Thyroid Sections Research Articles

Pathology diagnosis of intraoperative frozen thyroid lesions assisted by deep learning

BackgroundThyroid cancer is a common thyroid malignancy. The majority of thyroid lesion needs intraoperative frozen pathology diagnosis, which provides important information for precision operation. As digital whole slide images (WSIs) develop, deep learning methods for histopathological classification of the thyroid gland (paraffin sections) have achieved outstanding results. Our current study is to clarify whether deep learning assists pathology diagnosis for intraoperative frozen thyroid lesions or not.MethodsWe propose an artificial intelligence-assisted diagnostic system for frozen thyroid lesions that applies prior knowledge in tandem with a dichotomous judgment of whether the lesion is cancerous or not and a quadratic judgment of the type of cancerous lesion to categorize the frozen thyroid lesions into five categories: papillary thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid tumor, and non-cancerous lesion. We obtained 4409 frozen digital pathology sections (WSI) of thyroid from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) to train and test the model, and the performance was validated by a six-fold cross validation, 101 papillary microcarcinoma sections of thyroid were used to validate the system’s sensitivity, and 1388 WSIs of thyroid were used for the evaluation of the external dataset. The deep learning models were compared in terms of several metrics such as accuracy, F1 score, recall, precision and AUC (Area Under Curve).ResultsWe developed the first deep learning-based frozen thyroid diagnostic classifier for histopathological WSI classification of papillary carcinoma, medullary carcinoma, follicular tumor, anaplastic carcinoma, and non-carcinoma lesion. On test slides, the system had an accuracy of 0.9459, a precision of 0.9475, and an AUC of 0.9955. In the papillary carcinoma test slides, the system was able to accurately predict even lesions as small as 2 mm in diameter. Tested with the acceleration component, the cut processing can be performed in 346.12 s and the visual inference prediction results can be obtained in 98.61 s, thus meeting the time requirements for intraoperative diagnosis. Our study employs a deep learning approach for high-precision classification of intraoperative frozen thyroid lesion distribution in the clinical setting, which has potential clinical implications for assisting pathologists and precision surgery of thyroid lesions.

A Flexible Mouse Model of Autoimmune Thyroiditis Induced by Immunization with an Adenovirus Containing Full-Length Thyroglobulin cDNA.

The main challenge in the "post-GWAS" era is to determine the functional meaning of genetic variants and their contribution to disease pathogenesis. Development of suitable mouse models is critical because disease susceptibility is triggered by complex interactions between genetic, epigenetic, and environmental factors that cannot be modeled by in vitro models. Thyroglobulin (TG) is a key gene for autoimmune thyroid disease (AITD) and several single nucleotide polymorphisms (SNPs) in the TG coding region have been associated with AITD. The classical model of experimental autoimmune thyroiditis (EAT), based on immunization of genetically susceptible mouse strains with purified TG protein in adjuvant, does not allow testing the impact of TG sequence variants on the development of autoimmune thyroiditis. Here we describe a protocol for the induction of EAT by immunization of mice susceptible to thyroiditis with an adenovirus vector carrying full-length human TG cDNA (Ad-TG EAT). We also provide support protocols for evaluation of autoimmune thyroiditis including serological assessment of TG antibodies, in vitro splenocyte proliferation assay and cytokines secretion, thyroid histology, and evaluation of thyroid lymphocytic infiltration by immunostaining. This protocol for EAT induction allows manipulation of the TG cDNA to introduce variants associated with AITD, enabling the testing of the functional effects of susceptible variants and their haplotypes on the immunogenicity of TG. Furthermore, the Ad-TG EAT mouse model is a valuable model for studying the interactions of the TG variants with non-genetic factors influencing AITD development (e.g., cytokines, iodine exposure) or with variants of other susceptible genes (e.g., HLA-DRβ1). © 2024 Wiley Periodicals LLC. Basic Protocol: Development of a mouse model of autoimmune thyroiditis induced by immunization with adenovirus containing full-length thyroglobulin cDNA Support Protocol 1: Splenocytes isolation Support Protocol 2: T cell stimulation and carboxyfluorescein diacetate succinimidyl ester (CFSE) based cell proliferation assay Support Protocol 3: Cytokine assays: measuring levels of interferon gamma (IFNγ) and interleukins IL-2, IL-4, and IL-10 in splenocyte supernatants Support Protocol 4: Evaluating thyroid histology and infiltration with immune cells: hematoxylin-eosin staining of mice thyroid glands Support Protocol 5: Immunohistochemistry of thyroid tissues: Immunofluorescence protocol of paraffin-embedded thyroid sections Support Protocol 6: Anti-thyroglobulin antibody measurement in mice sera by enzyme-linked immunosorbent assay (ELISA).

