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Beta-endorphin and its congeners in rat pituitary and thyroid: effects of propylthiouracil and thyroid hormone administration.

Immunoreactive beta-endorphin (ir-beta EP) and immunoreactive N-acetyl-endorphin (ir-NacEP) have been demonstrated in the rat thyroid by specific RIA and characterized by reverse phase HPLC. In addition, pituitary and thyroid ir-beta EP and ir-NacEP levels have been determined after manipulation of the pituitary-thyroid axis by chronic (21 days) treatment with 1) propylthiouracil (PTU), 2) L-T4, 3) L-T3, or 4) T3 plus PTU. No difference in anterior pituitary or neurointermediate lobe ir-beta EP was seen between controls and treated groups (n = 8/group). In contrast, levels of ir-NacEP were markedly lower (P less than 0.01) in both hypo- and hyperthyroid groups than in controls, in both anterior pituitary and neurointermediate lobe. In the thyroid, levels of both ir-beta EP and ir-NacEP were profoundly depressed (P less than 0.01) in all treated groups, with no change in calcitonin levels, suggesting that the thyroid effect of PTU and T3/T4 may be specific for the synthesis, processing, and/or release of pro-opiomelanocortin derived peptides. The findings in this study suggest 1) that acetylation of pituitary and thyroid beta EP is similarly sensitive to PTU and thyroid hormone administration and 2) that in the thyroid, but not in the pituitary, both PTU and thyroid hormones markedly lower levels of pro-opiomelanocortin-derived peptides.

Acetylation↗

Thyroid hormone antibodies and Hashimoto's thyroiditis in mongrel dogs.

Abnormally elevated serum T3 concentrations measured by RIA were observed in 19 clinically euthyroid or hypothyroid mongrel dogs. The serum T4 concentrations in these sera were low, normal, or high. Measurement of the intensity of thyroid hormone binding to serum proteins was determined by equilibrium dialysis. A marked decrease in the percent free T3 was observed in these abnormal sera. Polyacrylamide gel electrophoresis, pH 7.4, of normal dog serum enriched with tracer 125I-labeled thyroid hormones demonstrated binding of [125I]T4 to transthyretin, thyroid hormone-binding globulin, and albumin and of [125I]T3 primarily to thyroid hormone-binding globulin. In all abnormal sera, polyacrylamide gel electrophoresis demonstrated strikingly higher binding of T3 to immunoglobulin (Ig). Eleven of 16 abnormal sera had minimal to moderate binding of T4 to Ig. The percent free T4 was lower only in dogs whose sera demonstrated markedly increased binding of T4 to Ig. All abnormal sera tested had positive antithyroglobulin antibodies, consistent with the diagnosis of autoimmune lymphocytic thyroiditis. As in humans, antibodies to thyroid hormones in dogs are more common in the presence of Hashimoto's thyroiditis and should be considered when elevated serum thyroid hormone concentrations are observed in the absence of clinical thyrotoxicosis. When an antibody to only one thyroid hormone is present, a marked discrepancy in the serum concentrations of T3 and T4 will be observed.

Animals↗

Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chickens.

The present study examines the role of thyroid cell injury in the initiation of autoimmune thyroiditis by iodine in Obese strain (OS) chickens, a strain genetically susceptible to spontaneous autoimmune thyroiditis. OS and normal strain chickens were placed on an iodine depletion regimen started in ovo. This regimen is known to prevent thyroiditis in OS chickens. The chickens were injected with NaI every 24 h for up to 7 days starting at 3 weeks of age. Both strains showed evidence of mild thyrocyte injury 12 h after NaI. However, significant and sustained infiltration, beginning 24 h after NaI, was seen only in the OS. The infiltrating cells were primarily mononuclear. Polymorphonuclear cells were not observed. Immunohistological analysis showed the infiltrate to be composed of CD8 T cells, CD4 T cells, B cells, and macrophages in the ratio 40:20:22:17. The infiltration was sustained and progressive for at least 7 days. Thyroid infiltration after NaI repletion was significantly reduced in OS chickens tolerized to thyroglobulin at hatching. Prior treatment with the antioxidant drug ethoxyquin completely prevented both the thyrocyte injury and the infiltration induced by iodine. Treatment with antioxidant drugs had no effect on the uptake and incorporation of iodine by the thyroid. In summary, 1) iodine caused thyrocyte injury in both OS and normal chickens. 2) The injury was followed by cellular infiltration in the OS but not in normal chickens. 3) The infiltration appeared to be immune mediated in being primarily lymphocytic and at least partially thyroglobulin sensitive. 4) Prevention of thyroid injury by antioxidant drug treatment also prevented infiltration. We conclude that thyroid cell injury may be an initial event in the induction of autoimmune thyroiditis by iodine.

