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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↗
PubMed1998

Use of radioactive iodine for thyroid remnant ablation in well-differentiated thyroid carcinoma to replace thyroid reoperation.

Complete thyroidectomy was recommended for patients with well-differentiated thyroid carcinoma to remove any potential residual contralateral cancer tissue and to facilitate detection of metastatic lesions by radioactive iodide (131I). Unfortunately, 8-32% incidence of severe complications were noted after reoperation. At present, there are still not enough data about the ablative effect of 131I for such conservative surgical treatment of well-differentiated thyroid cancers. The major goal of the present study was to examine the effects of 311I for ablation of thyroid remnants in order to obviate the severe complications associated with reoperation. From January 1977 to December 1995, 210 papillary or follicular thyroid carcinoma patients received subtotal thyroidectomy or lobectomy. After the operation, 46 of the 210 patients received 131I for remnant ablation. At doses of > or = 30 mCi 131I, 38 thyroid remnants were successfully ablated; 25 of 38 (65.8%) patients successfully ablated patients received 30 mCi 131I one-four times. Five patients expired during the follow-up period, including two follicular carcinoma patients who were misinterpreted as having benign lesions in the first operation. Patients in the overall failure versus success group for thyroid remnant ablation revealed increased age, histopathology of follicular carcinoma, higher postoperative 131I uptake in the neck bed, higher postoperative thyroglobulin levels, bigger tumor size, and higher mortality. In conclusion, repeated 30 mCi 131I treatments were adequate for most thyroid remnant ablations following subtotal thyroidectomy or lobectomy in well-differentiated thyroid cancer patients. Misinterpretation of follicular cancer as benign lesions and unresectable tumor comprised the main reasons for mortality.

Adenocarcinoma, Follicular↗
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↗
PubMed1995

Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.

To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.

Animals↗
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↗
PubMed1998

Hyperfunctioning thyroid adenoma concomitant with papillary thyroid carcinoma, follicular thyroid adenoma and primary hyperparathyroidism.

A case of 67-year-old woman with hyperthyroidism due to functioning thyroid adenoma is reported. The patient had concomitant follicular thyroid adenoma and primary hyperparathyroidism in addition to functioning adenoma. Histological examination of the excised thyroid tissue revealed occult papillary carcinoma within a functioning adenoma. Genetic analysis of such tumors indicated that functioning adenoma and papillary carcinoma may be etiologically independent. There have been a number of case reports on the coexistence of functioning thyroid adenoma and thyroid cancer or hyperparathyroidism, but none of the studies had examined the etiologic relationship of these lesions on a genetic basis. Furthermore, to our knowledge, this is the first report of the concurrence of four tumors in the neck, functioning thyroid adenoma, papillary thyroid carcinoma, follicular thyroid adenoma and parathyroid adenoma.

Adenoma↗
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↗
PubMed1977

Thyrotropin binding and long acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates.

The ability of various thyroid subcellular fractions to bind [125I]iodo TSH and to absorb long-acting thyroid stimulator (LATS) and thyroid stimulating immunoglobulins (TSI) activities was examined. Membranes purified from thyroid homogenates or isolated thyroid cells absorbed LATS/TSI activities and specifically bound [125I]iodo TSH. Purified thyroglobulin, nuclei, mitochondria and ribosomes did not bind [125I]iodo TSH nor did they absorb LATS/TSI activities. Cell sap obtained by gentle lysis of isolated thyroid cells failed to absorb LATS/TSI activities and to bind labeled hormone. However, freeze-thawing of the cells fragmented the membranes, releasing [125I]iodo TSH binding as well as LATS/TSI absorbing activities into the soluble (cell sap) fraction. The results suggest that the LATS/TSI antigen is of cell surface origin, includes the TSH receptor or larger membrane fragments containing the receptor, and that its release into the soluble fraction is due to the fragmentation of the thyroid membrane during homogenization and preparative procedures.

Animals↗
PubMed1991

Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases.

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.

Adolescent↗