N-Nitrosomorpholine-induced oncocytic transformation in rat endocrine organs

BackgroundN-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats.MethodsThirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised.ResultsThere was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal.ConclusionsWe showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.

PSIX-8 Increased Expression of ST6GAL1 and Vegfa Mediate the Inflammatory Signaling Pathway in Feline Hyperthyroidism

Abstract Hyperthyroidism in cats is characterized by increased production of thyroid hormones including thyroxine (T4) and triiodothyronine (T3) and decreased levels of thyroid stimulating hormone (TSH). Older cats are at greater risk of developing hyperthyroidism. The common clinical signs include increased appetite, body weight loss, increased thirst and urination, periodic vomiting, and rapid heart rate. While the etiology of this disease in cats is not clear, it is likely multi-factorial and environmental, nutritional, and immunological factors have been implicated. We assessed the levels of inflammatory markers in thyroid tissue from cats housed in the Hill’s colony, at the natural end-of-life after living full lives. Cats that were diagnosed as having hyperthyroidism by a veterinarian (n = 10, 12.1-18.9 yr) had greater circulating fT4 when compared with controls. Control cats showed no signs of hyperthyroidism (n = 10, 10.9 to 18.6 yr). Histopathological analysis of hematoxylin and eosin-stained thyroid sections showed an increase in follicular cells as well as evidence of colloid reabsorption in cats with hyperthyroid when compared with controls. RNA was extracted from samples collected from cats and gene expression was investigated using the NanoString nCounter platform. Analysis was performed using the nSolver software. There was a significant increase in ST6GAL1 sialyltransferase when compared with controls (1.22 fold; P < 0.05). ST6GAL1 is an enzyme that can post-translationally modify glycoproteins by adding α2-6-linked sialic acids to them. ST6GAL1 can also regulate the NFκB inflammatory signaling pathway by promoting its sustained activation that can potentially lead to inflammation. In the present study we also saw a decrease in NFκB1/p105 (-1.14, ns), a protein that is processed to produce p50, an NFκB binding protein, but a small increase in NFκB2/p100 (1.06, ns), a protein that is processed to produce p52 of the NFκB signaling pathway in hyperthyroid cats when compared with controls. NFκB1 is a transcriptional repressor and a decline in its expression has been reported to contribute to increased inflammation. Further, an increase in NFκB2 may lead to increased activation of NFκB signaling as p52/RelB dimer is a transcriptional activator of NFκB signaling. There was also an increase in VEGFA in hyperthyroid when compared with controls (1.79 fold; P < 0.05). VEGF is an angiogenesis factor and increasing evidence indicates that angiogenesis sustains inflammation. VEGF is produced by endothelial cells, macrophages and activated T-cells and is also a potent chemoattractant for monocytes. While VEGF induces several pro-inflammatory genes including IL-8 and MCP-1, both were downregulated in hyperthyroid in the present study, indicating that the effects of VEGF were likely not mediated by pro-inflammatory IL-8 or MCP-1 in feline hyperthyroidism. Our data indicate that the etiology of hyperthyroidism involves multiple inflammatory signaling pathways and these may represent important therapeutic targets for reducing inflammation in feline hyperthyroidism.

