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PubMedDate not supplied

Anti-thyroid antibodies in Italian scleroderma patients: association of anti-thyroid peroxidase (anti-TPO) antibodies with HLA-DR15.

OBJECTIVE: To evaluate the frequency of anti-thyroid antibodies in a group of patients with scleroderma (SSc) and to analyze their genetic association with the HLA class II antigens. METHODS: Anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) antibodies were measured by hemagglutination techniques. Thyroid function was evaluated by determining the levels of FT3, FT4 and TSH. HLA-DR typing was carried out using a standard complement-dependent microlymphocytotoxicity test. RESULTS: The proportions of patients with anti-TG and anti-TPO antibodies were 12% (10/85) and 19% (16/85) respectively. Two patients with anti-thyroid antibodies had overt hypothyroidism and shared the HLA-DR3 allele. The SSc subjects with anti-TPO antibodies showed a higher frequency of the HLA-DR15 allele than the patients without these antibodies. CONCLUSION: A considerable number of patients with scleroderma have antibodies to thyroid antigens without exhibiting any alterations of their thyroid function. HLA-DR15 is an immunogenic marker for the formation of antibodies against microsomal thyroid peroxidase.

Adult↗
PubMed1989

The aging thyroid. The use of thyroid hormone in older persons.

The overall prevalence of thyroid hormone use in an unselected population of older adults (n = 2575; average age, 68.6 years) was 6.9% (10.0% in women and 2.3% in men). Eighty-one percent of women taking it were doing so for appropriate indications, eg, hypothyroidism, while 12% were not, eg, for obesity or high serum cholesterol; more men (29%) were taking it inappropriately. Inappropriate use was associated with desiccated thyroid more than with thyroxine. After follow-up averaging 6.9 years, 58% of inappropriate users were still taking it. Underuse also occurred. Thirty-seven percent of those definitely hypothyroid had a clearly elevated serum thyrotropin level (greater than 10 mU/L) despite thyroid therapy. Thyroid therapy is common in the elderly; most is appropriate. When inappropriate use occurs, it is more common in men and more often associated with desiccated thyroid, still commonly used in this age group. In chronic users of thyroid hormone, it is important to review currently appropriate indications and to measure serum thyrotropin levels to assess the adequacy of treatment of primary hypothyroidism.

Age Factors↗
PubMed1999

Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors.

Sequence specific-differential display (SS-DD) is a powerful method for screening significant changes in gene expression between normal and malignant tissues. Using this method, we detected 3 genes for which the expression is much decreased in thyroid tumors. After sub-cloning and sequencing analysis, one of the genes was revealed to be acid ceramidase (AC). The expression of AC in normal thyroids and thyroid tumors was examined by semi-quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). Obvious decreases in the expression of AC mRNA were observed in 5/6 follicular adenomas, 2/2 adenomatous goiters, 3/6 papillary carcinomas and 1/2 follicular carcinomas. To confirm this result, real-time quantitative PCR analysis (TaqMan PCR) was carried out. The relative expression level of AC mRNA compared with that of GAPDH mRNA was reduced in follicular adenomas, follicular carcinomas, and papillary carcinomas. Further, the expression of AC mRNA was extremely reduced in 2 anaplastic carcinomas. These results suggest a possible relationship between thyroid tumorigenesis and the expression of AC mRNA. Moreover, the increased expression of AC mRNA in normal thyroid tissues suggests some fundamental roles of AC in thyroid function.

Acid Ceramidase↗
PubMed1997

Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells.

Decreased iodide uptake in de-differentiated thyroid carcinomas impedes radioiodide therapy. RTPCR analysis revealed reduced expression of Na+/I- symporter (NIS) mRNA in human thyroid carcinomas as compared to normal thyroid. However, in follicular thyroid carcinoma cell lines FTC-133 and FTC-238, treatment with 1 microM all-trans retinoic acid (RA) markedly increased NIS mRNA levels. Anaplastic thyroid carcinoma cell lines HTh74 and C643 showed basal expression of NIS mRNA, but no RA-stimulation. All four cell lines contained the approximately 80 kD NIS protein as judged by Western blot, although they did not accumulate iodide. In contrast, in nontransformed rat FRTL-5 cells, 1 microM RA downregulated NIS mRNA levels, inhibited the TSH- or forskolin-triggered induction of NIS message after TSH-depletion, and reduced iodide uptake to 38% after 5 d. This divergent RA-responsivity of NIS may provide the means to target radioiodide to thyroid carcinomas by upregulating iodide transport into tumor tissue while simultaneously inhibiting iodide accumulation in normal thyrocytes and may thus re-establish the potential for radioiodide therapy.

