SEARCH · Search PubMed

Results for “thyroiditis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources

PubMed1990

Strain-specific determination of the degree of thyroid cell MHC class II antigen expression: evaluation of established Wistar and Fisher rat thyroid cell lines.

The major histocompatibility complex (MHC) genes, primarily of the MHC class II region, are linked to increased susceptibility to autoimmune thyroid disease in animals and humans. The quantity of MHC class II antigens that are expressed on the appropriate cell surface, as well as their allotype, are of vital importance to immune function. We have, therefore, compared MHC class II (RT1.D) gene activation in a newly available Wistar rat thyroid (WRT) cell line (a thyroiditis-susceptible strain) with a cloned cell (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) (a thyroiditis-resistant strain) to determine differences in their degree of MHC class II gene activation and antigen expression. There was no detectable constitutive MHC class II antigen or RT1.D alpha-chain messenger RNA expression in either WRT or 1B-6 cells. Cultures of both cells expressed MHC class II gene induction in response to recombinant rat gamma-interferon (gamma IF). After 72 h of exposure to 25 U/ml gamma IF, over 80% of WRT cells expressed class II antigen, detected by flow cytometric assessment, as compared to only 15% of 1B-6 cells. This earlier and greater expression of MHC class II antigen was reflected in the RT1.D alpha-chain mRNA responses with peak levels in WRT cells after only 24 h of exposure to gamma IF, a period in which 1B-6 cells showed only minor increases in mRNA. To examine whether these differences in class II MHC expression were thyroid-cell specific, primary pulmonary fibroblast lines from Wistar and Fisher rats were developed and a similar, although less marked, variation in susceptibility to gamma IF was observed. Hence, those rats strains that are resistant to autoimmune thyroid disease exhibit a fundamental difference in their MHC class II gene responsiveness to cytokines, which may contribute to their disease susceptibility profiles.

Animals↗

PubMed1992

Thyroid hormone receptors and 3,5,3'-triiodothyronine biological effects in FRTL5 thyroid follicular cells.

Specific thyroid hormone (T3) receptors are present in thyroid follicular cells, including the rat FRTL5 clonal line, but little is known about the effects of T3 on the growth and differentiated function of the thyroid. Unlike primary cultures of animal or human thyroid cells, FRTL5 do not secrete appreciable amounts of thyroid hormones. We now have studied the effects of T3 by itself and in combination with TSH and insulin-like growth factor-I (IGF-I) on [3H]thymidine incorporation into DNA, iodide uptake, and cAMP production in FRTL5. We also have investigated the expression of different c-erbA mRNAs in these cells. Specific binding of T3 to FRTL5 cell nuclei in intact cells occurred with a binding capacity of 0.1-0.15 ng T3/mg DNA and an apparent Kd of 0.4 nM. Using an RNase protection assay on total cellular FRTL5 RNA and specific cRNA probes, we demonstrated the presence of c-erbA alpha and -beta mRNAs, both encoding T3 receptors. Biological effects were assessed in serum-free medium or buffer containing 0.1% BSA after maintaining quiescent culture of cells for at least 5 days in hormone-free medium containing 5% calf serum. T3 alone stimulated a dose-dependent increase in [3H]thymidine incorporation that reached a plateau at 188% of the control value at 10 nM T3. At 10(-11) M TSH, T3 potentiated TSH-stimulated [3H]thymidine incorporation (2.2-fold), but at TSH concentrations greater than 5 x 10(-11) M, T3 had no effect or reduced the response to TSH. T3 potentiated the [3H]thymidine response to 2 and 10 ng/ml IGF-I by 1.5- to 1.7-fold. T3 alone had no effect on iodide uptake, but attenuated iodide uptake stimulated by TSH. T3 was more potent in inhibiting TSH-stimulated iodide uptake than in enhancing TSH-stimulated DNA synthesis. T3 did not affect either basal or TSH-stimulated cAMP accumulation. Thus, in FRTL5 thyroid follicular cells 1) T3 receptors are expressed, as measured by direct binding assays and by the expression of c-erbA mRNAs; and 2) T3 acts as a growth factor and weak antidifferentiation factor. We suggest that T3 may modulate the actions of TSH and growth factors in thyroid epithelium.