Thyroxine restores hippocampal neurogenesis and synaptogenesis in a male rat model of carbimazole-induced hypothyroidism: a histological study

BackgroundAdult-onset hypothyroidism has a deleterious effect on hippocampal cognitive and memory functions. This study was performed to evaluate the possible therapeutic effect of thyroxine on hippocampus degeneration in an adult male rat model of carbimazole-induced hypothyroidism and the potentiality of spontaneous recovery. Thirty-two adult male albino rats were divided equally into four groups, as follows: I (control group), II (hypothyroidism group) received carbimazole (20 mg/kg) orally once daily for 4 weeks; III (recovery group) rats were managed as in group II, then left untreated for an additional 4 weeks to assess spontaneous recovery; and IV (thyroxine-treated group): hypothyroidism was induced as in group II, then rats received levothyroxine (20 µg/kg/day) orally for 4 weeks. Rats and their corresponding controls were sacrificed after 4 weeks in group II and after 8 weeks in groups III and IV. The levels of T3, T4, and TSH were measured. Hematoxylin and Eosin staining of thyroid and hippocampal sections was performed. Additionally, toluidine blue staining and immunohistochemical staining for PCNA, GFAP, and synaptophysin were applied to hippocampus sections. Both morphometric measurements and statistical analysis were performed.ResultsComparison of thyroxine-treated group with hypothyroidism and recovery groups revealed a significant reduction in TSH level and an increase in T3 and T4 levels, as well as improved histological architecture in both the thyroid and hippocampal sections. Hippocampal sections revealed a significant decrease in the mean area percent of GFAP, a significant increase in the mean number of PCNA-positive cells in the subgranular zone (SGZ); a niche for the adult neural stem cells (NSCs) in the hippocampus; and a significant increase in the mean area percent as well as the mean optical density of synaptophysin.ConclusionHippocampal degeneration is induced by hypothyroidism and can be restored by thyroxine replacement therapy, probably through neuronal cell preservation, synaptogenesis, and stimulation of neurogenesis in SGZ. On the other hand, spontaneous recovery from this degeneration was inadequate.

IL-9-Producing Th9 Cells Participate in the Occurrence and Development of Iodine-Induced Autoimmune Thyroiditis.

Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake.

Assessment of histopathological changes in the thyroid gland of fatal burn patients: A cross-sectional study

BackgroundSevere burn injury causes a marked hypermetabolic state in the body along with hypothyroidism. Here we aim to find out the morphological changes in the thyroid gland that may be an etiological factor of the hypothyroidism produced post severe burn injury. MethodsHistopathological study of the thyroid gland in 64 fatal burn cases of both sexes was conducted in our hospital. Thyroid samples collected during the autopsy were preserved in 10% formol saline and later stained using the hematoxylin and eosin staining method and the resulting sections were viewed under light microscopy. ResultsThe foremost pathological finding in the thyroid sections was the distortion of thyroid follicular architecture (59.37%). Their possible cause and the relationship between the distortion and period of survival after a burn injury and TBSA-B have been discussed. Other important findings like mononuclear cell infiltration, primarily in the interfollicular space (65.62%), clumping of the thyroglobulin (21.87%), and exhaustion of the thyroid follicles (17.18%) have been reported as well. ConclusionBurn injury has a metabolically damaging role on the thyroid gland, resulting in hypothyroidism which worsens over time. Hormonal replacement therapy is suggested.

Endocrine-disruptor endpoints in the ovary and thyroid of adult female rats exposed to realistic doses of di-(2-ethylhexyl) phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) is the world's most widely used polyvinyl chloride (PVC) plasticizer and is used in virtually every category of flexible PVC. In fact, DEHP is extensively used in food cosmetics and medical packaging. It has become a serious problem in recent years. DEHP can be absorbed into the human body through the air, food, water, and skin. The current study involved intraperitoneal injection of DEHP dissolved in corn oil once daily for 21 consecutive days to investigate the effects of DEHP on the thyroid and the reproductive system in female rats. Results show that ovarian hormones (progesterone and estrogen) decreased significantly in the rats treated with DEHP compared to control. This result is supported by the alteration of folliculogenesis, the decrease of the follicles viability, and the apoptosis of the granulosa cells observed on histological sections of ovary and thyroid in female rats exposed to low doses of DEHP. Histopathological study revealed that DEHP could damage thyroid tissue and disrupt these functions. We also observed cellular damage, particularly in the liver cells, and a significant increase in biochemical parameters such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group.

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Out of 206 members of the DGE's thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p<0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p<0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p<0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p<0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.

Protective effects of curcumin against thyroid hormone imbalance after gas explosion-induced traumatic brain injury via activation of the hypothalamic-pituitary-thyroid axis in male rats.