Animals↗
PubMed1993

Pathogenesis of thyroid-associated ophthalmopathy: an autoimmune disorder of the eye muscle associated with Graves' hyperthyroidism and Hashimoto's thyroiditis.

Thyroid-associated ophthalmopathy, the progressive eye disorder which occurs frequently in patients with Graves' hyperthyroidism and, occasionally, in those with Hashimoto's thyroiditis, may be a two-stage disorder of the eye muscle. In the first stage, which may occur in the great majority of patients with Graves' hyperthyroidism and in an unknown, but probably small, proportion of those with Hashimoto's thyroiditis, antibodies and CD4+ (helper) T lymphocytes reactive with eye muscle and thyroid shared antigens, of which 64-kDa membrane proteins are good candidates, may initiate a mild eye muscle inflammation, manifested as eye muscle swelling on orbital imaging. The second stage, which occurs in about 25% of patients with Graves' hyperthyroidism and in 2% of those with Hashimoto's thyroiditis, may be due to reactivity of cytotoxic antibodies against eye muscle-specific membrane antigens, one of which at approximately 35 kDa appears a likely candidate, and, possibly, cytotoxic T cells in the context of the appropriate class I MHC molecule. Orbital connective tissue inflammation, which plays an important role in the development of progressive orbital inflammation, is likely to be secondary to the eye muscle reaction. The recent cloning of a 64-kDa thyroid and eye muscle antigen which shares significant homology with the muscle protein tropomodulin and mapping of its antibody-reactive epitopes provide structural information about one candidate eye muscle autoantigen and promise for a more rational approach to the diagnosis and management of this common, progressive eye disorder.

Graves Disease↗
PubMed1990

Growth regulation of normal thyroids and thyroid tumors in man.

Our studies using thyrocyte membranes from different human thyroid tissues, monolayer cultures of human thyrocytes, and the permanant cell line FTC-133 demonstrate the stimulatory effect of TSH on metabolism, DNA synthesis, and cell growth in human thyrocytes. Up- and down-regulation of cAMP cell content fails to show direct effects on DNA synthesis and cell growth in primary thyrocyte cultures in man. Increased AC responsiveness to TSH in adenomatous human thyroid tissues, when compared to normal thyroids of the same patient (p less than 0.005), is thus of only questionable importance for thyroid tumor growth. The permanant cell line FTC-133 was established from differentiated follicular human thyroid cancer cells. FTC-133 cells proved to be of particular usefulness in assessing growth regulation of human thyroid tissue. These cells could be propagated in serum free medium, showed thyroglobulin immunoreactivity and EGF receptors, lacked any fibroblast contamination, and responded to TSH and local active growth factors such as EGF and IGF with a stimulated [3H]thymidine incorporation. The latter could be shown in primary cell cultures of normal and pathological human thyrocytes as well. Additional to the stimulatory effect of TSH and IGF on [3H]thymidine incorporation, these substances show an additive effect when incubated simultaneously. Locally active growth factors and endocrine growth stimulation by TSH therefore act synergistically on thyrocyte growth in human thyrocyte cultures. Whether the TSH effect on cell growth is related to its stimulation of AC remains as yet questionable.

Adenylyl Cyclases↗
PubMed1995

Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma.

For the analysis of cellular proliferative activity and cell death in thyroid diseases, the Ki-67 labeling index, bcl-2 protein expression and cell death of follicular epithelia by immunohistochemistry and in situ DNA nick-end labeling methods were evaluated in normal thyroid tissues as well as in surgical specimens from cases of Hashimoto's disease (16 cases), focal lymphocytic thyroiditis (13 cases), Graves' disease (15 cases), follicular adenoma (20 cases) and papillary carcinoma (43 cases). Cellular proliferative activity and cell death were both enhanced in cases of thyroiditis, including Hashimoto's disease and focal lymphocytic thyroiditis. Thyroids from patients with follicular adenoma and papillary carcinoma also showed increased cellular proliferative activity and cell death. In addition, predominant high cellularity and partial loss of bcl-2 protein expression in papillary carcinoma suggested that the overgrowth and dedifferentiation were associated with malignancy.

Carcinoma, Papillary↗
PubMed1994

Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct.

The clinical evaluation of thyroid imaging with 99mTc, 201Tl, and 67Ga in the uncommon, but potentially serious, disorder of acute suppurative thyroiditis (AST) with abscess formation due to infection from a persistent thyroglossal duct is reported. The 99mTc image showed functioning areas of the diseased thyroid gland and the 201Tl image demonstrated abscess formation in the thyroid gland of this patient. In addition, marked 67Ga accumulation was demonstrated in a wide area covering not only the area of the thyroid gland involved, but also associated circumferential inflammatory lesions in a patient with AST. The net thyroid uptake of 67Ga at 72 hours was calculated to be 13.8% of the injected dose.

