Thyroid Histology Research Articles

A thyroid peroxidase (TPO) mutation in dogs reveals a canid-specific gene structure

Congenital hypothyroidism with goiter (CHG) occurring as an autosomal recessive disorder is typically due to a defect of thyroid hormone synthesis (aka dyshormonogenesis). Thyroid peroxidase (TPO) is a multifunctional, heme-containing enzyme whose activity is required, and several inactivating TPO mutations causing CHG in humans and dogs have been described. Recently, two half-sib Spanish water dog (SWD) pups were diagnosed with CHG based on clinical signs, endocrine testing, and thyroid histology. TPO enzyme activity was absent, and immuno-cross-reactive TPO was undetectable in affected-dog thyroid tissue. A single guanosine insertion was observed in the first exon of the affected-dog TPO cDNA at a site not previously thought to be within the coding sequence. The insertion allele segregated with the deduced disease allele in the SWD breed and was not observed in unrelated dogs of various breeds. Comparison of the insertion site (an 8-nt poly-G tract) with the orthologous sequences of other mammalian reference genomes revealed that the octa-G tract obliterated the intron 1 splice acceptor site and the exon 2 translation initiation codon found at that position in other species. An in-frame ATG in strong Kozak consensus context was observed in the normal dog sequence 12 codons 5' of the usual mammalian start site, suggesting that dogs have lost the noncoding exon 1 demonstrated in human and mouse. A survey of TPO sequences in other carnivore species indicates that the poly-G tract necessitating an alternative translation initiation site is a canid-specific feature.

Effects of pubertal exposure to thiazole-Zn on thyroid function and development in female rats

Thiazole-Zn is a newly chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters. To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used. Postnatal days (PND) 22-old Sprague–Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200mg/kg/day for 20days. The thyroid endpoints and development endpoints were assessed. The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40mg/kg thiazole-Zn, but had no difference from controls at the other doses. Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell. No histological changes were observed in any of the other observed organs. In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups. These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity.

Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole

Determining the effects of chemicals on the thyroid system is an important aspect of evaluating chemical safety from an endocrine disrupter perspective. Since there are numerous chemicals to test and limited resources, prioritizing chemicals for subsequent in vivo testing is critical. 2-Mercaptobenzothiazole (MBT), a high production volume chemical, was tested and shown to inhibit thyroid peroxidase (TPO) enzyme activity in vitro, a key enzyme necessary for the synthesis of thyroid hormone. To determine the thyroid disrupting activity of MBT in vivo, Xenopus laevis larvae were exposed using 7- and 21-day protocols. The 7-day protocol used 18–357μg/L MBT concentrations and evaluated: metamorphic development, thyroid histology, circulating T4, circulating thyroid stimulating hormone, thyroidal sodium-iodide symporter gene expression, and thyroidal T4, T3, and related iodo-amino acids. The 21-day protocol used 23–435μg/L MBT concentrations and evaluated metamorphic development and thyroid histology. Both protocols demonstrated that MBT is a thyroid disrupting chemical at the lowest concentrations tested. These studies complement the in vitro study used to identify MBT as a high priority for in vivo testing, supporting the utility/predictive potential of a tiered approach to testing chemicals for TPO activity inhibition. The 7-day study, with more comprehensive, sensitive, and diagnostic endpoints, provides information at intermediate biological levels that enables linking various endpoints in a robust and integrated pathway for thyroid hormone disruption associated with TPO inhibition.