Animals↗

PubMed1998

Retrovirus-mediated suicide gene/prodrug therapy targeting thyroid carcinoma using a thyroid-specific promoter.

To develop gene therapy targeting thyroid carcinoma, the recombinant retrovirus (LNTGTK) carrying herpes simplex virus thymidine kinase (HSV-TK) gene under the control of thyroglobulin (TG) promoter was constructed and its efficacy was investigated in 3 thyroid cell lines; a differentiated normal rat thyroid cell line (FRTL5), malignant rat thyroid carcinoma cells derived from FRTL5 (FRTC) and a human anaplastic thyroid carcinoma cell line (FRO). TG mRNA was detected by Northern blot analysis in FRTL5 cells and by RT-PCR in FRTC cells when cultured with 2 U/L TSH and its expression levels were decreased by TSH withdrawal. However, either methods revealed no TG expression in FRO cells. In vitro cytotoxic assays demonstrated TG expression status-dependent cell killing by transduction of LNTGTK followed by ganciclovir (GCV) treatment. Thus, LNTGTK transduction increased the GCV sensitivity approximately 13,000- and approximately 160-folds in the presence of TSH and approximately 4- and approximately 27-folds in the absence of TSH in FRTL5 and FRTC cells, respectively. In contrast, there was no difference in the GCV cytotoxicity between parental and transduced FRO cells. Significant growth inhibition, but not complete eradication, of transduced FRTC cells was observed in in vivo subcutaneous tumor models of nude mice. These results demonstrate that retrovirus-mediated transduction of HSV-TK gene under the control of the TG promoter confers the GCV sensitivity selectively to TG-expressing thyroid cells. This system may therefore be feasible for gene therapy targeting TG-expressing thyroid carcinomas.

Animals↗

PubMed2004

Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders.

The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.

Adult↗

PubMed2004

Medical cure of plasma cell granuloma of the thyroid associated with Hashimoto's thyroiditis: a case report and review.

Plasma cell granuloma (PCG) is a rare, benign inflammatory tumor composed of myofibroblasts, abundant plasma cells, and lymphocytes combined with collagen. A thyroid localization of PCG is extremely rare, and surgical therapy is indicated. We report the case of a 35-yr-old woman with a thyroid PCG, associated with Hashimoto's thyroiditis, that was responsible for tracheal compression. Surgery was performed, but the thyroid could not be removed because of the fibrotic process. The patient was treated with corticosteroids and immunosuppressive therapy. Dyspnea and dysphagia improved within 1 month, whereas thyroid volume returned to normal within 3 yr. We also review other reports of thyroid PCG in the literature and discuss the differential diagnosis and treatment. Although the use of immunosuppressive therapy has never been reported for thyroid PCG until now, this treatment may represent a good alternative to surgery in life-threatening, unresectable PCG.

Adrenal Cortex Hormones↗

PubMed1975

Patterns off recovery of the hypothalamic-pituitary-thyroid axis in patients taken of chronic thyroid therapy.