Abscess↗
PubMed1999

Cold thyroid nodule as the sole manifestation of Rosai-Dorfman disease with mild lymphadenopathy, coexisting with chronic autoimmune thyroiditis.

A case of thyroid Rosai-Dorfman disease (RDD) without apparent lymphadenopathy in a 49-year-old woman with underlying euthyroid chronic autoimmune thyroiditis, as indicated by high thyroid autoantibodies titers, is presented. The initial presentation was that of a cold, hypoechogenic nodule of left thyroid lobe which increased in size during the two years of follow up, together with new ultrasonographic findings of the right lobe. No biochemical abnormalities were found apart from mild hypercalcemia. A near total thyroidectomy was performed. Histologically, the left lobe nodule as well as the right lobe lesions consisted of typical RDD cellular population, with the pathognomonic phenomenon of emperipolesis. Infiltration to the periphery of the gland was observed and three adjacent lymph nodes were also involved. The uninvolved thyroid parenchyma showed changes compatible with chronic autoimmune thyroiditis. No other localizations or systemic manifestations of RDD were revealed. Normocalcemia was restored promptly and the patient remains free of clinically overt disease one year post-operatively.

Aged↗
PubMed2005

Thyroid hemiagenesis and incidentally discovered papillary thyroid cancer: case report and review of the literature.

Thyroid hemiagenesis (TH) is a rare congenital abnormality in which one thyroid lobe fails to develop. Its prevalence is uncertain, because the absence of one thyroid lobe does not usually cause clinical symptoms. The detection of TH is usually incidental when the evaluation of other thyroid disorders is requested. It is more frequently found in female than in male patients (3:1 ratio) and in the left lobe compared to the right lobe. We report the case of a 54-yr-old man, presenting with a large multinodular right-sided goiter, with mediastinal extension and dysphagia. Thyroid scan and ultrasound study showed the absence of the left lobe. The patient underwent surgery for compressive symptoms, and the operation confirmed the absence of the left lobe. Histological examination demonstrated a multi-nodular goiter with papillary carcinoma. To our knowledge, this case represents the first reported case of association between TH and papillary thyroid carcinoma in a male patient, and the second in which the tumor arose in the right lobe.

Carcinoma, Papillary↗
PubMed1986

Effects of thyrotropin and thyroid stimulating immunoglobulins on gangliosides labelling of human thyroid cultured pathological cells.

Gangliosides are known to play an important role in different cell processes. We have investigated the effect of TSH on [14C] glucosamine incorporation into gangliosides of cultured pathological cells isolated from colloid nodular goiter, follicular adenoma, and toxic adenoma. The effect of thyroid stimulating immunoglobulins (TSI) has also been similarly studied on primary cultures from colloid nodular goiter and from porcine thyroid cells. Immunoglobulins were purified from sera of Graves' disease patients. Cells were cultured with or without either stimulator and labelled with [14C] glucosamine during 24 h. Total lipid extracts were fractionated on DEAE Sephadex A 25. Eluted gangliosides were analysed by thin layer chromatography, detected by autoradiography and scraped off for radioactivity measurement. Radioactivity was related to the free cholesterol content. The ganglioside pattern of human thyroid cells in primary cultures is found to vary and to closely reflect the ganglioside pattern of the corresponding gland. No ganglioside pattern could be related to a specific thyroid disorder. When cells are treated with TSH, the amount of [14C] glucosamine incorporated in total gangliosides varies according to diseases. The radioactivity incorporated in gangliosides from colloid nodular goiter cells is not similarly affected by TSH and TSI. In porcine thyroid cells, TSH and TSI have the same effect on glucosamine incorporation into gangliosides. Thus it appears that TSH and TSI may differently affect the gangliosides labelling according to the origin of the thyroid cells.

Animals↗
PubMed1991

Measurement of thyroid hormone in the rat thyroid gland by radioimmunoassay.

The present paper describes (i) a hydrolysis technique with Pronase and leucine aminopeptidase using one rat thyroid gland, resulting in maximum release of thyroid hormones and minimum deiodination, and (ii) a simple and rapid procedure for thyroid hormone radioimmunoassays in thyroid hydrolysates using commercial kits intended for serum thyroid hormone determinations. The procedure is used to determine T4, T3, and rT3 concentrations and hormonal molar ratios in a thyroid gland from a male Wistar rat. The reliability of the method is also studied.

