Search PubMed⌕ Search

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.

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

At least 253 records · Page 14Linked to original sources
PubMed1995

Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules.

OBJECTIVE: The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied in patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels. PATIENTS: A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied. MEASUREMENTS: In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery. RESULTS: All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive in the former patient but also in the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative in the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC. CONCLUSIONS: This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels.

Adolescent↗
PubMed1996

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome.

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.

Adult↗
PubMed1990

Thyroid size determined by ultrasound. Influence of physiological factors and non-thyroidal disease.

Grading of goitre size according to WHO or the palpatory estimation of thyroid volume does not allow a quantitative estimation of thyroid size or an objective follow-up during treatment with e.g. radioiodine. The present and other studies have demonstrated that the ultrasonic evaluation of thyroid volume is both accurate and precise. In addition, it is non-invasive, rapid, inexpensive and without discomfort to the patient. Using this technique it was demonstrated that thyroid volume increases with increasing age and body weight in both sexes, with weight having the most pronounced influence. The relationship between thyroid volume, body weight and age in non-goitrous healthy subjects can be described using a formula that allows the calculation of normal thyroid size for a population: Thyroid volume (ml) = 1.97 + 0.21 x bodyweight (kg) + 0.06 x age (years). Cigarette smoking is associated with an approximately 10-fold increase in goitre frequency probably due to a combination of an increased sympathetic stimulation of the thyroid and an iodine deficiency state caused by inhalation of thiocyanate. Although no seasonal alteration in serum TSH level could be demonstrated thyroid volume is 23% higher in the winter than in the summer. Cyclic alterations of thyroid volume possibly related to TSH alterations have been found with a 50% difference between minimum values in the first half and maximum values in the second half of the menstrual cycle. Nonthyroidal illnesses are associated with marked alterations in thyroid volume. Thus, chronic renal disease and acute hepatic disease demonstrate significant increases in thyroid volume although the precise mechanisms have not been clarified. Chronic hepatic disease per se and chronic nonrenal nonhepatic disease does not seem to influence thyroid volume. Chronic alcoholism, however, with or without liver cirrhosis is associated with a marked decrease in thyroid volume and an increase in the amount of fibrosis probably related to a direct toxic effect of alcohol on the thyroid. All these factors should be kept in mind when goitre frequency, goitrogenic action of drugs and goitre treatment effects are evaluated.

Age Factors↗
PubMed1987

The incidence of thyroid carcinoma in Hashimoto's thyroiditis.

The incidence of thyroid carcinoma in Hashimoto's thyroiditis has been a widely debated issue. Previous authors have reported on this topic by analyzing series of patients with Hashimoto's thyroiditis or patients with thyroid carcinoma, but not both of those populations in the same series. The population consists of a consecutive series of 800 patients operated on for thyroid nodules not associated with a radiation history. Among 161 patients with the diagnosis of thyroid carcinoma, 61 (38%) had coexistent Hashimoto's thyroiditis. In comparison, among 161 sex- and age-matched patients with colloid nodules in the same population, 18 (11%) had Hashimoto's thyroiditis. Furthermore, in the series as a whole, the incidence of Hashimoto's thyroiditis in 423 patients with colloid nodules was 10 per cent. From the perspective of the Hashimoto's thyroiditis population in the same series of 800 thyroidectomies, among 267 patients with Hashimoto's thyroiditis 61 (23%) had coexistent carcinoma. In comparison, among 267 age- and sex-matched patients with colloid nodules there were only ten coexistent carcinomas for an incidence of 4 per cent. The high incidence of carcinoma of the thyroid in Hashimoto's thyroiditis lends credence to the hypothesis that Hashimoto's thyroiditis is a predisposing factor in the development of thyroid carcinoma.

Adolescent↗
PubMed2006

Comparison of the biological activity of recombinant human thyroid-stimulating hormone with bovine thyroid-stimulating hormone and evaluation of recombinant human thyroid-stimulating hormone in healthy dogs of different breeds.