To determine the patterns of recovery of the hypothalamic-pituitary-thyroid axis following long-term thyroid hormone therapy, TRH tests were performed on 8 euthyroid nongoitrous patients, 5 euthyroid goitrous patients, and 5 hypothyroid patients while they were taking full doses of thyroid hormone and 3, 7, 10, 14, 17, 21, 28, 35, 42, 49, and 56 days after stopping it. Serum TSH, T3, and T4 were measured before and at multiple intervals over a 4-h period after giving 500 mug TRH iv. In euthyroid non-goitrous patients, the mean duration of suppressed TSH response to TRH (maximum deltaTSH less than 8 muU/ml) was 12 +/- 4 (SE) days after stopping thyroid hormone and the mean time to recovery of normal TSH response to TRH (maximum deltaTSH greater than 8 muU/ml) was 16 +/- 5 days. None of the euthyroid nongoitrous patients ever hyperresponded to TRH; their average maximal deltaTSH was 24.5 +/- 2.2 muU/ml. Serum T4 fell below normal in 4 euthyroid non-goitrous patients, reaching lowest values at 4 to 28 days. While serum T4 was low, deltaTSH was subnormal. Normal increments of T4 and T3 after TRH occurred at 19 +/- 5 and 22 +/- 6 days, respectively. In the 5 goitrous patients, patterns of recovery of pituitary and thyroid function assessed by the same parameters were much less consistent. In the 5 hypothyroid patients, the mean duration of suppressed basal TSH and suppressed deltaTSH was 13 +/- 3 days; mean time to attain a supranormal basal TSH (greater than 8 muU/ml) was 16 +/- 4 days and to reach a supranormal deltaTSH (greater than 38 muU/ml) after TRH was 29 +/- 8 days. Following prolonged thyroid therapy in euthyroid patients, recovery of normal TSH responsiveness to TRH preceded recovery of the normal T3 and T4 response to TRH by 3 to 6 days. Basal serum TSH may be used to differentiate euthyroid from hypothyroid patients 35 days after withdrawal of thyroid therapy; the response to TRH does not improve this differentiation.

Adolescent↗

PubMed1982

Evolution of thyroid 127I stores measured by X-ray fluorescence in subacute thyroiditis.

Evaluation of the thyroid iodine content by x-ray fluorescence was performed in 13 patients throughout the course of subacute thyroiditis. In the initial hyperthyroid phase of the disease, the iodine stores of the thyroid were not completely depleted. The iodine content (6.5 +/- 3 mg) was about 2.5 times lower than normal values when thyroiditis had developed in a normal thyroid (10 patients); in 3 patients with goiter, it was elevated (29.6 +/- 6.7 mg) but was still within the normal range of euthyroid goitrous patients. After clinical remission, the iodine content of the gland increased only in two patients (+105% and +43% over the initial value, respectively). For the other patients, the iodine content decreased (from -5% to -100% of the initial value). Restoration of iodine stores occurred subsequently and appeared to be a slow and progressive phenomenon; in six patient, the iodine content was still below normal values 12 months after clinical remission (6.6 +/- 1.6 mg). These data suggest that the course of subacute thyroiditis might be longer than would appear from the clinical data, the hormonal assays, or the radioactive thyroid uptake data.

Adrenal Cortex Hormones↗

PubMed1986

Detection of autoantibodies to thyroid peroxidase in autoimmune thyroid diseases by micro-ELISA and immunoblotting.

Serum autoantibodies to thyroid peroxidase (TPO) in patients with thyroid autoimmune diseases were studied by micro-ELISA and immunoblotting. Twenty-four patients, 15 with Graves' disease and 9 with Hashimoto's thyroiditis, whose serum titers were greater than 3200 on the microsomal hemagglutination test (except for 1 patient with a titer of 800) had autoantibodies to TPO. Both immunoglobulin G and M classes of autoantibodies were detected, with the former being more prominent. When TPO and thyroid microsomes were used as a target in a competitive binding inhibition test, the results suggested that TPO was a major thyroid microsomal antigen. On the other hand, immunoblotting analysis showed 3-4 bands in the 45-60K region stained by patients' sera in addition to human TPO with mol wt of 100K and 107K; only the latter 2 bands stained with antiporcine TPO antibody. In the majority of sera, TPO bands were clearer than others, although some sera showed the clearest band with a mol wt of 55K. These results indicate that patients with autoimmune thyroid disease often have autoantibodies to TPO that can be detected by micro-ELISA and immunoblotting, and that TPO is a major component of the thyroid microsomal antigen.

Animals↗

PubMed1993

Reconstitution of severe combined immunodeficient mice with intrathyroidal lymphocytes of thyroid xenografts from patients with Hashimoto's thyroiditis.

