Thyroid Morphology Research Articles

Thyroid Dysfunction in Patients with Metastatic Carcinoma Treated with Sunitinib: Is Thyroid Autoimmunity Involved?

Sunitinib is a tyrosine kinase inhibitor (TKI) inducing thyroid dysfunction, but the precise mechanism(s) involved remains to be explained, including the role of thyroid autoimmunity. The objective of this study was to evaluate thyroid function, parameters of autoimmunity, and thyroid ultrasound findings in patients with metastatic cancer and normal thyroid function/autoimmunity before the initiation of sunitinib therapy. This was a prospective, observational cohort study. Twenty-seven patients with metastatic carcinomas at comparable tumor stages were evaluated over 12-18 months after initiating therapy with sunitinib given at a daily oral dose of 50 mg for four weeks (ON), followed by one to two weeks off therapy (OFF). Serum thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and antithyroglobulin (TgAb), and antithyroid peroxidase (TPOAb) autoantibodies were measured in all cases. Thyroid morphology and volume were evaluated by echo-color Doppler ultrasound. A total of 16/27 patients (60%) became hypothyroid (TSH range 7-114 mIU/L) within 30-120 days of therapy. The thyroid volume decreased in 24/27 (89%) patients (from M = 14.6 mL, SD = 6.4 mL to M = 3.8 mL, SD = 2.6 mL after 12 months; p < 0.001), together with the appearance of mild to severe hypoechogenicity. TPOAb (40-3000 IU/mL) became detectable in 7/27 (25%) patients, and TPOAb-positive patients displayed a higher degree of hypothyroidism and volume reduction. The progression-free survival (PFS) was significantly longer in patients developing TPOAb (10.8 months) than in the other group of patients (5.8 months). These data confirm the thyroid inhibitory effect of sunitinib, in keeping with the key role of kinases in controlling thyroid function and growth. However, the novel appearance of TPOAb in a subgroup of patients with more severe hypothyroidism and longer survival indicates that sunitinib may also trigger/exacerbate thyroid autoimmunity contributing to thyroid failure. The development of TPOAb was associated with a longer PFS.

Absence of A Thyroid Phenotype in Sortilin-Deficient Mice

The Vps10p family member sortilin is expressed in thyroid epithelial cells where it contributes to recycling of the thyroid hormone precursor thyroglobulin (Tg), a process that is thought to render hormone release more effective. Here we investigated the functional impact of sortilin in the thyroid gland using sortilin-deficient mice. We measured free T4, thyroid-stimulating hormone (TSH) and Tg serum levels and studied thyroid morphology in 14 sortilin-deficient (Sort1)(-/-)and 12 wildtype (WT) mice. Serum free T4 levels did not differ between Sort1(-/-)and WT females but were significantly lower in Sort1(-/-)males compared with WT (P = .0424). Neither serum TSH nor Tg levels differed between Sort1(-/-)and WT mice, regardless of sex. On the same line, no thyroid histology differences were observed. Our findings seem to exclude a role of sortilin in thyroid hormone secretion, although it is possible that the absence of sortilin may result in a thyroid phenotype if combined with other molecular defects of thyroid hormone synthesis and secretion or under iodine deficiency.

Effects of Excess Fluoride and Iodide on Thyroid Function and Morphology.

Exposure to high levels of iodide in Cangzhou, Shandong Province, China has been associated with increased incidence of thyroid disease; however, whether fluoride can affect the thyroid remains controversial. To investigate the effects of excess fluoride, we evaluated thyroid gland structure and function in rats exposed to fluoride and iodide, either alone or in combination. Five-week-old Wistar rats (n = 160 total) were randomly divided into eight groups: three groups that were given excess fluoride (15, 30, or 60 ppm F); one group given excess iodide (1200 μg/L I); three groups given excess iodide plus fluoride (1200 μg/L I plus 15, 30, or 60 ppm F); and one control group. The serum concentrations of the thyroid hormones TT3 and TT4 on day 150 were significantly reduced for certain fluoride groups; however, no significant differences were observed in concentrations for the pituitary hormone TSH among any groups. Hematoxylin and eosin staining revealed that iodide causes an increase in the areas of the colloid lumens and a decrease in the diameters of epithelial cells and nuclei; however, fluoride causes an increase in nuclear diameters. The damage to follicular epithelial cells upon fluoride or iodide treatment was easily observed by transmission electron microscopy, but the effects were most dramatic upon treatment with both fluoride and iodide. These results suggest that iodide causes the most damage but that fluoride can promote specific changes in the function and morphology of the thyroid, either alone or in combination with iodide.