Animals↗
PubMed1979

Thyroid peroxidase activity in euthyroid and mild hypothyroid patients with Hashimoto's thyroiditis.

Thyroid peroxidase (TPO) activity was measured spectrophotometrically according to Hosoya's guaiacol method. The mean TPO activity in ten patients with Hashimoto's thyroiditis was 19.8 +/- 7.6 (mean +/- SE) in an arbitrary unit, which was not significantly different from the normal value in seven normal thyroid tissues (33.7 +/- 5.4). The ten patients were divided into two groups, euthyroid and mild hypothyroid, on the basis of their basal serum TSH. In the euthyroid group, TPO activity (8.17 +/- 1.3) was significantly less than the normal tissue (p less than 0.01). In the hypothyroid group, TPO activity (27.64 +/- 13.8) was almost similar to the normal tissue. A positive correlation was obtained between TPO activity and serum TSH in ten patients with Hashimoto's thyroiditis (r = 0.85, p less than 0.01). It was concluded that TPO activity is significantly decreased in Hashimoto's thyroiditis even when the thyroid function was still within normal range, but the activity might be restored to normal in hypothyroid patients by the stimulation of elevated TSH.

Adult↗
PubMed1986

Thyroid gland volume and thyroid function during and after acute hepatitis infection.

Thyroid function, the occurrence of goiter, and ultrasonically determined thyroid gland volume were investigated in 23 consecutive nonalcoholic patients with acute viral hepatitis during and six months after recovery, and compared with data obtained from 23 matched controls. Seven patients had clinically detectable goiter during disease, but only one after recovery (P less than 0.05). Median thyroid volume was 28 mL (range 15 to 42 mL) compared with 18 mL (range 12 to 27 mL) after recovery (P less than 0.001), and 17 mL (range 11 to 24 mL) in the controls (P less than 0.001). During acute hepatitis, serum levels of thyroxine, thyroxine binding globulin, and free thyroxine index were significantly increased while triiodothyronine and thyrotropin levels were unaltered and triiodothyronine resin uptake and free triiodothyronine index levels were decreased. After recovery all thyroid variables were normalized. In conclusion, acute liver disease was associated with a marked increase in thyroid volume, but the study did not clarify the mechanism underlying thyroid enlargement.

Acute Disease↗
PubMed1984

Influence of thyroid autoantibodies on thyroid cellular growth in vitro.

Porcine thyroid follicle cells, cultured in suspension, were employed to investigate the effects of immunoglobulin preparations from patients with colloid goitre, Graves' disease or Hashimoto's thyroiditis on thyroid growth in vitro. Epidermal growth factor (EGF, 19 ng/ml) was used as a reference for maximum growth stimulation and produced a 9-fold increase in [3H]thymidine incorporation. Immunoglobulins (1000 micrograms/ml) were found to increase [3H]thymidine incorporation compared to control: from 10 normal individuals 32 +/- 4% (mean +/- SEM, % of EGF response), from 10 patients with colloid goitre 26 +/- 4% (not significantly different from normal), from 10 patients with Graves' disease 19 +/- 3% (P less than 0.05) and from 15 patients with Hashimoto's thyroiditis 11 +/- 2% (P less than 0.001). No patient immunoglobulin preparation showed activity greater than that of normal individuals. The lower growth stimulatory activity in Graves' disease and Hashimoto's thyroiditis remained after heat inactivation of serum and is thought to reflect surface binding of thyroid autoantibodies.

Animals↗
PubMed1995

Modulation of thyroid hormone action by mutant thyroid hormone receptors, c-erbA alpha 2 and peroxisome proliferator-activated receptor: evidence for different mechanisms of inhibition.