OBJECTIVE: To evaluate whether use of recombinant human (rh) thyroid-stimulating hormone (TSH) induces equivalent stimulation, compared with bovine TSH (bTSH), and to evaluate activity of rhTSH in dogs of various large breeds. ANIMALS: 18 healthy research Beagles and 20 healthy client-owned dogs of various breeds with body weight > 20 kg. PROCEDURES: The 18 Beagles were randomly assigned to 3 groups, and each dog received either 75 microg of rhTSH, IM or IV, or 1 unit of bTSH, IM, respectively, in a crossover design. The 20 client-owned dogs received 75 microg of rhTSH, IV. Blood samples were taken before and 6 hours after TSH administration for determination of total serum thyroxine (T(4)) concentration. Additional blood samples were taken after 2 and 4 hours in Beagles that received rhTSH, IM. RESULTS: There was a significant increase in T(4) concentration in all dogs, but there were no differences between values obtained after administration of bTSH versus rhTSH or IV versus IM administration of rhTSH. Although there was a significant difference in age and body weight between Beagles and non-Beagles, there was no difference in post-TSH simulation T(4) concentration between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated an equivalent biological activity of rhTSH, compared with bTSH. Use of 75 microg of rhTSH, IV, did not induce a different magnitude of stimulation in large-breed dogs, compared with Beagles. Euthyroidism was confirmed if post-TSH simulation T(4) concentration was > or = 2.5 microg/dL and at least 1.5 times basal T(4) concentration.

Animals↗
PubMed1989

Negative regulation of the thyroid-stimulating hormone alpha gene by thyroid hormone: receptor interaction adjacent to the TATA box.

Thyroid-stimulating hormone alpha and beta subunit genes are negatively regulated by thyroid hormone at the transcriptional level. Transient gene expression studies were used to demonstrate that the erbA beta form of the thyroid hormone receptor mediates negative regulation of the alpha-subunit promoter in a hormone-dependent manner. In JEG-3 choriocarcinoma cells, which are deficient in thyroid hormone receptors, coexpression of erbA beta with alpha CAT reporter genes markedly suppressed alpha CAT expression after treatment with thyroid hormone, whereas a reporter gene containing a known positive thyroid response element was induced. Thus, a single form of thyroid hormone receptor mediates both positive and negative responses to thyroid hormone in this system. Transient expression analyses of alpha gene 5' flanking sequence deletion mutants localized the negative thyroid response element to the proximal region of the promoter between -100 and +4 base pairs. The location of the negative thyroid response element in the alpha gene is therefore distinct from that of previously identified regulatory elements including the tissue-specific upstream regulatory elements, the cAMP response elements, and the glucocorticoid response elements. Overlapping segments of the alpha promoter were examined for potential thyroid hormone receptor binding sites by using gel shift assays and biotinylated DNA-binding studies. A specific thyroid hormone receptor binding site was identified between -22 and -7 base pairs, which is immediately downstream from the TATA box. This region of the alpha promoter interacts with erbA beta receptor synthesized in vitro as well as with endogenous nuclear thyroid hormone receptors, and it competes for receptor binding to a known positive thyroid response element. These studies suggest a mechanism for negative regulation in which the thyroid hormone receptor interacts with the alpha gene promoter immediately downstream of the TATA box to inhibit transcription.

Base Sequence↗
PubMed1990

Experimental murine thyroiditis induced by porcine thyroid peroxidase and its transfer by the antigen-specific T cell line.

Thyroid peroxidase purified from porcine thyroid (pTPO) was found to induce an experimental murine thyroiditis with genetic restriction which was very different from that induced by mouse thyroglobulin (mTg). C57BL/6 and C57BL/10 (both H-2b) were good responders for thyroiditis, whereas A/J (H-2a), BALB/c (H-2d), DBA/2 (H-2d), CBA (H-2k), C3H/He (H-2k), and SJL/J (H-2s) were poor responders. Genetic analyses using congenic or recombinant strains revealed the following results: The H-2-linked gene (probably the I-A subregion) had a weak association with the induction of thyroiditis, and at least one non-H-2-linked gene controlled the development of thyroid lesions; antibody production to pTPO, porcine thyroglobulin (pTg) and mTg did not correlate with the incidence of thyroiditis in any strain. None of the murine thyroid microsome-specific antibodies tested by the indirect immunofluorescent technique was detected. The T cell line specific for pTPO was successfully transferred to produce thyroid lesions in C57BL/6 mice. Thyroiditis appeared 3 days after the transfer of T cell blasts, and a low concentration of anti-pTPO antibodies was detected concurrently. Thyroid lesions remained up to 48 days with almost the same extent of thyroiditis, but anti-pTPO antibodies gradually increased. In the vaccination experiments using either 0.645 C/kg (2500 rad)-irradiated or 0.3% glutaraldehyde-fixed T cell blasts, the induction of thyroid lesions by transfer was strongly suppressed. Glutaraldehyde fixation was more effective than X-irradiation in preventing thyroiditis after the transfer of T cell blasts. Vaccination also suppressed significantly the development of thyroid lesions after pTPO administration.