Exposure to non-ionizing radiation provokes changes in rat thyroid morphology and expression of HSP-90.

Non-ionizing radiation at 2.45 GHz may modify the morphology and expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Diathermy is the therapeutic application of non-ionizing radiation to humans for its beneficial effects in rheumatological and musculo-skeletal pain processes. We used a diathermy model on laboratory rats subjected to maximum exposure in the left front leg, in order to study the effects of radiation on the nearby thyroid tissue. Fifty-six rats were individually exposed once or repeatedly (10 times in two weeks) for 30 min to 2.45 GHz radiation in a commercial chamber at different non-thermal specific absorption rates (SARs), which were calculated using the finite difference time domain technique. We used immunohistochemistry methods to study the expression of HSP-90 and morphological changes in thyroid gland tissues. Ninety minutes after radiation with the highest SAR, the central and peripheral follicles presented increased size and the thickness of the peripheral septa had decreased. Twenty-four hours after radiation, only peripheral follicles radiated at 12 W were found to be smaller. Peripheral follicles increased in size with repeated exposure at 3 W power. Morphological changes in the thyroid tissue may indicate a glandular response to acute or repeated stress from radiation in the hypothalamic-pituitary-thyroid axis. Further research is needed to determine if the effect of this physical agent over time may cause disease in the human thyroid gland.

English

The histology and ultrastructure of thyroid gland of White Fulani (Zebu) cattle were examined during the postnatal developmental period to show if variations in morphology exist with age and in relation to tropical climate. Eight prepubertal and ten pubertal cattle of abattoir origin were used to carry out this study. Histologically, the thyroid consisted of well-developed capsule, interlobular connective tissue, follicular and parafollicular cells from prepubertal to pubertal age of 5 to 7 years. The follicular cells were cuboidal in prepubertal period with some variations, became predominantly columnar in pubertal age of 2 to 4 years and highly flattened cells were common in the older pubertal animals of&nbsp; 5 to 7 years. The colloid was observed in the lumen at all age and was PAS-positive with abundant peripheral vacuoles in the pubertal age of 2 to 4 years. Significant variations (p˂0.05) in structure of the thyroids were observed at all age and the follicular size and number of follicles increased as the cattle matured. Follicular height was reduced significantly in the older pubertal cattle of 5 to 7 years. Ultrastructurally, the follicular cells showed highly dilated cisternae of rough endoplasmic reticulum which decreased with age. Flattened follicular cells seen in the older pubertal cattle contained few cytoplasmic organelles and microvilli. Apically placed pseudopods and blebs were commonly observed in the pubertal age of 2 to 4 years. Lysosomal bodies increased with age of development. The parafollicular cells were encountered frequently in the prepubertal age than in the older cattle. They consisted of numerous dense secretory granules which increased in number with age. The present results suggest an optimum thyroid function during the pubertal. Our findings would be useful in interpreting changes in thyroid morphology during experimental and pathological conditions. &nbsp; Key words: &nbsp;Cattle, postnatal thyroid, histology, ultrastructure.