Gas explosion (GE)-induced traumatic brain injury (TBI) can affect thyroid hormone (TH) homeostasis in miners. This study evaluated the effects of hepatic transthyretin and hypothalamic-pituitary-thyroid (HPT) axis on thyroids and explored the protective effect and mechanism of curcumin on GE-induced TBI. Thirty rats were randomly divided into three groups (10 per group): first group (control group)-rats received GE treatment once; second group (GE group)-rats received GE treatment (200m from the source of the explosion once); third group (GE + Cur group)-rats received curcumin (Cur) by lavage at a dose of 100mg/kg/day once every other day for 7days after receiving GE. After GE, the pathological changes were analyzed by hemotoxylin and eosin staining, and the levels of serum reactive oxygen species (ROS), urine iodine (UI), THs, nuclear factor-kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and malondialdehyde (MDA) were analyzed using ELISA. Expression of proteins in the HPT axis of rats was examined by immunohistochemistry and Western blotting. We found that GE could induce pathologic changes in rat thyroid and liver. Serum levels of THs, NF-κB and serum redox state became unbalanced in rats after GE. GE could inhibit the biosynthesis and biotransformation of THs by affecting key HPT axis proteins. Additionally, GE reduced the level of hepatic transthyretin. Serum THs levels and thyroid sections were almost recovered to normal after curcumin treatment. The aforementioned key HPT axis proteins in the curcumin group showed opposite expression trends. In summary, GE affected THs balance while curcumin can protect against these injury effects by affecting TH biosynthesis, biotransformation, and transport, and inducing oxidative stress and inflammatory responses.

Comparative Study on Medicinal Natures (qi) of Black Ginseng, Red Ginseng, and Ginseng Leaves Based on Typical Deficiency-Heat Syndrome Rat Model.

To elucidate the medicinal nature of black ginseng (BG) by comparison of the effects of four Chinese herbs with different medicinal natures on the deficiency-heat syndrome rat model which was established by intragastric administration of traditional Chinese drugs with hot nature, the appearance indexes, biochemical indexes, and pathological sections of thyroid and stomach were examined. In addition, the seven short-chain fatty acids (SCFAs) in rat feces were also determined by headspace gas chromatography-mass spectrometry to reveal the action mechanism of the drugs with different natures. Results indicated that all the 4 drugs could exhibit similar actions in regulating the biochemical indexes of triiodothyronine (T3), thyroxine (T4), thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), and corticosterone (CORT) representing the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-adrenal (HPA) axes of the animal. However, cold-natured cortex phellodendri (HB) and ginseng leaves (GLs) showed stronger downregulation of the AChE activity of the nervous system. Red ginseng (RG) and BG tested exhibited stronger upregulation of the liver Na+-K+-ATPase activity. Principal component analysis (PCA) showed that GLs are similar to those of HB which belongs to the cold-nature drug, whereas BG showed closer to RG which attributes to a warm-nature drug. Thus, BG could be ascribed to a warm-nature drug. Further research disclosed that RG and BG mainly regulated the acetic acid and GL and HB primarily modulated the isovaleric acid and hexanoic acid in rat feces, which could be the features of drugs with warm or cold nature on the regulation of SCFAs in rats. It is for the first time that the medicinal nature of BG and its effect on the SCFAs were examined.

Clinical differences between IgG4 Hashimoto's thyroiditis and primary thyroid lymphoma.

BackgroundHashimoto’s thyroiditis (HT) can be divided into IgG4 HT and non-IgG4 HT based on IgG4 and IgG immunohistochemical staining. In clinical practice, it is often necessary to identify diseases such as primary thyroid lymphoma (PTL) and IgG4 HT when a patient presents with a rapidly enlarged thyroid. The aim of our study was to uncover the differential points between the two diseases.MethodsClinical information from 19 IgG4 HT and 10 PTL patients was obtained from the patients’ medical records, including age, sex, main clinical manifestation, thyroid functional status, the presence of serum anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and thyroid ultrasonography results. Thyroid sections from all patients were collected to detect IgG4 and IgG expression by immunohistochemical staining.ResultsThe IgG4 HT patients were significantly younger than those in the PTL group (39.68 ± 10.95 vs 66.20 ± 10.23 years, P < 0.001). There were no significant differences in the sex distribution or TgAb- or TPOAb-positive rates. The PTL group had a higher prevalence of clinical hypothyroidism than the IgG4 HT group (P = 0.016). In the PTL group, thyroid lesions were more likely to exhibit hypoechogenicity (6/6 vs 1/19, P < 0.001) on ultrasound images. In the PTL group, two patients met the immunohistochemical cut-off value of the criteria for IgG4 HT.ConclusionsSimply relying on immunohistochemistry for IgG4 cannot diagnose IgG4 HT correctly when a patient presents with rapid thyroid enlargement. A combination of clinical and pathological analyses will help distinguish IgG4 HT from PTL which may be with abundant IgG4-positive plasma cells.