Histology of Thyroid and Parathyroid glands of cat

Histology of Thyroid and Parathyroid glands of cat

Role of Self-Tolerance and Chronic Stimulation in the Long-Term Persistence of Adenovirus-Induced Thyrotropin Receptor Antibodies in Wild-Type and Transgenic Mice

Graves'-like disease, reflected by thyrotropin receptor (TSHR) antibodies and hyperthyroidism in some mouse strains, can be induced by immunization with adenovirus-expressing DNA for the human TSHR or its A-subunit. The conventional approach involves two or three adenovirus injections at 3-week intervals and euthanasia 10 weeks after the first injection. To investigate TSHR antibody persistence in mice with differing degrees of self-tolerance to the TSHR A-subunit, we studied the effect of delaying euthanasia until 20 weeks after the initial immunization. Wild-type (WT) mice and transgenic (tg) mice expressing low intrathyroidal levels of the human TSHR A-subunit were immunized with A-subunit-adenovirus on two occasions; a second group of mice was immunized on three occasions. Sera obtained 4, 10, and 20 weeks (euthanasia) after the initial immunization were tested for thyrotropin (TSH) binding inhibition (TBI), antibody binding to TSHR A-subunit protein-coated enzyme-linked immunosorbent assay (ELISA) plates, and thyroid stimulating antibody activity (TSAb; cyclic adenosine monophosphate [cAMP] generation). Serum thyroxine (T4) and thyroid histology were studied at euthanasia. THE majority of WT mice retained high TSHR antibody levels measured by TBI or ELISA at euthanasia but only about 50% were TSAb positive. Low-expressor tgs exhibited self-tolerance, with fewer mice positive by TBI or ELISA and antibody levels were lower than in WT littermates. In WT mice, antibody persistence was similar after two or three immunizations; for tgs, only mice immunized three times had detectable TSAb at 20 weeks. Unlike our previous observations of hyperthyroidism in WT mice examined 4 or 10 weeks after immunization, all mice were euthyroid at 20 weeks. Our findings for induced TSHR antibodies in mice, similar to data for human thyroid autoantibodies, indicate that the parameters that contribute to the concentration of the antibody and thereby play a critical role in long-term persistence of TSHR antibodies are the degree of self-tolerance to the TSHR and chronic stimulation.

Thyroid cancer in patients with acromegaly: a case–control study

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18years, matched for age and sex and with nodule (s) ≥1cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p=0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.

Long term persistence of thyrotropin receptor antibodies in wild-type and transgenic mice in a Graves' disease model.

Background: Graves'-like disease, reflected by TSHR antibodies and hyperthyroidism in some mouse strains, can be induced by immunization with adenovirus expressing DNA for the human thyrotropin receptor (TSHR) or it's A-subunit. The conventional approach involves two or three adenovirus injections at three-weekly intervals and euthanasia 10 weeks after the first injection. In order to investigate TSHR antibody persistence in mice with differing degrees of self-tolerance to the TSHR A-subunit, we studied the effect of delaying euthanasia until 20 weeks after the initial immunization. Methods: Wild-type mice and transgenic mice expressing low intrathyroidal levels of the human TSHR A-subunit were immunized with A-subunit-adenovirus on two occasions; a second group of mice was immunized on three occasions. Sera obtained 4, 10 and 20 weeks (euthanasia) after the initial immunization were tested for TSH binding inhibition (TBI), antibody binding to TSHR A-subunit protein-coated ELISA plates and thyroid stimulating antibody activity (TSAb; cAMP generation). Serum thyroxine and thyroid histology were studied at euthanasia. Results: The majority of wild-type mice retained high TSHR antibody levels measured by TBI or ELISA at euthanasia but only about 50% were TSAb positive. Low expressor transgenics exhibited self-tolerance, with fewer mice positive by TBI or ELISA and antibody levels were lower than in wild-type littermates. In wild-type mice, antibody persistence was similar after two or three immunizations; for transgenics, only mice immunized three times had detectable TSAb at 20 weeks. Unlike our previous observations of hyperthyroidism in wild-type mice examined 4 or 10 weeks after immunization, all mice were euthyroid at 20 weeks. Conclusions: Our findings for induced TSHR antibodies in mice, similar to data for human thyroid autoantibodies, indicate that the parameters that contribute to the concentration of the antibody and thereby play a critical role in long term persistence of TSHR antibodies are the degree of self-tolerance to the TSHR and chronic stimulation.

Excess Iodine and High-Fat Diet Combination Modulates Lipid Profile, Thyroid Hormone, and Hepatic LDLr Expression Values in Mice

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 μg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.

Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAF(V600E)) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAF(V600E), the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAF(V600E) expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAF(V600E) rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAF(V600E) mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications.

Effets de la restriction alimentaire appliquée à des rates adultes sur la croissance osseuse et la structure histologique de la thyroïde chez leurs jeunes

Study purposeOur objective was the study of the development and the maturation of pups whose mothers were subjected to intermittent fasting. Materials and methodsEight pregnant female Wistar rats were distributed into two groups of four adult females. The rats of the first group were subjected to intermittent fasting beginning on the 14th day of gestation and continued 21 days after parturition. The rats of the second group were normally fed. The young of both groups of rats were sacrificed at the age of 21 days. ResultsThe pups of the female rats submitted to food restriction showed a reduction of the body weight (–35%), of the thyroid iodine content (P<0.001) and of segment thyroxin (P<0.05). The histological study revealed that these pups presented colloid depletion of this follicular thyroid, non-anastomosing trabeculae, cortical bone thinning, decreased bone mineral content, absence of osteoid formation and decreased number of osteoclasts. ConclusionDietary restriction imposed on adult rats, from gestation, led to the installation in their pups of a state of malnutrition and a description of thyroid histology. This thyroid abnormality is associated with hypothyroidism that led, at least in part, to the collapse of the ability to regulate bone remodeling.

Sunitinib-Induced Hypothyroidism Is due to Induction of Type 3 Deiodinase Activity and Thyroidal Capillary Regression

Anticancer treatment with the tyrosine kinase inhibitor sunitinib causes thyroid dysfunction. Our objective was to investigate the time course and underlying mechanisms of sunitinib-induced thyroid dysfunction. Thyroid function tests of 83 patients on sunitinib were collected retrospectively for their total treatment duration between January 2006 and November 2009 and prospectively in 15 patients on sunitinib for 10 wk. Additionally, thyroid function and histology were assessed in rats on sunitinib (8 d; n = 10) and after sunitinib withdrawal (11 d; n = 7) and compared with controls (n = 7). Patients were seen at a university outpatient oncology clinic. Patients and Animals: Patients with metastatic renal cell carcinoma or gastrointestinal stromal tumors participated in the clinical study and Wistar Kyoto rats were used in the rat study. Sunitinib was taken according to a 4 wk "on," 2 wk "off" treatment regimen. Blood samples for measurement of thyroid function were collected at baseline and at wk 4 and 10. In rats, blood, liver, and thyroid were collected to assess thyroid hormones, deiodinase activity, and thyroid histology. TSH and free T(4) levels, deiodinase activity, and thyroid histology were assessed. Forty-two percent of patients in the retrospective study developed elevated TSH levels. Prospective analysis showed increased TSH levels within 10 wk of treatment, accompanied by a decreased T(3)/rT(3) ratio. In rats, serum T(4) and T(3) decreased, hepatic type 3 deiodinase activity increased, and thyroid histology showed marked capillary regression, which all but thyroid hormones reversed after sunitinib withdrawal. Sunitinib induces hypothyroidism due to alterations in T(4)/T(3) metabolism as well as thyroid capillary regression.

Thyroid gland invasion in laryngopharyngeal squamous cell carcinoma: Prevalence, endoscopic and CT predictors

The authors studied the prevalence of histological thyroid gland invasion in laryngopharyngeal cancer and the preoperative endoscopic and CT signs predictive of this invasion. Retrospective study of patients with laryngopharyngeal squamous cell carcinoma (T3 and T4) treated by total laryngectomy or total laryngopharyngectomy associated with concomitant total thyroidectomy or ipsilateral lobectomy and isthmectomy. Eighty-seven patients were included. Eleven patients (12.6%) presented thyroid gland invasion. Subglottic tumour extension greater than or equal to 10mm (P=0.008) and cricoid cartilage destruction on CT (P=0.001) were statistically correlated with histological thyroid gland invasion. An intact appearance of the laryngeal cartilages on CT was associated with a low probability of thyroid gland invasion. Thyroid gland invasion must not be underestimated in patients with advanced laryngopharyngeal cancer. Preoperative CT is an essential part of the preoperative work-up. Thyroidectomy must not be performed systematically.

