2-iodohexadecanal induces autophagy during goiter involution.

BACKGROUND: Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that 2-IHDA inhibits several thyroid parameters and it has been postulated as intermediary on the action of iodide function. OBJECTIVE: To explore different mechanisms involved during the involution of the hyperplastic thyroid gland of Wistar rats towards normality induced by 2-IHDA. METHODS: Goiter was induced by the administration of MMI for 10 days, then the treatment was discontinued and Wistar rats were injected with 2-IHDA or KI. RESULTS: During involution, 2-IHDA treatment reduced PCNA expression compared to spontaneous involution. KI treatment caused an increase of Caspase-3 activity and TUNEL-positive cells. In contrast, 2-IHDA failed to alter this value but induced an increase of LC3B expression. KI but not 2-IHDA led to an increase in peroxides levels, catalase and glutathione peroxidase activity. CONCLUSIONS: We demonstrated that 2-IHDA, in contrast to iodide, did not lead to an increase in oxidative stress or apoptosis induction, indicating that the involution triggered by 2-IHDA in Wistar rats, is primarily due to the inhibition of cell proliferation and the induction of autophagy.

Maintaining the thyroid gland in mutant thyroglobulin-induced hypothyroidism requires thyroid cell proliferation that must continue in adulthood.

Congenital hypothyroidism with biallelic thyroglobulin (Tg protein, encoded by the TG gene) mutation is an endoplasmic reticulum (ER) storage disease. Many patients (and animal models) grow an enlarged thyroid (goiter), yet some do not. In adulthood, hypothyroid TGcog/cog mice (bearing a Tg-L2263P mutation) exhibit a large goiter, whereas adult WIC rats bearing the TGrdw/rdw mutation (Tg-G2298R) exhibit a hypoplastic thyroid. Homozygous TG mutation has been linked to thyroid cell death, and cytotoxicity of the Tg-G2298R protein was previously thought to explain the lack of goiter in WIC-TGrdw/rdw rats. However, recent studies revealed that TGcog/cog mice also exhibit widespread ER stress-mediated thyrocyte death, yet under continuous feedback stimulation, thyroid cells proliferate in excess of their demise. Here, to examine the relative proteotoxicity of the Tg-G2298R protein, we have used CRISPR-CRISPR-associated protein 9 technology to generate homozygous TGrdw/rdw knock-in mice in a strain background identical to that of TGcog/cog mice. TGrdw/rdw mice exhibit similar phenotypes of defective Tg protein folding, thyroid histological abnormalities, hypothyroidism, and growth retardation. TGrdw/rdw mice do not show evidence of greater ER stress response or stress-mediated cell death than TGcog/cog mice, and both mouse models exhibit sustained thyrocyte proliferation, with comparable goiter growth. In contrast, in WIC-TGrdw/rdw rats, as a function of aging, the thyrocyte proliferation rate declines precipitously. We conclude that the mutant Tg-G2298R protein is not intrinsically more proteotoxic than Tg-L2263P; rather, aging-dependent difference in maintenance of cell proliferation is the limiting factor, which accounts for the absence of goiter in adult WIC-TGrdw/rdw rats.

A case-control study on the association of mineral elements exposure and thyroid tumor and goiter.

Thyroid tumor and thyroid goiter are prevalent disease around the world. In this case-control study, we investigated the association between exposure to a total of twelve mineral elements and thyroid disease as well as thyroid functions. Participants with thyroid tumor or goiter (N = 197) were matched with a healthy population (N = 197) by age (± 2 years old) and same sex. Questionnaires were used to collect data about the demographic characteristics and information of subjects. Serum and urine samples were collected simultaneously for each of the subjects. Mineral elements, iodine level of urine and levels of the total seven thyroid function indexes in serum were detected respectively. Conditional logistic regression was applied to estimate the associations between mineral elements and the risk of thyroid tumor and goiter through single-element models and multiple-element models. Multiple linear regression was used to evaluate relationships between mineral elements and percentage changes of thyroid functions. Higher concentrations of mineral elements in the recruited population were found in this study than other comparable studies, and the levels of chromium (Cr), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), selenium (Se), antimony (Sb), thallium (Tl) and lead (Pb) in the case group were lower than the control group. According to the single-element models, Cr, Mn, Ni, Sb and Tl showed significant negative associations with the risk of thyroid tumor and goiter, and, Cd showed nonmonotonic dose response. Cd and mercury (Hg) showed a nonmonotonic percentage change with T4, while Tl was associated with the increased FT4 in the control group. Therefore, Cd, Hg and Tl may disturb the balance of thyroid function to some extent, and Cr, Mn, Ni, Cd, Sb, and Tl may become potential influencing factors for the risk of thyroid tumor and goiter.

Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1ß in Hashimoto's thyroiditis but not in Graves' disease.

T helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1ß are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1ß in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto's thyroiditis (HT) and 8 cases of Graves' disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1ß was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1ß expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1ß expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1ß (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1ß expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.

Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics.

The thyroid is a major component of the endocrine system and its pathology can cause serious diseases, e.g., papillary carcinoma (PC). However, the carcinogenic mechanisms are poorly understood and clinical useful biomarkers are scarce. Therefore, we determined if there are quantitative patterns of molecular chaperones in the tumor tissue and circulating exosomes that may be useful in diagnosis and provide clues on their participation in carcinogenesis. Hsp27, Hsp60, Hsp70, and Hsp90 were quantified by immunohistochemistry in PC, benign goiter (BG), and normal peritumoral tissue (PT). The same chaperones were assessed in plasma exosomes from PC and BG patients before and after ablative surgery, using Western blotting. Hsp27, Hsp60, and Hsp90 were increased in PC in comparison with PT and BG but no differences were found for Hsp70. Similarly, exosomal levels of Hsp27, Hsp60, and Hsp90 were higher in PC than in BG, and those in PC were higher before ablative surgery than after it. Hsp27, Hsp60, and Hsp90 show distinctive quantitative patterns in thyroid tissue and circulating exosomes in PC as compared with BG, suggesting some implication in the carcinogenesis of these chaperones and indicating their potential as biomarkers for clinical applications.

Regulation of thyroid sodium-iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species.

Na+ /I- symporter (NIS) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (MMI) for 5 and 21 days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1 day (R1d), after 5 (R1d-5d) or 21 (R1d-21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time-dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d-5d, it was still high in R1d-21d. On the other hand, iodide uptake was rapidly down-regulated in R1d-21d, but not in R1d-5d, suggesting that the increased TPO activity in R1d-21d led to increased intraglandular organified iodine (I-X), which is known to inhibit iodide uptake. Since TGFß has been shown to mediate some effects of I-X, we evaluated TGFß and TGFß receptor mRNA levels, which were increased in R1d-21d. Moreover, it has been demonstrated that TGFß stimulates NOX4. Accordingly, our data revealed increased NOX4 expression and H2 O2 generation in R1d-21d. Finally, we evaluated the effect of H2 O2 on NIS function and mRNA levels in PCCL3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I-X, TGFß, NOX4 and increased ROS production.

[MICROELEMENT STATUS IN CHILDREN WITH ENLARGED THYROID GLAND IN WEST KAZAKHSTAN REGION].

Aim of research - analysis of content of microelements in hair of children with thyromegaly living in the West Kazakhstan region. 159 school children of 6-12 years constantly living in this region were studied. Thyroid volume was measured by ultrasonography using an ultrasound scanner and evaluated according to body surface area and the gender in accordance with the WHO recommendations (2007). Microelements were measured by inductively coupled plasma mass spectrometry on NexION 300D (PerkinElmer Inc., USA). Excess value of the content of boron at 32.29% and silicon at 21.44% was found in children with goiter compared with those from control group. There was a reduction of cadmium at 37.38%, manganese - 26.48%, lead - 47%, vanadium - 15.5% compared with children with the normal volume of the thyroid gland. Correlation analysis showed a positive association of thyroid volume and hair trace elements Cu (r=0.423; p=0.001) and Si (r=0.202; p=0.01) and between I in hair and Hg (r=0.2978; p=0.001). The results of the multiple regression analysis revealed that the amount of thyroid is positively related to the concentration of copper and silicon in hair, and in less degree negatively with vanadium. The effect of these elements is 23%. Also found a positive dependence of iodine in the hair from indicators of mercury and negative from beryllium. Children with goiter show increased content of boron and silicon in hair and the decreased level of cadmium, manganese, lead, vanadium. The content of iodine in hair of children depends on the indicators of mercury and beryllium.