Thyroglobulin regulates the expression and localization of the novel iodide transporter solute carrier family 26 member 7 (SLC26A7) in thyrocytes.

Solute carrier family 26 member 7 (SLC26A7), identified as a causative gene for congenital hypothyroidism, was found to be a novel iodide transporter expressed on the apical side of the follicular epithelium of the thyroid. We recently showed that TSH suppressed the expression of SLC26A7 and induces its localization to the plasma membrane, where it functions. We also showed that the ability of TSH to induce thyroid hormone synthesis is completely reversed by an autocrine negative-feedback action of thyroglobulin (Tg) stored in the follicular lumen. In the present study, we investigated the potential effect of follicular Tg on SLC26A7 expression and found that follicular Tg significantly suppressed the promoter activity, mRNA level, and protein level of SLC26A7 in rat thyroid FRTL-5 cells. In addition, follicular Tg inhibited the ability of TSH to induce the membrane localization of SLC26A7. In rat thyroid sections, the expression of SLC26A7 was weaker in follicles with a higher concentration of Tg, as evidenced by immunofluorescence staining. These results indicate that Tg stored in the follicular lumen is a feedback suppressor of the expression and membrane localization of SLC26A7, thereby downregulating the transport of iodide into the follicular lumen.

Histological Effects of Intermittent Fasting Concomitant with Levothyroxine Administration on the Thyroid Gland Structure of Adult Male Albino Rats

Introduction: Intermittent fasting is popularity and a promising approach for weight loss by daily restricted eating. Thyroid hormones controls body metabolism and accelerate the basal metabolic rate.Aim of this work: was designed to investigate the effect of intermittent fasting alone and when concomitant with levothyroxine on the histological characterization of the thyroid gland of the adult male albino rats.Material and methods: Twenty-four adult male albino rats were used and randomly divided into four equal groups. Group I (Control): Rats had free access to food and water. Group II (Fasting): Rats were deprived of food for 16 hrs daily with free access to water all over the day. Group III (levothyroxine): Each rat received levothyroxine (0.5μg/100g body weight /day) for three successive weeks via gastric tube and rats had free access to food and water all over the day. Group IV (Fasting +levothyroxine): Each rat received daily levothyroxine as in group III combined with food deprivation as in group II. At the end of the experiment, rats were sacrificed, and the thyroid glands were immediately obtained. The tissue samples were processed for paraffin and epon blocks. Thyroid sections were subjected to H&E, toluidine blue and Masson’s Trichrome. Also, immunohistochemical study was carried out for the detection of apoptosis and parafollicular cells. Results: The experimental intermittent fasting mildly affected the thyroid gland structure in comparison to the control group. In Levothyroxine treated group, most of follicles showed signs of degeneration in the form of their lining appeared vacuolated with dark nuclei and small or micro-follicles. While, fasting with levothyroxine showed marked obvious changes, flattened follicular cells with dark nuclei and vacuolated cytoplasm, desquamated foamy cells and scanty luminal colloid.Conclusion: The obtained results revealed marked degenerative changes of thyroid gland when intermittent fasting combined with levothyroxine.