Animals↗

Adsorption of thyroid-stimulating antibody (TSAb) of Graves' disease by homologous and heterologous thyroid tissue.

Immunoglobulin G purified from the serum of patients with Graves' disease, stimulated the thyroid of man, calf, and guinea pig (cAMP accumulation as the end-point) in vitro, and the thyroid of the mouse in vivo (LATS bioassay). The stimulatory effect on the thyroids of all four species was removed by adsorption of the immunoglobulin G to human thyroid membranes and was diminished to a proportionately similar degree by adsorption with bovine thyroid membranes. All activity, as assessed by stimulation of the human thyroid in vitro. was recovered from both human and bovine membranes by elution with 2 M NaSCN solution. The data support the concept that the thyroid-stimulating antibody of Graves' disease is homologous to a human thyroid antigen and, in some instances, cross-reacts with a similar antigen in the thyroid of a distant species and so stimulates the heterologous gland.

Adsorption↗

Thyroid-stimulating immunoglobulin bioassay using cultured human thyroid cells.

Modifications are described in the cultured thyroid cell cAMP assay for TSH which make it suitable for the measurement of thyroid-stimulating immunoglobulins. Comparison was made between this assay and two others measuring cAMP responsiveness in human thyroid tissue, namely the thyroid slice and thyroid plasma membrane adenylate cyclase assays, all performed with the same tissue sample. Of immunoglobulin G (IgG) samples from 7 unselected patients with untreated hyperthyroidism associated with Graves' disease, 5 produced significant stimulation of cAMP content in cultured thyroid cells when compared to pooled normal IgG. None of these 7 produced a statistically significant increase in thyroid slice cAMP content when assayed in triplicate, the same replicate number used in the cultured thyroid cell assay. Similarly, none of the same Graves' IgG samples produced significant stimulation (vs. control IgG) in the membrane adenylate cyclase assay, in which sensitivity to TSH stimulation was very poor. With a scaled-down modification of the assay using microtiter wells and acetylation to enhance detection of cAMP in the RIA, significant TSI activity was observed in 15 of 18 (83%) IgG samples from patients with untreated Graves' disease. The data indicate the excellent sensitivity and precision of the thyroid cell cAMP assay, as well as its convenience.

Biological Assay↗

Thyroid nodules in the follow-up of irradiated individuals: comparison of thyroid ultrasound with scanning and palpation.

In 1974 we began a prospective study of a cohort of 4296 individuals exposed to therapeutic head and neck irradiation during childhood for benign conditions. To define the role of thyroid ultrasonography in following irradiated individuals, we studied a subgroup of 54 individuals. They all had been screened between 1974-1976 and had normal thyroid scans and no palpable nodules at that time. Thyroid ultrasonography, thyroid scanning, physical examination, and serum thyroglobulin measurements were performed. One or more discrete ultrasound-detected nodules were present in 47 of 54 (87%) subjects. There were a total of 157 nodules, 40 of which were 1.0 cm or larger in largest dimension. These 40 nodules occurred in 28 (52%) of the subjects. Thirty (75%) of these 1.0-cm or larger nodules matched discrete areas of diminished uptake on corresponding thyroid scans. The 10 that did not match (false negative scans for > or = 1.0-cm nodules) were the only nodules of this size in 7 subjects. Of 11 nodules 1.5 cm or larger, only 5 were palpable. Serum thyroglobulin correlated to the number (P = 0.04; r2 = 0.10), but not the volume of the thyroid nodules (P = 0.07; r2 = 0.08). We conclude that thyroid nodules are continuing to occur and are exceedingly common in this irradiated cohort of individuals. The results confirm that thyroid ultrasonography is more sensitive than physical examination and scanning. However, thyroid ultrasound is so sensitive and nodules so prevalent that great caution is needed in interpreting the results.

Child↗

Thyroid-specific expression and cyclic adenosine 3',5'-monophosphate autoregulation of the thyrotropin receptor gene involves thyroid transcription factor-1.