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

BackgroundSeveral DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases. In this study we were aiming (1) to identify potential markers for papillary thyroid carcinomas through meta analysis of public microarray data and (2) to confirm these markers in an independent dataset using an independent technology.MethodsWe adopted a meta analysis approach for four publicly available microarray datasets on papillary thyroid carcinoma (PTC) nodules versus nodular goitre (NG) from N2-frozen tissue. The methodology included merging of datasets, bias removal using distance weighted discrimination (DWD), feature selection/inference statistics, classification/crossvalidation and gene set enrichment analysis (GSEA). External Validation was performed on an independent dataset using an independent technology, quantitative RT-PCR (RT-qPCR) in our laboratory.ResultsFrom meta analysis we identified one gene (SERPINA1) which identifies papillary thyroid carcinoma against benign nodules with 99% accuracy (n = 99, sensitivity = 0.98, specificity = 1, PPV = 1, NPV = 0.98). In the independent validation data, which included not only PTC and NG, but all major histological thyroid entities plus a few variants, SERPINA1 was again markedly up regulated (36-fold, p = 1:3*10-10) in PTC and identification of papillary carcinoma was possible with 93% accuracy (n = 82, sensitivity = 1, specificity = 0.90, PPV = 0.76, NPV = 1). We also show that the extracellular matrix pathway is strongly activated in the meta analysis data, suggesting an important role of tumor-stroma interaction in the carcinogenesis of papillary thyroid carcinoma.ConclusionsWe show that valuable new information can be gained from meta analysis of existing microarray data deposited in public repositories. While single microarray studies rarely exhibit a sample number which allows robust feature selection, this can be achieved by combining published data using DWD. This approach is not only efficient, but also very cost-effective. Independent validation shows the validity of the results from this meta analysis and confirms SERPINA1 as a potent mRNA marker for PTC in a total (meta analysis plus validation) of 181 samples.

Thyroid gland lesions in organohalogen contaminated East Greenland polar bears (Ursus maritimus)

Thyroid gland histology was examined in 20 organohalogen contaminant (OHC)-exposed East Greenland polar bears (Ursus maritimus). OHC concentrations measured in subcutaneous adipose tissue were between 3556 and 28,670 ng g−1 lw for polychlorinated biphenyls (ΣPCB51), 9 and 3403 ng g−1 lw for the sum of organochlorine pesticides (hexachlorocyclohexanes, hexachlorobenzene, chlordanes, dichlorodiphenyltrichloroethanes, and dieldrin), and from 21 to 130 ng g−1 lw for polybrominated diphenyl ethers. Histological examinations revealed that 12 of the bears (10 males aged 3–19 years and two females aged 4–7 years) had normal thyroid tissue while eight bears (40%) of varying ages and genders (three males aged 3–9 years and five females aged 4–25 years) showed clear histological lesions including parafollicular C-cell proliferation, nodular hyperplasia, and interstitial fibrosis. No significant differences were found in prevalence of thyroid gland lesions between males and females. Similarly, no marked difference was found in mean age between individuals with and without lesions. There was no significant difference in OHC mean concentrations between males and females or between individuals with and without lesions. Despite no documented relationship to OHC concentrations in adipose tissue, it is worth noting that the lesions were similar to that of OHC exposed lab and wildlife contaminated mammals. Since the lesions were not associated with age or gender, other environmental factors such as energetic stress and autoimmunity/genetic predisposition also need to be considered. It is therefore possible that OHCs, in combination with other environmental and intrinsic factors described in the literature, may interfere with the hypothalamic–pituitary–thyroid axis (HPT axis) resulting in endocrine perturbations in East Greenland polar bears.