Influence of thyroid function on the outcome of percutaneous coronary intervention in euthyroid patients with coronary artery disease

Background Thyroid hormonal disturbance plays an essential role in coronary artery disease (CAD) development and progress. Few studies have detected the relation between percutaneous coronary intervention (PCI), thyroid gland function, and morphology. We aimed to assess the influence of baseline thyroid function tests on the outcome of PCI in euthyroid patients with CAD, and to detect the effect of PCI on the thyroid function and ultrasound features. Patients and methods This study included 113 clinically euthyroid patients with stable CAD. Serum free T3, serum free T4, thyroid-stimulating hormone (TSH), thyroid-stimulating hormone index, free T3/T4 ratio, anti-thyroperoxidase (TPO), and high-sensitivity C-reactive protein had been measured before, and then 24 h and 3 months after PCI. The morphology of thyroid was evaluated through thyroid ultrasound before and 3 months after PCI. Results One day after PCI, there was a significant increase in serum FT3 and serum FT4 and no significant change in the serum TSH compared with just before PCI (P Conclusion A state of euthyroid hyperthyroxinemia was detected 24 h after PCI. A state of thyroid hormone resistance was detected 3 months after PCI. Higher TSH and measured echogenicity index independently predicted unfavorable outcome after 24 h. Lower FT3 and higher FT4 levels independently predicted unfavorable outcomes after 3 months.

Correlation analysis between type 2 diabetes mellitus and thyroid nodules in elderly patients

Objective To investigate the prevalence of thyroid nodules in elderly patients(age≥80years)with type 2diabetes mellitus(T2DM),and to analyze the correlation between thyroid nodules and type 2diabetes mellitus.Methods The study included two groups:one group included 103 patients with T2DM(diabetic group)and the other group included 103 patients without T2DM(control group).Information including clinical history,fasting plasma glucose(FPG),thyroid hormone,and ultrasonic finding of thyroid glands was collected for both groups.The clinical features of thyroid nodules were compared between the two groups and their relationship with other indices was analyzed.Results(1)The prevalence rate of thyroid nodules in diabetic group was greatly higher than that of the control group(84.47% vs 70.59%).The proportion of patients with multiple nodules was as high as 80.46% in the diabetic group.Presence of thyroid nodule was significantly associated with patient ages(χ2=7.060,P0.05),but not with gender,body mass index(BMI),or serum glucose level.(2)The positive rate of thyroid dysfunction in the diabetic group was significantly higher than that in the control group(15.53% vs6.80%,P0.05).The prevalence rates of sub-clinical hypothyroidism were similar between the two groups.T3 and T4levels of thyroid function in the diabetic group were significantly lower than those in the control group(P0.05),and the thyroid stimulating hormone(TSH)levels were similar between the two groups.Conclusion Elderly patients(age≥80years)have a higher liability for thyroid disease,which may affect the control and prognosis of diabetes.It is recommended for those patients to receive regular check-up for thyroid function and morphology changes.

Proof of concept of the WOMED model of benign thyroid disease: Restitution of thyroid morphology after correction of physical and psychological stressors and magnesium supplementation

BackgroundThe aim of this study was to investigate the influence of a combined supplementation with magnesium, selenium and coenzyme Q10 on the morphology of the thyroid in patients with benign diseases. The clinical examination and treatment approach aims additionally at treating musculoskeletal and psychological stress. MethodsA group of 8 patients (5 with hyperthyroidism, 3 with hypothyroidism) who initially attended a public institution received additional treatment at our private institution. The basic pharmacological treatment, i.e. substitution or thyreostatic, was kept unchanged. The inclusion of patients required good quality ultrasound images to be available. ResultsInitially the changes of the musculoskeletal system were corrected. Following this, stress components were also treated. After a period of 2–4years of supplementation we observed a normalization of thyroid morphology as evidenced on ultrasound while at the same time there was a reduction of perfusion intensity. Thyroid antibody titers decreased in the majority of cases. Failure of the treatment was seen in 2 cases of chronic thyroiditis that was present for more than 10years. The ultrasound images of these patients suggest a possible fibrosis. ConclusionsIn spite of the limitation due to the small number of cases, our observational study has delivered proof of concept for our examination and treatment model for benign thyroid disease. General significanceOur results challenge validity of the prevailing dogma of a destructive unstoppable “autoimmune” destructive process of the gland. At the same time it shows new therapeutic options for patients with thyroid disease.

