic phase and TSH was suppressed in May, 1990, her radioactive iodine uptake (RAIU) was not suppressed (35.5%) and a thyroid scan disclosed a diffuse goiter with no defect. Serum assays revealed the presence of TSAb, but TSBAb were negative. In August, 1990, the right lobe became undetectable by thyroid scan when the RAIU was 20.7% with the TSH level remaining suppressed. At that time, TSAb were negative, while TSBAb were positive. When the RAIU was 31.1% in October, 1990, both thyroid lobes became visible and the TSH level was normalized. TSBAb became negative, and although TSAb reappeared it later became undetectable. These results indicate that the changes in the patient's thyroid scan and RAIU were attributable to the presence of TSAb.

Autoantibodies↗
PubMed1982

Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells. III. Induction of thyroiditis by thyroid-sensitized T lymphoblasts.

During in vitro sensitization of CBA spleen lymphocytes on syngeneic monolayers of either thyroid epithelial cells (TEC) or fibroblasts, stimulation occurs, as assessed by thymidine incorporation and lymphoblast generation. When lymphoblasts generated on syngeneic TEC are injected either into thyroid lobes of intact CBA recipients or i.v., thyroiditis appears at least 21 days after injection. Thyroiditis is assessed by both optical and electron microscopic blind studies and by the presence of antibodies in the sera directed against mouse thyroglobulin. In contrast, control animals which received identical numbers of lymphoblasts generated on syngeneic fibroblasts behaved as normal. Thyroiditis was also induced using pure thyroid-sensitized T lymphoblasts. This is the first report showing the role of T lymphocytes in the induction of experimental autoimmune thyroiditis.

Animals↗