Animals↗
PubMed1992

Thyroid peroxidase antibodies in children with autoimmune thyroiditis.

AIMS: To compare the prevalence of thyroid peroxidase antibodies in 25 children with autoimmune thyroid disorders and in 41 children and young adults with type 1 diabetes, and to test the prevalence of thyrotropin receptor antibodies. METHODS: Two commercially available radioimmunoassays for antibodies to thyroid peroxidase, a commercially available agglutination test of particles coated with thyroid microsomal antigens, and a radioimmunoassay for thyrotropin receptor antibodies were used. Patients and controls were studied. RESULTS: One of the radioimmunoassays detected thyroid peroxidase antibodies not only in all children with autoimmune thyroid disorders and children and young adults with type 1 diabetes and thyroid microsomal antibodies, but also in 20% of healthy control children without microsomal antibodies. With this thyroid peroxidase assay and with microsomal agglutination, 94% of the children with autoimmune thyroiditis, 71% of those with Graves' disease, and over 90% of those with type 1 diabetes and thyroid dysfunction tested positive. In the other radioimmunoassay for thyroid peroxidase antibodies thyroid peroxidase antibody titres in half or more of the children with microsomal antibodies failed to reach the level of positivity given by the producers. Eighty five percent of children with Graves' disease and 71% of those with autoimmune thyroiditis had thyrotropin receptor antibodies but so did 35% of children studied for other endocrinological disorders such as delayed growth or puberty. CONCLUSIONS: Testing patients with well characterised disorders of thyroid function and with other endocrine disorders is important in evaluating the efficacy of new diagnostic tests for thyroid autoantibodies.

Adolescent↗
PubMed1998

Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response.

Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.

Animals↗
PubMed1995

Sonographic demonstration of a normal thyroid gland excludes ectopic thyroid in patients with thyroglossal duct cyst.

OBJECTIVE: Preoperative thyroid scintigraphy has been performed in patients with presumed thyroglossal duct cyst to document a normal thyroid and to exclude the possibility of an ectopic thyroid mimicking a thyroglossal duct cyst. Often, an ectopic thyroid is the patient's only functioning thyroid tissue, and its removal will result in hypothyroidism. The purpose of this study was to determine whether demonstration of a normal thyroid gland by sonography in children with thyroglossal duct cyst can exclude ectopic thyroid and thereby obviate routine preoperative thyroid scintigraphy. MATERIALS AND METHODS: We studied 30 patients with pathologically proved thyroglossal duct cysts who had neck sonograms. The sonograms were evaluated for the presence or absence of a normal thyroid gland. The medical records of these children were also reviewed. Three children had normal preoperative radionuclide thyroid scans. All the children were clinically euthyroid preoperatively. Follow-up was available in 15 of the 30 patients, and all of these patients were clinically euthyroid postoperatively. RESULTS: A sonographically normal thyroid gland was detected in all patients. CONCLUSION: Preoperative sonographic identification of a normal thyroid gland in patients with thyroglossal duct cyst confirms a source of thyroid hormone separate from the thyroglossal duct cyst and thus excludes ectopic thyroid. Routine thyroid scintigraphy is not necessary.

Child↗
PubMed1994

Effects of interleukins on EGF-stimulated growth promotion in human thyroid cells: differential modifications by IL-2 and IL-6 in Graves' and normal thyroid cells.