The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation

BackgroundThe aim of this study was to discern whether a relation between biochemical parameters, sonography and musculoskeletal data exists in cases of hyperthyroidism and whether they are modifiable through supplementation with selenomethionine and magnesium citrate as well as by acupuncture and manual medicine methods. ResultsA direct correlation between whole blood selenium and serum magnesium was found in subjects without thyroid disease and in menopausal women while it was reversed in cases of thyroid diseases as well as in patients with depression, infection, and in infertile women. Vascularization indices were elevated in cases of newly diagnosed benign thyroid diseases. Musculoskeletal changes i.e. lateral tension and idiopathic moving toes, as well as situations of physical and psychological stress and minor trauma and infection led to an increase of vascularization. Magnesium levels correlated negatively with these two conditions. The supplementation brought a reduction of the vascularization indices and reduced the incidence of idiopathic moving toes. Treatment of lateral tension required manual medicine methods and acupuncture (gastrocnemius). A small subgroup of patients showed a further reduction of hyper-vascularization after receiving coenzyme Q10. ConclusionsWe interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10.

Adli Otopsilerde Rastlantısal Tiroit Patolojileri

Amaç: Otopsilerde en sık karşılaşılan rastlantısal lezyonların arasında tiroit hiperplazilerinin olduğu ve gizli tiroit mikrokarsinomaları ile de karşılaşıldığı bilinmektedir.Çalışmamızda, bölgemizde otopsileri yapılarak ölümün medikolegal yönden değerlendirildiği olgularda, tiroit örneklemesi yapılabilen çocuk ve erişkin yaş grubundaki tiroit lezyonlarının ortaya konulması amaçlandı.Yöntem: Bu çalışmada, Nisan 2009- Nisan 2010 tarihleri arasında İzmir Adli Tıp Kurumu Morg İhtisas Dairesi’nde adli otopsileri yapılan olgulardan prospektif olarak tiroit bezinden doku örneği alınması planlanmıştır. Çalışma süresince kokuşma bulguları gözlenmeyen 210 olgunun tiroit örneği alınmıştır. Çalışmamızda, otopsileri yapılan adli olguların; yaş, cinsiyet, ölüm nedenleri, ölüm orijinleri, tiroit bezi ağırlıkları ve morfolojisi, tiroit patolojileri ve tanımlanan lezyonun primer ölüm nedeni ya da ölümle potansiyel ilişkisi olup olmadığı araştırılmıştır. Veriler Windows SPSS 11.0 bilgisayar programında değerlendirilmişir. Bulgular: 210 olgunun yaş ortalaması 49,44±18,25 olup, olguların %76,7’si (n=161) erkek idi. İncelenen doku örneklerinde; tiroit organ ağırlığı ortalaması 40,71±27,95 gr. olarak ölçüldü ve 96 olguda histopatolojik inceleme sonucu bir lezyona rastlandı. İyot alımının yetersiz olmadığı kabul edilen bölgemizde, adli otopsilerde örnek alınan olgularda tiroit bezi patolojilerinin prevalansının % 45 olduğu gözlendi.Tiroit bezi ağırlıklarının yaş ile hafif düzeyde korelasyon gösterdiği belirlendi (P=0.002 ve r=0.219) ve cinsiyet ile ilişkisinin olmadığı görüldü. En sık rastlanan lezyonlar sırasıyla; noduler hiperplazi (%29,5), lenfositik tiroidit (%5,7) ve Hashimoto tiroiditi (%5,7) olup bir olguda akciğer küçük hücreli kanser metastazı ve bir olguda da konjenital boyun kitlesi (brankial kist) belirlendi.Sonuç: Adli otopsilerde tiroit bezinin rutin olarak incelenmesi, ölüm sebeplerini belirlemede faydalı olabileceği gibi gizli kalan tiroit hastalıklarının ve özellikle tiroit malignitelerinin profilinin belirlenmesi ile toplumsal sağlık verilerine de önemli katkı sağlayacaktır.Anahtar kelimeler: Tiroit, adli otopsi, histopatoloji, rastlantısal lezyonlar.