Thyroid tissues from patients with Hashimoto's thyroiditis (HT) have been xenografted to both severe combined immunodeficiency (SCID) mice and nude mice to study the intrathyroidal lymphocytes which were expected to migrate from the xenografts in the SCID mice. Peripheral blood mononuclear cells from HT, Graves' disease, and normal donors have also been separately engrafted. SCID mice, but not nude mice with HT thyroid grafts produce human immunoglobulins. More immunoglobulin G (IgG), but less IgM and IgA is produced in SCID mice with HT thyroid grafts (SCID-TH), compared to SCID mice injected with peripheral blood mononuclear cells from patients with HT or normal donors (SCID-PB), suggesting that different B cell subpopulations were active in the SCID-PB vs. SCID-TH. Production of IgG by SCID-PB and SCID-TH was maintained 6 weeks after engraftment, and decreased thereafter. SCID mice but not nude mice grafted with HT thyroid tissue produce antibodies to thyroglobulin and thyroperoxidase. Lymphocytes within intact HT thyroid grafts persist in SCID mice, and migrate to the spleen, whereas human lymphocytes do not survive in the thyroid grafts or other tissues of the nude mouse. In 6 weeks, the xenografts in nude mice became histologically normal. In contrast, xenografts from SCID mice showed more marked inflammatory changes than in the original human lesion, although the ratio of T/B cells is unchanged. This worsening of the lesion may relate to the increase in activation of the T-lymphocytes.

Animals↗

PubMed1993

T-cell receptor V gene use in autoimmune thyroid disease: direct assessment by thyroid aspiration.

We have examined the hTcR V gene family use of T-cells present in the aspiration thyroid biopsy specimens of patients with hyperthyroid Graves' disease (n = 8) and Hashimoto's autoimmune thyroiditis (n = 5). Nine of the 13 specimens had cytologically identified thyroid follicular cells, and 12 of the 13 contained human thyroglobulin-specific mRNA, confirming successful sampling. Of 18 hTcR V alpha and 19 hTCR V beta gene families tested for in the individual aspirates, a mean +/- SEM of 6.8 +/- 0.9 V alpha and 9.6 +/- 1.4 V beta gene families were present in the Graves' aspirates, while 12.2 +/- 1.7 and 16.8 +/- 0.4 V alpha and V beta gene families were present in the aspirates of patients with Hashimoto's thyroiditis. These samples, which offer a window onto the natural history of autoimmune thyroid disease, demonstrate significant hTcR V alpha and beta gene restriction in hyperthyroid Graves' disease, but much less restriction of both V alpha and V beta gene families in Hashimoto's disease. Such data extend our earlier information based only on examination of highly selected surgical specimens of patients with autoimmune thyroid disease to the much more typical patient. We conclude that hTcR V gene restriction of varying degrees is present in the majority of patients with autoimmune thyroid disease, but appears to be more easily detected in Graves', rather that Hashimoto's, disease.

Adult↗

PubMed1997

Thyrotropin-receptor and thyroid peroxidase-specific T cell clones and their cytokine profile in autoimmune thyroid disease.