The chimeric chloramphenicol acetyltransferase (CAT) construct, pTRCAT5'-199, containing the TSH receptor (TSHR) minimal promoter, -199 to -39 base pairs (bp), exhibits the thyroid specificity and TSH/cAMP autoregulation evident in TSHR gene expression. The present report shows that a cis-acting element between -189 and -175 bp, which binds thyroid transcription factor-1 (TTF-1), is involved in both activities. The 22 bp between -199 and -178 contains a positive element important for expression of the TSHR minimal promoter in rat FRTL-5 thyroid cells. DNAase I footprinting shows that extracts from functioning FRTL-5, but not non-functioning FRT thyroid or Buffalo rat liver (BRL) cells, protect a region between -189 and -175 bp. The protection is duplicated by TTF-1, and the protected element has only a two-base mismatch from the consensus TTF-1 element identified in the thyroglobulin (TG) and thyroid peroxidase minimal promoters. Gel mobility shift analyses reveal that FRTL-5 thyroid cell nuclear extracts form a specific protein/DNA complex with this region, which is prevented by the TTF-1 binding element from the TG promoter; FRT and BRL cell nuclear extracts do not have TTF-1 and do not form this complex. A role for the TSHR/TTF-1 binding element in thyroid-specific expression of the TSHR gene is evidenced as follows. Overexpression of TTF-1 in FRT or BRL cells, which have no TTF-1, increased the activity of pTRCAT5'-199, but not pTRCAT5'-177, which has no TTF-1 binding element. A nonsense mutation of the TTF-1 binding element eliminated TTF-1-induced activation of TSHR promoter activity in FRT or BRL cells and reduced TSHR promoter activity in FRTL-5 thyroid cells. In contrast, mutation of this element to the TTF-1 consensus sequence of the TG or thyroid peroxidase promoter had no significant influence on TSHR promoter activity. The activity of the TSHR/TTF-1 binding element requires a functioning cAMP response element (CRE). Thus, TTF-1 activity is lost when the CRE site is mutated to a nonfunctional, nonpalindromic sequence; it is, in contrast, maximized when CRE activity is maximized by its mutation to a consensus AP1 element. TTF-1 phosphorylation is important for binding and activity. Thus, binding of TTF-1 to the TSHR/TTF-1 element is phosphatase-sensitive and is increased by treating nuclear extracts with the catalytic subunit of protein kinase A. Overexpression of the catalytic subunit of PKA enhances TTF-1-increased activity of the TSHR minimal promoter.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Up-regulation of cyclooxygenase-2 expression in lymphocytic thyroiditis and thyroid tumors: significant correlation with inducible nitric oxide synthase.

To cast light on relations of cyclooxygenase-2 (COX-2) expression to lymphocytic thyroiditis and thyroid tumorigenesis, protein levels were immunohistochemically assessed and compared with inducible nitric oxide synthase (iNOS) in a total of 181 cases: follicular adenoma, 23; well-differentiated papillary carcinoma, 85; poorly differentiated papillary carcinoma, 25; anaplastic carcinoma, 7; and follicular carcinoma, 41. In addition, 72 specimens of normal follicular epithelia and 36 of lymphocytic thyroiditis were used as control samples. Immunohistochemical results were confirmed in 2 cases each of normal thyroid, lymphocytic thyroiditis, and well-differentiated and poorly differentiated papillary carcinoma, by Western blotting assay. Stepwise increments in overexpression of COX-2 and iNOS were revealed in epithelial cells of lymphocytic thyroiditis, follicular adenoma, and papillary carcinoma; normal thyroid epithelium showed little expression. A significant positive correlation between the 2 enzymes was found with all cases. Enhanced expression of both COX-2 and iNOS suggests important roles in the inflammatory processes underlying lymphocytic thyroiditis and thyroid tumorigenesis.

Adenoma↗

New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid.

BACKGROUND: The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals. METHODS: We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T(4) and FT(4)), and total and free triiodothyronine (T(3) and FT(3)) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison. RESULTS: The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P <0.0001). Use of oral contraceptives was a significant predictor for variation in T(4) concentrations (P <0.001). Age and oral contraceptives were independently associated with T(3) variations (P <0.05). For FT(4) vs FT(3) variation, gender and (inversely) age (P <0.01) were independent modulating factors. CONCLUSIONS: The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.

Adolescent↗

[Clinical studies on autoimmune mechanisms of the thyroid Part II. Leucocyte migration inhibiton studies in Hashimoto's thyroiditis and in Graves' disease (author's transol)].