Triclosan and Thyroid-Mediated Metamorphosis in Anurans: Differentiating Growth Effects from Thyroid-Driven Metamorphosis in Xenopus laevis

In a previously reported study, we used a standard metamorphosis anuran model to assess potential effect of the antibacterial agent triclosan (TCS) on normal prometamorphic Xenopus laevis. Results indicated that environmentally relevant TCS concentrations did not alter the normal course of thyroid-mediated metamorphosis in this standard anuran model. However, to examine potential effects of TCS exposure during premetamorphosis and to distinguish between effects on metamorphosis and effects on growth, a longer term TCS exposure study was conducted. Standard Nieuwkoop and Faber (NF) stage 47 X. laevis larvae were exposed for 32 days (ca. NF stage 59-60) via flow-through to four different concentrations of TCS: < 0.2 (control), 0.8, 3.1, 12.5, or 50.0 μg TCS/l. Primary endpoints were survival, hind limb length, body length (whole; snout-to-vent), developmental stage, wet whole body weight, thyroid histology, plasma thyroid hormone (TH) concentrations, TH receptor beta (TRβ), and type II and III deiodinase (DI-2 and DI-3) expression. Endpoints measured to evaluate effects on thyroid-mediated metamorphosis including developmental stage, thyroid histology, TRβ expression, DI-2 and DI-3 expression, and thyroid gland 3,5,3',5'-tetraiodothyronine (T4) and plasma T4 and 3,5,3'-triiodothyronine (T3) levels were not affected by TCS exposure. However, increased larval growth based on whole body length (0.78, 12.5, and 50 μg TCS/l), snout-vent length (3.1 and 12.5 μg TCS/l), and whole body weight (0.8, 12.5, and 50.0 μg TCS/l) was observed following 32-day TCS exposure. These results indicated that TCS exposure during pre- and prometamorphosis increased larval growth but did not alter the normal course of metamorphosis in X. laevis. The increased growth associated with TCS exposure was not unexpected and is generally consistent with the presence of reduced bacterial stressors in culture.

Assessment of antithyroid activity of 2,8-disulfanyl-1,9-dihydro-6H-purin-6-one in vitro and in vivo

2,8-Disulfanyl-1,9-dihydro-6H-purin-6-one has been examined in vitro and in vivo, for its potential antithyroid effects. It exhibited stable higher order complexation with iodine in vitro, which is a sign of its possible antithyroid activity. The blood assays of rats were carried out using radioimmunoassay technique to determine free triiodothyronine and thyroxin levels and with ELISA method for thyroid stimulating hormone concentration; which showed a decrease in the former two hormone levels and increase in the latter, for the animals treated with 2,8-disulfanyl-1,9-dihydro-6H-purin-6-one as compared to the control groups. Similarly, thyroid histology of the treated animals depicted hyperactive gland conditions with little colloid material and cylindrical shape of follicular epithelium as compared to the normal cuboidal epithelium with sufficient stores of colloid material in the control animals, which confirms the antithyroid activity of the 2,8-disulfanyl-1,9-dihydro-6H-purin-6-one. The results were also compared with the animals treated with methimazole (1-methyl-1H-imidazole-2-thiol), the well known antithyroid drug and it was found that 2,8-disulfanyl-1,9-dihydro-6H-purin-6-one is more potent than methimazole as far as hormonal variations are concerned.

Thymulin Gene Therapy Prevents the Histomorphometric Changes Induced by Thymulin Deficiency in the Thyrotrope Population of Mice

There is evidence of the existence of a bidirectional relationship between the thymus gland and the thyroid axis. Since the thymic peptide thymulin possesses hypophysiotropic activity, we undertook the task of assessing the histomorphometric changes induced by thymulin deficiency on the thyrotrope population of normal mice and the action of neonatal thymulin gene therapy on the thyrotropin (TSH)-cells of nude mice. C57BL/6 mice were subjected to immunoneutralization of circulating thymulin from postnatal day 1 to the end of the study (postnatal day 32) by intraperitoneal injections of rabbit anti-factor thymulin serum (α-FTS) and normal rabbit serum in controls. Also, neonatal thymulin gene therapy was implemented in athymic nude mice using an adenoviral vector expressing a gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral intramuscular (i.m.) injection of either RAd-FTS or RAd-GFP (the latter being the control vector). The pituitaries were immunostained for TSH. Thymulin immunoneutralization severely reduced serum thymulin (p < 0.01). We detected a significant (p < 0.05) decrease in cell size (CS) and volume density (VD) with a nonsignificant decrease in cell density (CD) in C57BL/6 in both males and females. A single neonatal i.m. injection of RAd-FTS markedly increased the circulating levels of serum thymulin in the athymic mice and increased the CD (p < 0.05), CS (p < 0.01) and VD (p < 0.01) of the thyrotrope population in nu/nu mice. Thyroid histology was not affected. Our results suggest a possible modulating effect of thymulin on the thyrotrope population.