We studied the cytokine profile and the immune responses to thyroid antigens of specific T cell clones (TCC) isolated from patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD). Antigen-specific TCC were reactive to thyroid peroxidase (TPO), thyroglobulin (Tg) or human recombinant TSH-receptor extracellular domain (TSH-R), and/or their respective peptides. Of the 43 clones derived from HT patients, 65% were reactive to TPO, and 59% of the 32 clones derived from GD patients were reactive to TSH-R. TPO epitopes 100-119 and 625-644 were recognized by 75% of HT-derived clones, whereas TSH-R epitopes 158-176, 207-222, and 343-362/357-376 were recognized by 85% of GD-derived TCC. The TCC were classified according to their cytokine profile into T helper cell (Th)0 [secreting interleukin (IL)-4, IL-5, interferon (IFN)-gamma], Th1 (secreting IFN-gamma) and Th2 (secreting IL-4 and/or IL-5). Tumor necrosis factor-beta and IL-10 were produced by all subsets. The specific TCC were predominantly Th1-like cells in HT, and were Th0- and Th1-like cells in GD. Fifty three percent of Th0 clones were derived from GD patients and were reactive to TSH-R, whereas 50% of Th1 clones were derived from HT patients and were reactive to TPO or Tg. Most Th2 clones (82%) were reactive to TPO and were established from peripheral blood. All these clones produced IL-5, and 64% produced IL-4 and IL-10. Interestingly, IFN-gamma was highly produced by TPO- or Tg-specific clones established from HT thyroid tissue. These results confirm at the clonal level our previous studies regarding T cell epitopes on TPO and TSH-R molecules and support the concept that immunodominant T cell epitopes are located on amino acid residues 100-119 and 625-644 of TPO in HT and amino acid residues 158-176, 207-222 and 343-362/357-376 of TSH-R in GD. Our studies also demonstrate that thyroid-specific T cells can be classified into Th0, Th1, and Th2 subsets. TPO- or Tg-specific clones with Th1 phenotype appear to be involved in the pathogenesis of HT, mediating thyroid tissue destruction, whereas TSH-R clones with Th0 phenotype may induce thyroid-stimulating autoantibodies in GD.

Autoantigens↗

PubMed2001

Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma.

Clinical recurrences of differentiated thyroid carcinoma occur in 20% of patients after thyroid surgery. We performed a retrospective analysis of a cohort of patients undergoing routine follow-up testing to detect recurrent thyroid carcinoma over a 2-yr period. One group was prepared for testing by thyroid hormone withdrawal (THW), and the other group remained on thyroid hormone and received injections of recombinant human TSH (rhTSH) before diagnostic whole-body radioiodine scanning (DxWBS). We hypothesized that no differences in the ability to detect residual disease would exist between these 2 groups. Two hundred and eighty-nine patients were examined by both DxWBS and by measurement of the serum thyroglobulin (Tg) response to elevated TSH levels. THW was used for 161 patients, and rhTSH preparation was used for 128 patients. Based on all available testing results, we categorized patients as having metastatic disease, thyroid bed uptake only, or no evidence of disease. We examined the sensitivity, specificity, positive and negative predictive values of the DxWBS, and the stimulated Tg after preparation by THW or rhTSH. Patients with thyroid bed were not considered in accuracy testing. The sensitivity and specificity of the 2 tests were comparable between groups. No significant differences were present in the positive or negative predictive values between groups. The highest negative predictive value (97%) was in patients who had both a negative DxWBS and low stimulated Tg levels after rhTSH. In summary, we were unable to demonstrate a difference in the diagnostic accuracy of DxWBS and/or Tg between patients prepared by either THW or rhTSH. We conclude that preparing patients by rhTSH is diagnostically equivalent to preparing them by THW.

Adult↗

PubMed2001

Effect of various doses of recombinant human thyrotropin on the thyroid radioactive iodine uptake and serum levels of thyroid hormones and thyroglobulin in normal subjects.