The Leucocyte migration inhibiton test (LMT) using the agaraose plate technique according Clausen was performed in 19 patients with Hashimoto's thyroiditis, 23 patients with Graves' disease, and in 17 normal subjects. A series of leucocyte suspensions was preincubated at 37 degrees C for 30 min. with crude thyroid extract (Crude), purified thyroglobulin (Tg) and thyroid microsomes (Micr) in concentrations of 500, 300 and 100 muml, respectively together with phosphate buffer saline (PBS) as the control. Then, each of the aliquots of 7 mul of leucocyte suspension 1.5 million leucocytes, preincubated with various antigens of PBS, was placed into 4 wells, 2 in each of 2 agarose plates, followed by a 2nd incubation for 24 hours at 37 degrees C, in 2 per cent CO2 with 98 per cent atomospheric air, resulting in a pH of between 7.2 and 7.4. After the incubation, the migration areas were studied and measured by planimetry. The degree of migration inhibition was expressed as a migration index (MI); that is, the ratio of the average extent of migration of the leucocytes cultured with antigens to that of control. The MI values for normal subjects against Crude, Tg and Micr were 97.6 +/- 6.8 (mean +/- S.D)%, 97.8 +/- 4.2%, and 95.5 +/- 5.3%, respectively. Low MI values, below 2 S.D. of the normal, were regarded as positive results. The rate of positive LMT in patients with Hashimoto's thyroiditis were 32%, 46% and 31% against Crude, Tg and Micr, respectively. In Graves' disease, they were 35%, 50% and 41% for the same antigens, respectively. In 68--68% of patients with Hashimoto's thyroiditis or Graves' disease, positive LMT was at least shown with one of the three antigens. In Graves' disease, there was no correlation between MI values and the presence of long acting thyroid stimulator (LATS). In untreated patients with Hashimoto's thyroiditis and Graves' disease with a short clinical course, the migration inhibiton factor against Tg or Micr was found to be positive in a remarkably high rate. On the other hand, the levels of circulating antibodies in the serum tended to show high titers in patients with long duration, comparing with those with short duration. From the histological findings obtained by needle biopsy of thyroid tissue, grade of lymphocytic infiltration was found to be significantly correlated with the degree of reduction in MI values. From these observations, it is concluded that MIF against Tg can easily be detected by the agarose plate technique and that cellular immunity may play a more important role in the initial phase of autoimmune thyroid diseases than the later phase, in which the serum levels of circulating antibodies are becoming predominant.

Adult↗

Stimulation of thyroidal iodothyronine 5'-monodeiodinase by long-acting thyroid stimulator (LATS).

To evaluate the effect of long-acting thyroid stimulator (LATS) on thyroid iodothyronine monodeiodinating activity, we have studied the in vitro conversion of T4 to T3 by mouse thyroid homogenate comparing tissue from LATS treated (0.1 ml LATS(+) serum, ip, for 3 days) with tissues from LATS(-) Graves' disease patients' serum or normal serum treated controls. Five out of seven LATS(+) sera were shown to stimulate the T4 5'-deiodinase significantly in mouse thyroid. There was no significant correlation between LATS titre and deiodinase activities in the different sera tested. To compare the effect of LATS and TSH (0.2 IU, ip daily), studies were carried out from 12 to 72 h. LATS had a similar latency of 12 h on the stimulation of thyroid deiodinase compared to TSH as reported earlier. However, the conversion activities reached a plateau by 12 h after LATS treatment, while it continued to rise upon daily TSH injection from 24 to 72 h. In addition, TSH caused a marked reduction of thyroid protein and an early peaking in serum T3 and T4 at 12 h, whereas LATS caused no detectable change in thyroid protein and a gradual rise in circulating T3 and T4. The kinetic analysis indicated that LATS-mediated stimulation of T4 5'-deiodinase was, similar to TSH, associated with an increase in maximum velocity (Vmax were 139, 208 and 505 pmol/mg protein/30 min respectively in control, LATS and TSH-treated animals) without a demonstrable change in the apparent Km (approximately 2.0 microM for T4). The present study demonstrated that some LATS-rich sera stimulate thyroid T4 to T3 conversion in mouse. It provides an insight into the mechanism of increased T3 secretion from Graves' thyroid glands.

Animals↗

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases.