Morphological and Immunohistochemical Changes in Thyroid Gland Due to Exposure of Formalin in Albino Rats

Background: Formaldehyde is the most widely used chemical in daily life; thus, chronic exposure to formaldehyde has been revealed to have negative effects on different organs in humans and animals. Objective: This research was designed to investigate variable thyroid changes arising from chronic formaldehyde exposure by measuring different histomorphometry parameters in accordance with estrogen receptor and S-100 protein expression. Materials & Methods: In this experiment, two hundred (200) rats were used and divided into two groups (100 male and 100 female), each group was subdivided into control and experimental groups each with 50 rats. The rats were exposed to formaldehyde using (20 ml =92.6ppm formaldehyde), 5hrs / d, for 21 days. Animals were sacrificed, and thyroid sections were examined for histomorphometry using H&E stain and immunohistochemistry for localization of estrogen receptor and S-100 protein Results: Significant decrease obtained in histomorphometrical measurements in the area of the colloids, area of follicles and width, height and number of the follicles in the cells of both experimental groups with no significant effect of gender in both control and experimental groups except in the height of the cells which showed significant decrease in female more than male. Formaldehyde exposure showed no significant effect on localization of estrogen receptor but significant increase of S-100 protein localization in both male and female groups. Conclusion: Formaldehyde had similar effect on histological structure of thyroid gland in both sexes causing disruption of thyroid follicles. Exposure of Formaldehyde had no effect on estrogen receptor but caused an increase in S-100 protein localization in both sexes. Key words: Formaldehyde, Rat, Estrogen receptor, S-100 protein

Contribution of Glycation and Oxidative Stress to Thyroid Gland Pathology-A Pilot Study.

The patho-mechanism of changes in the thyroid gland, including carcinogenesis, is a complex process, which involves oxidative stress. The goal of our investigation was to verify the extent of stress in the thyroid gland related to glycation. The study samples were comprised of blood sera, thyroid, and adipose tissue sections probed from 37 patients diagnosed with thyroid cancers and goiter. Using immuno-enzymatic and fluorometric assays we analyzed the content of advanced glycation end-products (AGEs), pentosidine, receptors for advanced glycation end-products (RAGE), scavenger receptor class (SR)-A, SR-B, glutathione, malondialdehyde and nitric oxide synthase. In addition to classic AGEs, a recent study detected the melibiose-derived glycation (MAGE) product. We demonstrated the presence of AGEs, MAGE and their receptors of the RAGE and SR-A. In addition, in the control samples of thyroid glands SR-B groups were detected as well as of pathological groups without noticeable tendency to antigen concentration in the area of carcinogenesis. Fluorescent AGEs correlate positively with glutathione, which supports the assumption that glycation stress leads to augmentation of oxidative stress and increase of the intensity of antioxidant mechanisms.

The protective effect of Spirulina versus vitamin E on Electromagnetic waves induced thyroid gland damage in the adult albino rat: a histological and immunohistochemical study

Introduction: widespread use of several electrical and telecommunication applications that produce EMFs is increasing rapidly. One of the most important organs which affected by numerous types of EMWs is the thyroid gland.Aim of the study: This study targets to explore effects of EMW exposure on the Thyroid and the protective influence of spirulina platensis and vit E . Material and methods: fifty healthy adult male albino rats were separated into five equal groups. Control group, EMW-exposed at which, rats were subjected to the effect of EMF 4 hours daily for a period of one month . EMW exposed- Spirulina treated group at which rats received Spirulina at a dosage of 300 mg/kg b.wt. just previous to EMW exposure daily for one month. EMW exposed - Vit E treated group at which , rats were subjected to EMF like that of group II and given Vit E orally at a dosage of 200 mg/kg. b.wt and a recovery group at which rats kept for one month after one month exposure to low frequency EMF. then The thyroid tissues were examined for histopathological and immunohistochemical changes. Results: group subjected to EMW showed disorganized & degenerated thyroid follicles .Numerous collagen fibers were present within the CT septa in the masson stained thyroid sections . Amount of PAS positive central colloid showed obvious decrease, with Strong KI-67 immunoreactivity and TGFᵦ1 immuno expression. Spirulina platensis and vit E reduces the effect of EMW on thyroid , but vit E revealed obvious increase in the PAS positive central colloid , significant decrease in collagen fibers, KI-67 immunoreactivity and TGFᵦ1 immuno expression compared with that in spirulina group.Conclusion: use of spirulina platensis during period of EMW exposure considered to have a protecting influence. The utilization of vit E has a more protection than spirulina