Thyroid hormone action is not only determined by hormone availability, but also by target organ sensitivity. A dominant negative interaction is known to occur between thyroid hormone receptors (TRs) and the non-ligand binding splicing variant c-erbA alpha 2 as well as mutant TR beta 1 from kindreds with resistance to thyroid hormone. We compared the inhibitory effect of naturally occurring mutant hTR beta 1, artificially created hTR alpha 1 mutants, c-erbA alpha 2 and the human peroxisome proliferator-activated receptor (hPPAR) on three prototypic T3-response elements (TREs), TRE-PAL, DR + 4 and TRE-LAP. The inhibitory effect of mutant hTR alpha 1 and beta 1 occurred only on TRE-LAP and to a minor degree on DR + 4 when equimolar ratios of mutant/wildtype receptor were present. In contrast, the c-erbA alpha 2 splicing variant and the hPPAR inhibited TR action on all three TREs. Gel mobility shift experiments in the presence of T3 showed increased binding of mutant hTR alpha 1 and beta 1 only to TRE-LAP compared to the binding of wildtype hTRs, thereby explaining their TRE-selective dominant negative potency. Contrarily, equal amounts of c-erbA alpha 2 or hPPAR protein did not bind to either of the three response elements even in the presence of RXR. Since the TR:RXR heterodimers were only partially displaced from DNA in the presence of excess amounts of c-erbA alpha 2, it is likely that the TRE-unspecific dominant negative action of c-erbA alpha 2 is due in part to competition for DNA-binding and for TR-auxiliary proteins. In contrast, equimolar amounts of hPPAR completely inhibited the DNA-binding of hTR beta 1:RXR heterodimers, but not of TR:TR homodimers, suggesting that hPPAR has a higher RXR-binding affinity and is therefore a potent competitor for intranuclear RXR. Since thyroid hormones and peroxisome proliferators regulate in part a similar subset of target genes involved in fatty acid metabolism, these results suggest the possibility of cross-talk among the thyroid hormone and peroxisome proliferator signalling pathways. In summary, the results suggest that thyroid hormone action can be modulated by at least three different mechanisms: (i) increased binding of mutant hTRs to specific TREs; (ii) efficient competition for limiting amounts of RXR through the preferential formation of hPPAR:RXR, rather than TR:RXR heterodimers; and (iii) competition for binding to DNA and to auxiliary proteins other than RXR in the case of c-erbA alpha 2.

DNA↗
PubMed1987

Thyroid function and thyrotropin levels in rabbits immunized to produce antibodies against thyroid hormones.

Various parameters of thyroid function were studied in 27 rabbits, out of which 10 were immunized to produce antibodies against triiodothyronine (T3), 9 against thyroxine (T4) and 8 were normals. Estimations of T3, T4, Free T4 (FT4) and thyrotropin (TSH) in blood, qualitative and quantitative analysis of iodoamino acids in serum, protein bound iodine-131 (PB131I), butanol extractable iodine-125 (BE125I) and measurement of the disappearance rates of 125I-labelled T3 and T4 from plasma were done. In addition, glandular changes were also studied by measurement of 131I uptake, thyroid scanning and chromatographic analysis of hydrolysate of soluble iodoproteins. In T3 immunized animals, levels of T3 in serum increased by 38 to 125 times, levels of TSH also showed a significant rise (7.4 +/- 1.2 vs 28 +/- 9 ng/mL). Chromatographic analysis of iodoamino acids in serum as well as in the hydrolysate of the thyroid gland demonstrated a selective increase in synthesis of T3. Rate of disappearance of T3 from blood showed a significant decline. Thyroid glands in the immunized rabbits showed signs of hypertrophy and hyperplasia. Identical studies done in rabbits immunized to produce antibodies against T4 showed a similar pattern though of variable degree. Our studies indicate that the thyroid glands of the immunized rabbits undergo marked alterations resulting in selective increase in the synthesis and secretion of the particular thyroid hormone against which they were immunized. They do so under the influence of increased levels of TSH.

Amino Acids↗
PubMed1995

Prevalence of thyroid antibodies among healthy middle-aged women. Findings from the thyroid study in healthy women.

Autoimmune thyroiditis is the most common cause of subclinical hypothyroidism in North America, is more common in women than men, and is a risk factor for the development of coronary heart disease (CHD). We measured thyroid-stimulating hormone (TSH) and two thyroid antibodies, thyroid peroxidase and thyroglobulin, in stored sera of the participants (aged 44 to 54 years) of the Healthy Women Study. We selected 254 samples from the premenopausal baseline examination in 1983 to 1985 and from a follow-up examination that occurred an average of 5.7 years later (range, 3 to 7.7 years). At follow-up, 95 women remained premenopausal, 98 had ceased menstruating for at least 12 months, and 61 were taking postmenopausal hormone therapy. Overall, the prevalence of the thyroid antibodies in this healthy population was high at both time points (21 to 26%). Women with antibodies had higher TSH concentrations than did those with no antibodies (2.68 +/- 1.3 versus 1.51 +/- .73 mU/L, P < 0.001); this relationship was statistically significant even after excluding those with subclinical hypothyroidism (TSH > 6.0 mU/L). TSH and antibody levels did not differ by menopausal status or hormone therapy use at follow-up. Given the high prevalence of thyroid antibodies among healthy middle-aged women, long-term follow-up is warranted to ascertain whether the presence of antibodies is associated with subsequent excess risk of disease, in particular, CHD.

Adult↗