The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system

Event Abstract Back to Event The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system Claudia Lorenz1*, Achim Trubiroha1, Ilka Lutz1 and Werner Kloas1, 2 1 Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Department of Ecophysiology and Aquaculture, Germany 2 Humboldt University Berlin, Department of Endocrinology, Germany In a long-term exposure, the synthetic gestagen levonorgestrel (LNG), a widely-used contraceptive compound was tested for effects on thyroid hormone (TH) dependent metamorphosis of Xenopus laevis. Using a flow-trough culture system, premetamorphic X. laevis tadpoles were treated with four LNG concentrations (10-11 M, 10-10 M, 10-9 M, 10-8 M) over the period of completion of metamorphosis. Recording of developmental time, analysis of gene expression patterns using qPCR and histopathological examination of thyroid glands clearly evidenced a thyroid-disrupting effect of LNG in developing tadpoles (Lorenz et al., 2011). However, mechanisms underlying LNG effects remained unclear but were evidently not consistent with a classic goitrogenic mode of action. To elucidate the mode of LNG action, additional in vivo and ex vivo experiments were performed and are still ongoing. Gene expression patterns were investigated in brain-pituitary, thyroid and tail tissue. Three days of in vivo exposure did not change TSHβ gene expression in brain-pituitary tissue. By contrast, LNG affected transcription levels in thyroid tissue. Thyroidal mRNA levels of sodium-iodine-symporter (NIS) were reduced by 10-8 M LNG treatment. Moreover, exposure to 10-9 and 10-8 M LNG caused a concomitant rise of the TH activating deiodinase type 2 (D2) and the TH inactivating D3. Ex vivo LNG treatment of thyroid glands for 48 hours did not change NIS and D2 gene expression. Instead, LNG at 10-8 M significantly induced mRNA levels of D3, indicating a direct effect of LNG on thyroidal gene expression. First results of an ex vivo tail culture suggest further LNG effects on deiodinase gene expression and indicate that LNG directly acts on TH target tissues as well. In summary, our data demonstrate for the first time adverse effects of a synthetic gestagen on the thyroid system of amphibians. Evidently, LNG acts on several key-structures of the TH system, namely the thyroid gland and the tail representing a TH target tissue. The tissue-specific modulation of TH bioavailability by changing D mRNA expression seems to be one mode of LNG action. Furthermore, histopathological evaluation and gene expression data from long-term LNG exposure indicate a disruption of TH feedback. References Lorenz, C., Contardo-Jara, V., Pflugmacher, S., Wiegand, C., Nützmann, G., Lutz, I., and Kloas, W. (2011). The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system. Toxicol. Sci. doi: 10.1093/toxsci/kfr159. Keywords: deiodinase, Gene Expression, progestin, sodium iodine symporter, thyroid histology, TSH Conference: ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology, Ann Arbor, United States, 11 Jul - 13 Jul, 2011. Presentation Type: Invited Symposium Topic: Endocrine disruption Citation: Lorenz C, Trubiroha A, Lutz I and Kloas W (2011). The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system. Front. Endocrinol. Conference Abstract: ISAREN 2011: 7th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology. doi: 10.3389/conf.fendo.2011.03.00027 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Jul 2011; Published Online: 09 Aug 2011. * Correspondence: Miss. Claudia Lorenz, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Department of Ecophysiology and Aquaculture, Berlin, Germany, claudia.lorenz@igb-berlin.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Claudia Lorenz Achim Trubiroha Ilka Lutz Werner Kloas Google Claudia Lorenz Achim Trubiroha Ilka Lutz Werner Kloas Google Scholar Claudia Lorenz Achim Trubiroha Ilka Lutz Werner Kloas PubMed Claudia Lorenz Achim Trubiroha Ilka Lutz Werner Kloas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Follicular lesions of the thyroid: A retrospective study of 1,348 fine needle aspiration biopsies