Histological, Morphometric and Hormonal Assay Study on the Effects of Phenobarbital Sodium on the Different Endocrine Glands in Adult Male Albino Rats

Introduction: Phenobarbital (PB) is a commonly used classical anticonvulsant drug. It is effective in treating partial tonic-clonic fits. Adverse effects of antiepileptic drugs on the endocrine glands were reported producing disturbed endocrine function. Aim of the work: was to study the possible effect of phenobarbital administration on rats' different endocrine glands using histological, hormonal assay and morphometric studies. Material and methods: fifty adult male albino rats were used, divided into 3 groups; A control group (I); consisted of 10 rats, phenobarbital group (II); contained 20 rats, each rat received 7.5 mg phenobarbital sodium / 100gm body weight orally for 30 days. PB withdrawal group (III); consisted of 20 rats, each received the same PB dose for 30 days orally and have been left without treatment for another 15 days. Results: examination of the pituitary, thyroid and adrenal gland sections of PB group showed dilatation and congestion of blood sinusoids, cytoplasmic vacuoles and irregularity of nuclei of pituitary secretory cells, marked decrease in both follicular size and colloid contents with destruction of the microvillus border of the thyroid follicles, increase in thicknesses of both adrenal cortex and medulla with disruption of the architecture of adrenal cortical layers. Examination of the PB withdrawal group showed evidence of improvement in the three glands as compared to the PB group. Conclusion: phenobarbital can cause harmful histopathological changes on the thyroid gland, adrenal cortex and pituitary gland and its withdrawal resulted in an improvement in these deleterious effects to a lesser extent.

Non-Surgical and Non-Radioiodine Techniques for Ablation of Benign Thyroid Nodules: Consensus Statement and Recommendation.

Thyroid nodules and cysts are frequently diagnosed in Germany with a prevalence of about 20% in young adults reaching up to 70% in older adults. Surgery is the standard treatment of symptomatic nodules, nodules with suspicion of malignancy and thyroid cancer. Radioiodine treatment is applied for autonomously functioning nodules. During the last years new non-surgical and non-radioiodine techniques have been introduced to treat thyroid nodules. These techniques include ethanol/polidocanol treatment, radiofrequency, microwave, and laser ablation, and high frequency ultrasound ablation. A significant reduction in nodule size could be documented for these techniques in several studies, but long-term outcome data are missing. Until now, there is no general consensus regarding the appropriate indications for these methods. For this reason, the Thyroid Section (German Society for Endocrinology), the Thyroid Working Committee (German Society for Nuclear Medicine), and the German Association of Endocrine Surgeons (CAEK) for the German Society of General and Visceral Surgery (DGAV) reviewed the respective literature, discussed the pro and cons and developed a consensus statement and recommendation to help physicians and patients in their decision making.

Expression of thyroglobulin by regulatory T cells in thyroid tissue.

The follicles are the minimal functional unit of the thyroid; the morphology and the function of each follicle can vary significantly. However, the reasons for the apparent follicular heterogeneity are poorly understood. Some tissue-resident regulatory T cells (Tregs) have a special phenotype that expresses unique molecules related to local tissue and regulates the tissue functions. The aim of this study was to identify the phenotype of thyroid Tregs and the roles of thyroid Tregs in thyroid physiological regulation. Thyroid tissue and peripheral blood samples were obtained from patients with benign thyroid nodules. Microarray-based gene expression, flow cytometry, immunofluorescence microscopy, and functional analysis of thyroid Tregs were performed. Here, we demonstrated that human thyroid Tregs expressed high level of thyroglobulin (Tg), both gene and protein. The immunofluorescence microscopy of thyroid section showed that the FOXP3+Tg+ cells concentrated in some of the thyroid follicles, at the side of the thyroid follicle. The peripheral blood Tregs expressed minimal levels of Tg, and low levels of Tg could effectively induce peripheral blood Tregs to express Tg, which was independent of thyrotropin simulation. Furthermore, the Tg secreted freely from thyroid Tregs that negatively regulated some thyroid-related genes expression. Our results revealed that the thyroid Tregs was a distinct population of Tregs, which expressed high level of Tg. The thyroid Tregs regulate thyroid function by Tg that is paracrine from the cells.