Assessing the potential impact on the thyroid axis of environmentally relevant food constituents/contaminants in humans.

Occurrence and mode of action of potentially relevant goitrogens in human nutrition and their mode of action (MOA) are reviewed, with special focus on the anionic iodine uptake inhibitors perchlorate (PER), thiocyanate (SCN) and nitrate (NO3). Epidemiological studies suggest persistent halogenated organic contaminants and phthalates as well as certain antimicrobials to deserve increased attention. This also applies to natural goitrogens, including polyphenols and glucosinolates, food constituents with limited data density concerning human exposure. Glucosinolates present in animal feed are presumed to contribute to SCN transfer into milk and milk products. PER, SCN and NO3 are well-investigated environmental goitrogens in terms of MOA and relative potency. There is compelling evidence from biomarker monitoring that the exposure to the goitrogens SCN and NO3 via human nutrition exceeds that of PER by orders of magnitude. The day-to-day variation in dietary intake of these substances (and of iodide) is concluded to entail corresponding variations in thyroidal iodide uptake, not considered as adverse to health or toxicologically relevant. Such normal variability of nutritional goitrogen uptake provides an obvious explanation for the variability in radioactive iodine uptake (RAIU) measurements observed in healthy individuals. Based on available data, a 20 % change in the thyroidal uptake of iodide is derived as threshold value for a biologically meaningful change induced by perchlorate and other goitrogens with the same MOA. We propose this value to be used as the critical effect size or benchmark response in benchmark dose analysis of human RAIU data. The resulting BMDL20 is 0.0165 mg/kg bw/day or 16.5 µg/kg bw/day. Applying a factor of 4, to allow for inter-human differences in toxicokinetics, leads to a TDI for perchlorate of 4 µg/kg bw/day.

Expression of ARE-binding proteins AUF1 and HuR in follicular adenoma and carcinoma of thyroid gland.

Both adenylate-uridylate rich elements binding proteins AUF1 and HuR may participate in thyroid carcinoma progression. In this study we investigated the expression of both factors on a protein level with a special focus on follicular adenoma and follicular thyroid carcinoma. By employment of immunofluorescence and western blot on 68 thyroid tissues including 7 goiter, 16 follicular adenoma (4 adenomatous hyperplasia), 19 follicular thyroid carcinomas, 13 papillary thyroid carcinomas and 14 undifferentiated thyroid carcinomas we investigated protein expression of AUF1 and HuR. In addition to previous results we demonstrated that AUF1 and HuR are significantly up-regulated in carcinoma tissues as compared with follicular adenoma or goiter tissues. Furthermore, by evaluation of AUF1 or HuR expression, or combination of both proteins on total tissue lysates, we were able to demonstrate a significant difference between follicular adenoma and follicular thyroid carcinoma. Overexpression of AUF1 and HuR is a common finding observed in thyroid malignancy. Analysis of the tissues obtained by surgical resection as demonstrated in this study is comparable to a fine needle aspiration and in combination with AUF1/HuR immuno-analysis may support the conventional immunohistological investigations. The promising results of this study were performed on relatively small collective, but justify future development of a quick thyroid diagnostic test on larger cohort of the patients, especially for thyroid samples which are inadequate for histological examinations.

IGF-1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH-stimulated goiter.

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in Wistar Hannover GALAS rats.

Outbred stocks of rats have been used extensively in biomedical, pharmaceutical and/or toxicological studies as a model of genetically heterogeneous human populations. One of such stocks is the Wistar Hannover GALAS rat. However, the colony of Wistar Hannover GALAS rat has been suspected of keeping a problematic mutation that manifests two distinct spontaneous abnormalities, goiter and dwarfism, which often confuses study results. We have successfully identified the responsible mutation, a guanine to thymine transversion at the acceptor site (3' end) of intron 6 in the thyroglobulin (Tg) gene (Tgc.749-1G>T), that induces a complete missing of exon 7 from the whole Tg transcript by mating experiments and subsequent molecular analyses. The following observations confirmed that Tgc.749-1G>T/Tgc.749-1G>T homozygotes manifested both dwarfism and goiter, while Tgc.749-1G>T/+ heterozygotes had only a goiter with normal appearance, suggesting that the mutant phenotypes inherit as an autosomal semi-dominant trait. The mutant phenotypes, goiter and dwarfism, mimicked those caused by typical endocrine disrupters attacking the thyroid. Hence a simple and reliable diagnostic methodology has been developed for genomic DNA-based genotyping of animals. The diagnostic methodology reported here would allow users of Wistar Hannover GALAS rats to evaluate their study results precisely by carefully interpreting the data obtained from Tgc.749-1G>T/+ heterozygotes having externally undetectable thyroidal lesions.