Hypothalamic–pituitary thyroid axis alterations in female mice with deletion of the neuromedin B receptor gene

Neuromedin B, a peptide highly expressed at the pituitary, has been shown to act as autocrine/paracrine inhibitor of thyrotropin (TSH) release. Here we studied the thyroid axis of adult female mice lacking neuromedin B receptor (NBR-KO), compared to wild type (WT) littermates. They exhibited slight increase in serum TSH (18%), with normal pituitary expression of mRNA coding for α-glycoprotein subunit (Cga), but reduced TSH β-subunit mRNA (Tshb, 41%), lower intra-pituitary TSH content (24%) and increased thyroid hormone transporter MCT-8 (Slc16a2, 44%) and thyroid hormone receptor β mRNA expression (Thrb, 39%). NBR-KO mice exhibited normal thyroxine (T4) and reduced triiodothyronine (T3) (30%), with no alterations in the intra-thyroidal content of T4 and T3 or thyroid morphological changes. Hypothalamic thyrotropin-releasing hormone (TRH) mRNA (Trh) was increased (68%), concomitant with a reduction in type 2 deiodinase mRNA (Dio2, 30%) and no changes in MCT-8 and thyroid hormone receptor mRNA expression. NBR-KO mice exhibited a 56% higher increase in serum TSH in response to an acute single intraperitoneal injection of TRH concomitant with a non-significant increase in pituitary TRH receptor (Trhr) mRNA at basal state. The phenotype of female NBR-KO mice at the hypothalamus–pituitary axis revealed alterations in pituitary and hypothalamic gene expression, associated with reduced serum T3, and higher TSH response to TRH, with apparently normal thyroid morphology and hormonal production. Thus, results confirm that neuromedin B pathways are importantly involved in secretory pathways of TSH and revealed its participation in the in vivo regulation of gene expression of TSH β-subunit and pituitary MCT8 and Thrb and hypothalamic TRH and type 2 deiodinase.

Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

Reproduction Symposium: does grazing on biosolids-treated pasture pose a pathophysiological risk associated with increased exposure to endocrine disrupting compounds?

Biosolids (processed human sewage sludge), which contain low individual concentrations of an array of contaminants including heavy metals and organic pollutants such as polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB), and polychlorinated dibenzodioxins/polychlorinated dibenzofurans known to cause physiological disturbances, are increasingly being used as an agricultural fertilizer. This could pose a health threat to both humans and domestic and wild animal species. This review summarizes results of a unique model, used to determine the effects of exposure to mixtures of environmentally relevant concentrations of pollutants, in sheep grazed on biosolids-treated pastures. Pasture treatment results in nonsignificant increases in environmental chemical (EC) concentrations in soil. Whereas EC concentrations were increased in some tissues of both ewes and their fetuses, concentrations were low and variable and deemed to pose little risk to consumer health. Investigation of the effects of gestational EC exposure on fetal development has highlighted a number of issues. The results indicate that gestational EC exposure can adversely affect gonadal development (males and females) and that these effects can impact testicular morphology, ovarian follicle numbers and health, and the transcriptome and proteome in adult animals. In addition, EC exposure can be associated with altered expression of GnRH, GnRH receptors, galanin receptors, and kisspeptin mRNA within the hypothalamus and pituitary gland, gonadotroph populations within the pituitary gland, and regional aberrations in thyroid morphology. In most cases, these anatomical and functional differences do not result in altered peripheral hormone concentrations or reproductive function (e.g., lambing rate), indicating physiological compensation under the conditions tested. Physiological compensation is also suggested from studies that indicate that EC effects may be greater when exposure occurs either before or during gestation compared with EC exposure throughout life. With regard to human and animal health, this body of work questions the concept of safe individual concentration of EC when EC exposure typically occurs as complex mixtures. It suggests that developmental EC exposure may affect many different physiological systems, with some sex-specific differences in EC sensitivity, and that EC effects may be masked under favorable physiological conditions.

Identification of parathyroid glands: anatomical study and surgical implications

While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.