Fine needle aspiration (FNA) has proven to be an effective tool in management of patients with thyroid nodules. However, the diagnosis of follicular patterned lesions can be challenging. The surgical and cytopathology computer database at a large referral medical center was searched for cases that had both cytologic and histologic thyroid accessions from January 2004 to November 2008. A total of 1,255 histologic thyroid specimens and 2,776 thyroid FNA biopsies were retrieved for review. Histologically, 272 overt malignancies were identified; 20 (7.4%) were follicular carcinomas. Cytologically, 1,348 cases were follicular-patterned lesions, comprising 1,044 cases of "benign follicular nodules" (BFN), 137 cases of "follicular lesions of undetermined significance" (FLUS), and 167 cases of "suspicious for follicular neoplasm" (SFN). Seventy-nine (7.5%) of BFN, 23 (16.8%) of FLUS, and 65 (38.9%) of SFN cases had histologic follow-up. Overt malignancy, a cystic papillary carcinoma, was identified histologically in only one case of BFN, for a negative predictive value of 98.7%. Overt malignancy was identified histologically in two cases of FLUS, both follicular variant of papillary carcinoma, for a positive predictive value of 8.7%. Overt malignancy was identified histologically in 14 cases of SFN, for a positive predictive value of 21.5%. Five follicular carcinomas were identified histologically in the SFN category, all minimally invasive. Incidental ("occult") papillary microcarcinoma were identified histologically in all three categories. In this study, the risk of overt malignancy increases from 1.3%, to 8.7%, to 21.5% for BFN, FLUS, and SFN, respectively. All follicular carcinomas identified histologically occurred in the SFN category and all were minimally invasive. Papillary microcarcinomas can occur in any of the three diagnostic categories.

Screening of thyroid gland histology in organohalogen-contaminated glaucous gulls (Larus hyperboreus) from the Norwegian Arctic

The associations between blood organohalogen contaminant (OHC) concentrations and thyroid gland histology were studied in 10 adult female glaucous gulls (Larus hyperboreus) from the Norwegian Arctic (Bjørnøya) during the incubation period. This histological investigation was undertaken as previous glaucous gull studies from the same area reported negative relationships between circulating OHC concentrations and thyroid hormone levels. Organohalogen concentrations have previously been associated with altered blood plasma thyroid hormone concentrations, as a result of parenchymal thyroid gland alterations and perturbation of the hypothalamic-pituitary-thyroid (HPT)-axis. In this study, PCB (range: 186–1027 ng g−1ww), DDT (77–203 ng g−1ww) and chlordane (18–65 ng g−1ww) concentrations dominated the blood plasma OHC profile in incubating female glaucous gulls. High density of small follicles accompanied by follicular epithelial cell proliferations was seen in thyroid glands in seven of 10 gulls. Focal thyroiditis and nodular hyperplasia were found in two birds. No significant differences in plasma OHC concentrations were noted between gulls exhibiting high density of small follicles and cell proliferations and those birds not showing histological changes. Based on these findings, data suggest that the histological changes in thyroid glands of OHC-contaminated female glaucous gulls may be due to natural variance, although an OHC-induced thyroid stimulating hormone (TSH) perturbation resulting in epithelial cell hyperplasia and increased follicular density cannot be ruled out and remains to be verified. Hence, a large-scale histological study is required, in order to elaborate the potential linkage between changes in thyroid gland histology, OHC exposure and regulation of the HPT-axis in the Arctic-breeding glaucous gull.