To investigate the role of interleukins on the growth of human thyroid cells, the effect of IL-2, IL-4 and IL-6 was studied on EGF-induced [3H]-thymidine uptake, cell cycle by flow cytometry, and mRNA levels of cellular proto-oncogene c-fos in thyroid monolayer cells from eighteen patients with Graves' disease and sixteen with non-thyroidal disease. EGF stimulated the DNA synthesis and the expression of c-fos mRNA both in Graves' thyroid cells and in normal thyroid cells. A dose-dependent inhibition of Graves' thyroid cell growth was observed with increasing concentration of IL-2 regardless of coculture with EGF. IL-2 did not influence [3H]-thymidine uptake nor the percentage of S+G2/M phase in cell cycle in normal thyroid cells. Such effects were not modified by the elimination or addition of lymphocytes. IL-2 did not affect the EGF-induced expression of c-fos mRNA in both Graves' and normal thyroid cells. IL-6 (10(-2)-10 ng/ml) stimulated the [3H]-thymidine uptake up to 218-303 % of control level, and the percentage of cells in S+G2/M phase was increased in IL-6-treated normal thyroid cells as compared to EGF-treated cells. IL-6 did not augment these parameters in Graves' thyroid cells. When EGF was included with IL-6, the level in c-fos mRNA was further augmented in normal thyroid cells. Such an additive effect was not seen in Graves' thyroid cells. Incubation of Graves' or normal thyroid cells with IL-4 did not affect the [3H]-thymidine uptake nor the percentage of S+G2/M. These data suggest that, compared with normal cells, the growth factors (such as cytokines), may act in an opposite way in Graves' thyroid cells. The different behavior between Graves' and normal thyroid cells in response to IL-2 and IL-6 might contribute to the pathogenesis of goiter formation.

Cell Cycle↗
PubMed2005

Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family.

The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T3 to 17% of that of the normal TRbeta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered.

Adolescent↗
PubMed1984

Thyroid hormone secretion is more sensitive than thyroid cyclic AMP accumulation to stimulation with LATS in mice in vitro and in vivo.

The effects of LATS-immunoglobulin G (IgG) on thyroid hormone secretion and on thyroid cAMP concentrations were investigated in mice and compared to those of TSH. In the in vitro experiments, thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer with LATS-IgG or TSH for 3 h or 2 h and T3 concentrations in buffer and thyroid cAMP were measured by RIA. T3 in the buffer was increased with 1.5 mg/ml of LATS-IgG (A) or 2.5 mg/ml of LATS-IgG (B) (1000%/5 mg or 400%/5 mg in the McKenzie bioassay, respectively), whereas thyroid cAMP was elevated only after incubation with two to four times higher doses of LATS-IgG (A) or LATS-IgG (B). 0.03 mU/ml of TSH increased T3 concentrations, while a two fold higher dose of TSH was required to increase thyroid cAMP. In the in vivo study, 5 mg of LATS-IgG (A) injected intravenously increased serum T4 concentrations but not thyroid cAMP. 2 mU of TSH increased serum T4, while 10 mU was needed to elevate thyroid cAMP. These results indicate that: i) thyroid hormone secretion is more sensitive than increases of thyroid cAMP to stimulation with LATS, which is similar to stimulation with TSH and that: ii) thyroid hormone secretion rather than increases of thyroid cAMP should be employed to detect serum thyroid stimulating activities when mouse thyroids are used.

Animals↗
PubMed1996

TSH-receptor expression and human thyroid disease: relation to clinical, endocrine, and molecular thyroid parameters.