Recombinant human TSH (rhTSH), usually given as 0.9-mg doses im on 2 successive days, increases serum thyroglobulin (Tg) and radioactive iodine uptake (RAIU) in residual thyroid tissue in patients with thyroid cancer. We previously reported that a single, relatively low dose of rhTSH (0.1 mg im) is a potent stimulator of T(4), T(3), and Tg secretion in normal subjects. The present study describes the effects of higher doses of rhTSH on thyroid hormone and Tg secretion. Six normal subjects for each dose group, having no evidence of thyroid disease, received either 0.3 or 0.9 mg rhTSH by im injection. Serum TSH, T(4), T(3), and Tg concentrations were measured at 2, 4, and 8 h and 1, 2, 3, 4, and 7 days after rhTSH administration. The peak serum TSH concentrations were 82 +/- 18 and 277 +/- 89 mU/L, respectively, for the 0.3- and 0.9-mg doses of rhTSH. Serum T(4), T(3), and Tg concentrations increased significantly in subjects receiving 0.3 and 0.9 mg rhTSH, with significant increases in T(4) and T(3) being observed before significant increases in serum TG: Peak concentrations of serum T(4), T(3), and Tg, after 0.3 mg rhTSH administration, were 100 +/- 19, 131 +/- 14, and 1035 +/- 724% above individual baselines, respectively. Similarly, peak concentrations of serum T(4), T(3), and Tg, after 0.9 mg rhTSH administration, were 102 +/- 16, 134 +/- 7, and 1890 +/- 768% above individual baselines, respectively. These data, compared with previously reported data for the responses to 0.1 mg rhTSH, indicated that 0.1, 0.3, and 0.9 mg rhTSH had similar quantitative stimulatory effects on thyroid hormone and Tg secretion, except that the T(4) response was greater in groups receiving 0.3 and 0.9 mg rhTSH than in the group receiving 0.1 mg rhTSH. We also studied the effect of rhTSH on the thyroid RAIU in the group that received 0.9 mg rhTSH. The 6- and 24-h RAIU values were significantly higher after rhTSH (pre-rhTSH, 6-h value = 12.5 +/- 1.8%; 24 h value = 23 +/- 2.7%; post-rhTSH, 6 h value = 27 +/- 4.8%; 24-h value = 41 +/- 4.2%). The stimulating effects of 0.9 mg rhTSH on the 6- and 24-h RAIUs were similar. rhTSH is a potent stimulator of T(4), T(3), and Tg secretion and the RAIU in normal subjects. Single doses greater than 0.1--0.3 mg do not seem to further enhance thyroid hormone or Tg secretion.

Adult↗

PubMed2001

RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults.

Rearrangements of the RET proto-oncogene may occur in both naturally occurring and radiation-induced papillary thyroid carcinomas. Conflicting results on the frequency and type of RET/PTC rearrangements have been reported in relation to age, radiation exposure, and histological tumor variant. We designed the present study to evaluate in a single laboratory, using the same methodologies, the pattern of RET/PTC activation in thyroid tumors from different groups of patients (exposed or not exposed to radiation, children or adults, with benign or malignant tumors) in relationship to the above mentioned variables. We studied 154 patients with benign nodules (n = 65) or papillary thyroid cancer (n = 89). In the last group, 25 were Belarus children exposed to the post-Chernobyl radioactive fallout, 17 were Italian adults exposed to external radiotherapy for benign diseases, and 47 were Italian subjects (25 children and 22 adults) with no history of radiation exposure. Among patients with benign thyroid nodules, 21 were Belarus subjects (18 children and 3 adults) exposed to the post-Chernobyl radioactive fallout, 8 were Italian adults exposed to external radiation on the head and neck, and 36 were Italian adults with naturally occurring benign nodules. The overall frequency of RET/PTC rearrangements in papillary thyroid cancer was 55%. The highest frequency was found in post-Chernobyl children and was significantly higher (P = 0.02) than that found in Italian children not exposed to radiation, but not significantly higher than that found in adults exposed to external radiation. No difference of RET/PTC rearrangements was found between samples from irradiated (external x-ray) or not irradiated adult patients, as well as between children and adults with naturally occurring, not irradiated, thyroid cancer. When analyzing the type of RET/PTC rearrangement (RET/PTC1 or RET/PTC3), no major difference was apparent. In addition, eight cases with an unknown RET/PTC rearrangement and three cases with the concomitant expression of RET/PTC1 and RET/PTC3 were found. No significant correlation was observed between the frequency and/or the type of RET/PTC rearrangement and clinical-epidemiological features of the patients such as age at diagnosis, age at exposure, histological variant, gender and tumor-node-metastasis (TNM) categories. RET/PTC rearrangements were also found in 52.4% of post-Chernobyl benign nodules, in 37.5% of benign nodules exposed to external radiation and in 13.9% of naturally occurring nodules (P = 0.005, between benign post-Chernobyl nodules and naturally occurring nodules). The relative frequency of RET/PTC1 and RET/PTC3 in rearranged benign tumors showed no major difference. In conclusion, our results indicate that the presence of RET/PTC rearrangements in thyroid tumors is not restricted to the malignant phenotype, is not higher in radiation-induced tumors compared with those naturally occurring, is not different after exposure to radioiodine or external radiation, and is not dependent from young age. Other factors, probably influenced by ethnic or genetic background, may act independently from or in cooperation with radiation, to trigger the DNA damage leading to RET proto-oncogene activation.