Associations between thyroid dysfunction and chronic kidney disease

Abstract Background and Aims. The interactions between kidney and thyroid functions are well established: thyroid hormones are necessary for the maintenance of electrolyte and water homeostasis and kidney is involved in the regulation of thyroid hormones metabolism. The aim of our study was to estimate the prevalence of thyroid dysfunction in patients with diabetes mellitus and chronic kidney disease (CKD). Material and Method. 23 patients with diabetes mellitus and CKD in pre-dialysis phase were recruited for this study. All subjects were investigated with thyroid ultrasound and laboratory tests to determine thyroid function, including: serum triiodothyronine (T3), free thyroxine (free T4), thyroid-stimulating hormone (TSH) and antithyroid peroxidase antibodies (ATPO). Results were compared with the same measurements in 21 patients with diabetes mellitus but without CKD. Results. The prevalence of goiter (52.17% vs. 19.04%, p&lt;0.05), subclinical hypothyroidism (23.80% vs. 9.52%, p&lt;0.05), hypothyroidism (8.69% vs. 4.76 %, p&lt;0.05) and low T3 syndrome (23.80% vs. 0.00% p&lt;0.05) were significant high in diabetic patients with CKD compared with patients with diabetes mellitus but without CKD. Conclusions. We observed high prevalence of thyroid morphology abnormalities and thyroid function disorders in diabetic patients with CKD. Low T3 syndrome and subclinical hypothyroidism are the most frequently thyroid function disorders in CKD patients.

Thyroglobulin Suppresses Thyroid-Specific Gene Expression in Cultures of Normal But Not Neoplastic Human Thyroid Follicular Cells

It was shown in the rat thyroid that thyroglobulin (Tg) stored in the follicular lumen is a potent regulator of thyroid-specific gene expression to maintain the function of individual follicles. However, the actions of Tg as a regulatory molecule in human thyroid have not been studied. Our objective was to determine the effect of Tg on gene expression in normal and diseased human thyroid and to examine whether the proposed model of negative-feedback autocrine regulation of thyroid function by Tg is applicable in the human as well as the rat. Primary cultures of human thyrocytes were established from normal thyroid, Graves' disease thyroid, adenomatous goiter, follicular adenoma, and papillary carcinoma tissues obtained during surgery. Cells were stimulated with physiologic (ie, follicular) concentrations of Tg, and mRNA and protein expression of genes involved in thyroid hormonogenesis were evaluated. The effects of Tg on thyroid-specific gene expression were also assessed in 2 human papillary carcinoma cell lines. Transcript levels of genes participating in thyroid hormone biosynthesis were significantly reduced by Tg in thyrocyte cultures derived from normal and Graves' thyroid, but not in cultures derived from thyroid neoplasms and adenomatous goiter. It was confirmed that Tg acts as a negative-feedback regulator of gene expression in human thyrocytes, suggesting that Tg signaling may constitute a common mechanism for maintaining thyroid homeostasis in species with follicular thyroid morphology. However, certain diseases of intrinsic thyroid overgrowth appear to be associated with an escape from the regulatory mechanism of Tg.

Age-dependent changes in gross and histological morphology of the thyroid gland in South Australian koalas (Phascolarctos cinereus)

Studies characterising the thyroid gland structure of koalas are limited and have not previously been undertaken in South Australian populations. Hence, this study aimed to describe the thyroid gland morphology of koalas from the Mount Lofty region, South Australia. Results showed that thyroid gland morphology was highly variable between individual koalas (n = 36), ranging from that considered typical for healthy mammals, in which small colloid-filled follicles were lined by cuboidal epithelium, to that consistent with colloidal goitre, in which macrofollicles distended with colloid were lined by flattened epithelium. Juvenile koalas more frequently showed typical thyroid gland morphology than adults, with significantly higher thyroid follicle density (P &lt; 0.05) and a higher proportion of follicles lined by cuboidal epithelium compared with flattened epithelium (P &lt; 0.05). Thyroid glands of most adult koalas were characterised by colloidal macrofollicles (P &lt; 0.01), and classified as colloidal goitre. There were no significant differences in thyroid gland morphology based on health status or sex of koalas. These findings suggest that an age-dependent colloidal goitre occurs in adult koalas, which is unlikely to have ill effects and may be associated with the low metabolic rate of this species, or exposure to a dietary goitrogen.