Thyrotropin receptor (TSH-R) gene expression can be positively or negatively regulated by TSH and stimulating TSH-R antibodies (TSAbs) in immortalized thyroid cell lines such as rat FRTL-5 cells. However, regulation is less clear in other mammalian cells including cultures of human thyroid cells. Additionally, it has been suggested, based on FRTL-5 cell data, that TSH-R gene negative regulation by TSH or TSAbs might be lost in Graves' disease. The present study evaluated TSH-R gene transcript levels in thyroids from patients with Graves' disease to correlate in vivo data with in vitro observations or hypotheses. TSH-R mRNA levels were characterized in a total of 66 human thyroid glands with particular concern to levels in Graves' patients. Results were related to clinical parameters, transcript levels of thyroglobulin (TG), and thyroid peroxidase (TPO), as well as transcript levels of thyroid transcription factor 1 (TTF-1) which regulates the expression of all three genes and paired box-gene 8 (Pax-8) which regulates TG and TPO gene expression. Northern blot analyses showed that TSH-R expression was significantly increased, 2.2-fold, in Graves' thyroids (p = 0.0098, n = 35) by comparison to normals (n = 6). TSH-R mRNA levels were decreased to 30% and 7% of normal levels in Hashimoto's thyroids (p = 0.0281, n = 5) and anaplastic carcinomas (p = 0.0033, n = 6), respectively. No significant changes were seen in endemic goiters (n = 8) and in thyroid autonomy (n = 6). TSH-R RNA levels were higher, 3.6-fold, in thyroids of a subgroup of Graves' patients that had not been pretreated with iodide before surgery (n = 10) by comparison to thyroids from those that had been treated before surgery, 1.7-fold (n = 25). TSH-R antibodies exhibited a nonsignificant tendency toward a negative correlation. All other clinical or endocrine parameters showed no clear relation to TSH-R mRNA levels. Pax-8 and TTF-1 transcripts were detectable in normal thyroids; however, Pax-8 expression was increased in Graves' thyroids (3.8-fold), whereas TTF-1 expression was only minimally changed in all thyroids investigated. Changes of the two did not correlate. Pax-8 expression correlated with TG and TPO expression (in all cases, p = 0.0001); TTF-1, despite its minimal change, still correlated with TG (p = 0.0471) but not with TPO expression (p = 0.0984). TTF-1, again despite its minimal changes, correlated positively with TSH-R gene expression (p = 0.0251); however, surprisingly, Pax-8, which does not regulate TSH-R gene expression, correlated even better with TSH-R transcript levels (p = 0.0001). We conclude that augmentation of TSH-R expression levels, and thus potential ligand binding sites, may indicate an important regulatory principle in the pathogenesis of autoimmune hyperthyroidism in vivo: the responsiveness of the TSH-R to TSH and TSAb induced negative regulation is lost. This increase of TSH-R expression levels is not due to an ongoing transcriptional activation of the TTF-1 gene. Pax-8, though positively correlated with TSH-R RNA levels, cannot be the factor either, because Pax-8 does not upregulate TSH-R expression. This predicts that other factors involved in TSH-R induced negative regulation are abnormal and must be searched for and evaluated.

Adolescent↗
PubMed2000

The utility of thyroid nuclear imaging and other studies in the detection and treatment of underlying thyroid abnormalities in patients with endogenous subclinical thyrotoxicosis.

PURPOSE: Endogenous subclinical thyrotoxicosis is diagnosed when a patient who is not taking exogenous thyroid hormone has a suppressed level of thyroid-stimulating hormone with normal levels of the free thyroid hormones thyroxine and triiodothyronine and other known causes of a suppressed thyroid-stimulating hormone level have been excluded. Although such a condition is caused by underlying thyroid disease, the specific nature and relative prevalence of these disorders and the utility of nuclear imaging and other studies in their detection remains unclear. PATIENTS AND METHODS: The authors performed a retrospective study of 50 patients with endogenous subclinical thyrotoxicosis. The results of the history and physical examination, thyroid nuclear scan, radioactive iodine uptake measurement, and thyroid antibody studies were reviewed. The results of the nuclear imaging and thyroid antibody studies were combined in an attempt to establish an underlying diagnosis for each patient. RESULTS: The thyroid nuclear imaging and antibody studies were used to establish a specific thyroid disorder in most of the patients (n = 39). These disorders included most commonly toxic multinodular goiter, various forms of autoimmune thyroid disease, and solitary toxic adenoma. A specific diagnosis was not determined in 11 patients. Therapy with I-131 radioactive iodine was administered to 14 of these patients, 13 of whom subsequently achieved a normal thyroid-stimulating hormone level. CONCLUSIONS: Most patients with endogenous subclinical thyrotoxicosis have underlying thyroid abnormalities that can be determined by nuclear imaging and, in selected cases, thyroid antibody studies.

Adult↗
PubMed1981

Blood mononuclear cells with suppressor activity in patients with thyroid disorders: increased levels of T gamma cells in subacute thyroiditis.