Adolescent↗

PubMed2002

Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.

The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.

Carcinoma, Papillary↗

PubMed2002

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies.

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.

Autoantibodies↗

PubMed1990

Dominant negative transcriptional regulation by a mutant thyroid hormone receptor-beta in a family with generalized resistance to thyroid hormone.

An abnormal human thyroid hormone beta-receptor (hTR beta-Mf), which has a glycine to arginine substitution in the hormone-binding domain, has been identified in affected members of one family with generalized resistance to thyroid hormone. To better understand the mechanism by which this mutation produces the observed abnormality, expression vectors for the wild-type and mutant thyroid hormone receptors (TRs) were prepared to test hormone-binding activity and trans-activation function. Nuclear extracts of COS-7 cells transfected with wild-type TRs showed specific T3-binding activity, while mutant receptor-transfected COS-7 nuclear extract failed to bind T3. On the other hand, in a avidin-biotin complex DNA-binding assay, in vitro translated hTR beta-Mf showed high binding activity to the thyroid hormone response element, which was indistinguishable from that of wild-type TRs. In a transient expression study, only the wild-type TRs activated a rat GH gene promoter-chloramphenicol acetyltransferase fusion gene in a T3-dependent manner. Additionally, when wild-type TR and hTR beta-Mf were cotransfected, hTR beta-Mf inhibited gene activation regulated by wild-type TRs. From these results we conclude that 1) hTR beta-Mf has no demonstrable T3 binding and appears to have minimal, if any, ability to activate a thyroid hormone-responsive gene in spite of its preserved ability to bind to a TRE in DNA; 2) hTR beta-Mf inhibits the transcriptional activation of a thyroid hormone-responsive gene by the wild-type TRs in a dominant manner; and 3) the dominant negative regulatory function of hTR beta-Mf appears to explain the clinical manifestations of thyroid hormone resistance produced by this mutation when present in the heterozygous state.

Animals↗

PubMed2005

Electrical impedance scanning of thyroid nodules before thyroid surgery: a prospective study.

BACKGROUND: Electrical impedance scanning (EIS) is a novel imaging technique based on differential electrical conductivity and capacitance of malignant and normal human tissues. The aim of this study was to evaluate the accuracy of EIS in the detection of thyroid malignancies. METHODS: Patients with thyroid nodules scheduled for thyroid surgery were eligible for the study. Enrolled patients underwent EIS with a T-Scan 2000ED. Nodule location, size, and type (cystic vs. solid) measured by ultrasound, cytology results, thyroid conductivity, and capacitance calculated by EIS were recorded. EIS results were interpreted as positive or negative for malignancy and compared with final histopathology results. Study end points included EIS accuracy, sensitivity, specificity, negative and positive predictive values, and false-positive and false-negative rates. RESULTS: Sixty-four patients were enrolled onto the study, and all underwent either lobectomy-isthmusectomy (20%) or total thyroidectomy (80%). The mean tumor diameter was 2.64 +/- 14.8 mm. Thyroid cancers were identified by histology in 30 patients (46.9%). There were 11 false-positive and four false-negative cases. The overall diagnostic accuracy of EIS was 76.6% (49 of 64 correct diagnoses). The sensitivity and specificity of EIS were 86.7% (26 of 30 true positive) and 67.6% (23 of 34 true negative), respectively. The corresponding positive and negative predictive values were 70.3% and 85.2%. CONCLUSIONS: EIS is a potentially useful imaging modality for differentiating thyroid neoplasms. If these results are confirmed in large-scale trials, EIS may be an important part of the evaluation of thyroid nodules.

Adolescent↗