Graves' disease in children.

Graves' disease is the most frequent cause of hyperthyroidism in children. It may occur at any time during childhood, but its frequency increases with age, peaking during adolescence. Antithyroid drugs (ATDs; methimazole or carbimazole) are usually recommended as the initial treatment and are generally well tolerated. The overall frequency of relapse is higher in children than in adults, with remission achieved in only 30% of children after a first course of treatment for about 2 years. More prolonged medical treatment may increase the remission rate to up to 50%. The identification of factors predictive of relapse, such as severe biochemical hyperthyroidism at diagnosis and the absence of other autoimmune conditions, has facilitated the identification of patients requiring long-term ATD treatment or alternative therapy. Alternative treatments (mostly radioactive iodine, rather than thyroidectomy) are considered in cases of relapse after an appropriate course of ATD, lack of compliance or ATD toxicity. Future research on the management of patients should focus on improving compliance with drug treatment through educational strategies, improving knowledge of the long-term effects of the various treatment options on thyroid gland morphology and function, potential morbidities, future pregnancies and quality of life. A better understanding of the physiopathology of this disorder should improve remission rates and patient management and lead to the identification of factors predicting the likelihood of remission.

&lt;b&gt;Histological and immunohistochemical study of the thyroid gland of the broad-snouted caiman (&lt;i&gt;Caiman latirostris&lt;/i&gt;)&lt;/b&gt; - doi: 10.4025/actascibiolsci.v35i4.18444

The broad-snouted caiman, Caiman latirostris, is widely distributed in countries of South America. In Brazil it is considered an endangered species because of natural habitat destruction and illegal hunting. In reptiles, the thyroid gland plays an integral part in ecdysis, reproduction, tail regeneration, growth, endocrine function and metabolism rate. The aim of the present study was to characterize the thyroid gland morphology of C. latirostris, based on histochemical and immunohistochemical techniques. The thyroid glands were fixed in Bouin's fluid and serial cross sections were stained with hematoxylin-eosin, Mallory’s trichrome, periodic acid-Schiff (PAS) and Alcian blue (AB pH 1.5 and 2.5). The immunohistochemical technique for 5-HT-IR cells was used. The thyroid gland has a dense irregular connective tissue forms a capsule enveloping the gland. There are several follicular acini of varying size lined by simple cuboidal or columnar epithelium in the thyroid gland. The follicles are connected by interfollicular connective tissue which contains blood vessels. We observed the presence of lymph nodes around the entire gland. There was a positive PAS reaction and negative AB reaction in the colloid. 5-HT-IR cells were detected around the follicle cells. No striking morphological differences were observed between C. latirostris and other domesticated mammals.

Disruption of transforming growth factor-β signaling in thyroid follicular epithelial cells or intrathyroidal fibroblasts does not promote thyroid carcinogenesis

Transforming growth factor β (TGF-β) members, pleiotropic cytokines, play a critical role for carcinogenesis generally as a tumor suppressor in the early cancer development, but as a tumor promoter in the late stage of cancer progression. The present study was designed to clarify the role for TGF-β signaling in early thyroid carcinogenesis using the conditional Tgfbr2(floxE2/floxE2) knock-in mice, having 2 loxP sites at introns 1 and 2 of Tgfb2r gene. When these mice were crossed with thyroid peroxidase (TPO)-Cre or fibroblast-specific protein-1 (FSP1)-Cre, the resultant mice, Tgfbr2(tpoKO) and Tgfbr2(fspKO), lost TGF-β II receptor expression (thereby TGF-β signaling) specifically in the thyroid follicular epithelial cells or fibroblasts, respectively. The thyroid morphology was monitored up to 52 weeks in these mice, showing no tumor development, except one Tgfbr2(tpoKO) mouse developing follicular adenoma like-lesion. Our data suggest that TGF-β signaling in mesenchymal or follicular epithelial cells of the thyroid does not appear to function as a tumor suppressive barrier at the early stage of thyroid carcinogenesis.