Blood T lymphocytes with suppressor activity [stable T cells, low affinity T cells and T cells with Fc receptors for IgG (T gamma cells)] were enumerated, using rosette tests, in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, silent thyroiditis, primary hypothyroidism, Graves' ophthalmopathy and subacute thyroiditis. General suppressor function, assessed as inhibition of pokeweed mitogen induced plasma cell generation by concanavalin-A stimulated T cells was measured in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. Suppressor T cell numbers were found to be essentially normal in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, Graves' ophthalmopathy, silent thyroiditis and hypothyroidism, although % T gamma cells were increased in 5 of the 7 patients with subacute thyroiditis tested. Suppressor cell function was normal in patients with graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. It is likely that the putative deficiency of suppressor T cells in thyroid autoimmunity is restricted to a few clones of cells allowing retention of thyroid directed effector cells. The mechanism for increased T gamma cells in subacute thyroiditis is unclear although likely to reflect either a physiological response to sensitization following thyroid antigen release or a non-specific effect of the viral infection.

Adolescent↗
PubMed2003

Thyroid cancer risk after thyroid examination with 131I: a population-based cohort study in Sweden.

Ionizing radiation is the only established cause of thyroid cancer, though the effect of diagnostic administration of (131)I on thyroid cancer risk appears minimal. The annual number of thyroid examinations using radioiodine is currently 5 per 1,000 individuals worldwide, so this issue is of public health importance. Our objective was to evaluate the excess risk of thyroid cancer following a range of known doses of (131)I administered for diagnostic purposes. We conducted a nationwide, population-based cohort study in Sweden including all 36,792 individuals who received (131)I for diagnostic purposes during 1952-1969 and were alive and free of thyroid cancer 2 years after exposure. Accrual of person-time at risk commenced 2 years after the first (131)I administration. Follow-up for cancer was to the end of 1998. Standardized incidence ratios (SIRs) were calculated as the ratio between the observed and expected numbers of thyroid cancers. Estimates were stratified by previous exposure to external radiation therapy to the neck, reason for thyroid examination, (131)I dose, sex, age at exposure and time since exposure. Thyroid cancers (n = 129) were diagnosed during 886,618 person-years at risk. Excess thyroid cancers were observed only among the 1,767 patients who reported previous external radiation therapy to the neck [SIR = 9.8, 95% confidence interval (CI) 6.3-14.6] and among those originally referred due to suspicion of a thyroid tumor (SIR = 3.5, 95% CI 2.7-4.4 for 11,015 patients without previous external radiation therapy). The 24,010 patients without previous exposure to external radiation therapy to the neck who were referred for a reason other than suspicion of a thyroid tumor received an estimated dose to the thyroid of 0.94 Gy. Among these patients, 36 thyroid cancers were observed compared to 39.5 expected (SIR = 0.91, 95% CI 0.64-1.26). We found no evidence that administration of (131)I for diagnostic purposes increases risk of thyroid cancer. However, our study included few patients under age 20, so the results apply primarily to exposure among adults. Our data suggest that protraction of dose may result in a lower risk than brief X-ray exposure of the same total dose.

Adolescent↗
PubMed1998

TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis.

OBJECTIVE: Autoimmunity plays an important role in the development of thyrotrophin (TSH) receptor antibodies and the pathogenesis of Graves' disease and Hashimoto's thyroiditis. On the other hand, subacute thyroiditis is a self-limited inflammatory disease of presumed viral aetiology. The aim of this study was to examine whether subacute thyroiditis triggers TSH receptor antibody-associated thyroid disorders. PATIENTS: We reviewed 1,697 patients with subacute thyroiditis seen between 1985 and 1995. DESIGN AND MEASUREMENTS: We measured antibodies which inhibit the TSH binding to the TSH receptor (TBIAb), thyroid stimulating antibodies (TSAb) and antibodies that block TSH action (TBAb). Other thyroid autoantibodies were also determined. RESULTS: TBIAb became positive in 38 patients following subacute thyroiditis. Thyroid function after the development of TBIAb appeared to be influenced by the bioactivity of the antibody. Hyperthyroidism developed in the presence of TSAb, and so did hypothyroidism in the presence of TBAb, although 21 patients did not have thyroid dysfunction despite high titres of TBIAb. Fifteen out of 17 patients recovered from hyperthyroidism or hypothyroidism after the disappearance of TBIAb sometimes even without medication. TBIAb-positive patients had a high incidence of a family history of thyroid disease and positive anti-thyroid microsomal antibodies. An ophthalmopathy similar to Graves' disease was also observed in 3 patients. CONCLUSIONS: Subacute thyroiditis may trigger autoreactive B cells to produce TSH receptor antibodies, resulting in TSH receptor antibody-associated thyroid dysfunction in some patients.

Adult↗