OBJECTIVE: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B- and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor-ligand pair in thyroid autoimmunity. METHODS: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. RESULTS: We found no differences between the percentages of peripheral blood CXCR5+ T- and B-cells in GD patients (n=10) and healthy controls (n=10). In GD patients, the number of memory CD4+ cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroid-derived (18+/-3%) compared with peripheral blood T-lymphocytes (8+/-2%). The highest CXCL13 mRNA levels were found in HT (n=2, 86.1+/-1.2 zmol (10(-21) mol) cDNA/PCR) followed by GD tissues (n=16, 9.6+/-3.5). Only low amounts were determined in thyroid autonomy (TA) (n=11) thyroid tissues, irrespective of whether the autonomous nodule (0.5+/-0.1) or the surrounding normal tissue (1.8+/-0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1+/-6.8; GD: 17.4+/-10.6; TA(nodule): 0.8+/-0.5; TA(normal): 4.4+/-3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. CONCLUSIONS: CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity.

Adult↗

Thyroid hormone receptor beta mutations in the 'hot-spot region' are rare events in thyroid carcinomas.

Thyroid cancer constitutes the most frequent endocrine neoplasia. Targeted expression of rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) and V600E V-raf murine sarcoma viral oncogene homolog B1 (BRAF) to the thyroid glands of transgenic mice results in tumours similar to those of human PTC, providing evidence for the involvement of these oncogenes in PTC. Kato et al. developed a mouse model that mimics the full spectrum of the human follicular form of thyroid cancer (FTC). FTC rapidly develops in these mice through introduction of the thyroid hormone receptor beta (THRB)(PV) mutant on the background of the inactivated THRB wt locus. Our aim was to verify if, in the context of human follicular thyroid carcinogenesis, THRB acted as a tumour suppressor gene. We screened for mutations of the THRB gene in the hot-spot region, spanning exons 7-10, in 51 thyroid tumours and six thyroid cancer cell lines by PCR and direct sequencing. We did not find mutations in any of the tumours or cell lines analysed. Our findings suggest that, in contrast to the findings on the THRB-mutant transgenic mice, THRB gene mutations are not a relevant mechanism for human thyroid carcinogenesis.

Carcinoma, Papillary↗

Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells.

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.

Adult↗

The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto's thyroiditis.

Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 micro g/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 micro IU/mL at the baseline, 25.66 +/- 70.79 micro IU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 micro IU/mL vs. 123.14 +/- 156.51 micro IU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.

Adult↗

[Autoimmune thyroid diseases complicated with reversible changes of thyroid function].

Autoimmune thyroid disease (AID) with reversible thyroid dysfunction was classified mainly by etiology. Hashimoto thyroiditis itself, pregnancy, cytokine therapy and various drugs, iodine-rich food and AID with TSH receptor antibody (TRAb) were main items. Silent or painless thyroiditis which was termed destructive thyroiditis occurs without clear cause or after adrenectomy for Cushing syndrome. Abnormal human chorionic gonadotropin (hCG) rarely causes transient thyrotoxicosis at early phase of pregnancy and postpartum thyroiditis which has similar symptom as silent thyroiditis is relatively common disorders. Thyroid dysfunction of patients with both TRAb (TSAb and TSBAb) is pathophysiologically unknown and the detection of both antibodies in a patient serum is difficult methodologically. We developed the highly sensitive TSAb assay by patients' IgG precipitated by high concentration PEG (22.5%) using porcine thyroid cell. This assay is also useful for detection of the coexistence cases of TSAb and TSBAb.

Autoimmune Diseases↗

Primary lymphoma of the thyroid, the association with Hashimoto's thyroiditis.

This paper reviews the cases of thyroid lymphoma seen at one centre to assess the relationship between autoimmune thyroiditis and the subsequent development of thyroid lymphoma. Twenty two cases of thyroid lymphoma were seen over a 10 year period; 5/22 (23%) had previously been diagnosed as having Hashimoto's thyroiditis. The series comprised 18 women and four men; mean (range) age at presentation was 64 (26-85) years. All patients presented with a rapidly enlarging goitre and 13/22 (59%) underwent surgical excision prior to diagnosis of lymphoma. Nineteen of 22 (86%) patients underwent radiotherapy. The 5-year mortality for stage IE disease was 43%, survival appeared to be unrelated to previous Hashimoto's thyroiditis or to surgical resectability. The histological differentiation between pre-existing thyroiditis and thyroid lymphoma is often difficult and may lead to an underestimate in the reporting of the association. A prospective study of serial autoantibody assays in patients with Hashimoto's thyroiditis may be useful in predicting the onset of lymphomatous change in this condition.

Adult↗