Expression of FoxP3 protein plays a key role in thyroid tumors in children.

The expression of FoxP3 in tumor cells might play an important role in cancer progression. We evaluated the immunoexpression of FoxP3 in thyroid tumors in children. Studies revealed high nuclear FoxP3 expression in follicular adenoma, papillary carcinoma, follicular carcinoma and low in goiter. Malignant tumors and adenomas, revealed a statistically significant higher expression of FoxP3 compared with the thyroid goiter. High FoxP3 expression in malignant lesions compared with low expression in goiter, may be indirect evidence of its role in carcinogenesis. Revealed high expression of FoxP3 in benign tumor, may suggest a strong activation of oncogenic processes in this lesion.

[Bilateral neck exploration with intraoperative iPTH assay in patients not eligible for minimally invasive parathyroidectomy]. / Obustronna eksploracja szyi ze sródoperacyjnym monitoringiem stezenia parathormonu u chorych niekwalifikujacych sie do maloinwazyjnej paratyreoidektomii.

BACKGROUND AND AIMS: Bilateral neck exploration (BNE) is the preferred surgical technique in patients with primary hyperparathyroidism (pHPT) not eligible for minimally invasive parathyroidectomy (MIP). The aim of this study was to assess indications for BNE in the era of MIP, including short-term outcomes of surgery with intraoperative intact parathyroid hormone (iPTH) monitoring added-value. METHODS: Data of 155 patients with pHPT qualified for BNE with intraoperative iPTH monitoring and treated in 2003-2012 were retrospectively analysed. All patients underwent biochemical and imaging testing in the preoperative work-up. The following endpoints were analysed in this study: indications for BNE, short-term outcomes of surgery, and intraoperative iPTH monitoring added-value. RESULTS: Indications for BNE were: negative preoperative imaging in 65 (41.9%) patients, concomitant goitre necessitating surgical removal in 51 (32.9%) patients, MEN 1 syndrome in 17 (11.0%) patients, lithium treatment in 12 (7.7%) patients, lacking consent for MIP in 5 (3.2%) patients, and MEN 2A syndrome in 5 (3.2%) patients. The extent of parathyroidectomy was a solitary parathyroid adenoma removal in 97 (62,6%) patients, subtotal parathyroidectomy in 41 (26.4%) patients, and double-parathyroid adenoma removal in 17 (11,0%) patients. Use of intraoperative iPTH monitoring influenced on the extent of parathyroid tissue resection in 16(10.3%) patients. Normalised total serum calcium values were observed in 154 (99.4%) patients during a 6-month follow-up. CONCLUSIONS: BNE in patients with pHPT is the preferred surgical technique in the following circumstances: a suspicion of multiglandular parathyroid disease (MEN 1 or 2A syndrome, familial hyperparathyroidism, lithium therapy), a negative preoperative imaging, in patients not consenting for MIP, and in cases with concomitant goitre necessitating surgical treatment. Use of intraoperative iPTH monitoring influences on the extent of parathyroid tissue resection in one often patients, hence assuring the highest quality of surgical treatment.

Immunophenotyping with high-dimensional flow cytometry identifies Treg cell subsets associated with recurrence in papillary thyroid carcinoma.

The activation of Treg cell subsets is critical for the prognosis of tumor patients; however, their heterogeneity and disease association in papillary thyroid carcinoma (PTC) need further investigation. We performed high-dimensional flow cytometry for immunophenotyping on thyroid tissues and matched peripheral blood samples from patients with multinodular goiters or PTC. We analyzed CD4+ T cell and Treg cell phenotypes and compared the recurrence-free survival of PTC patients with different Treg cell subset characteristics using TCGA. Furthermore, PTC recurrent and non-recurrent group were compared by multiplex immunohistochemistry. High-dimensional flow cytometry and bioinformatics analysis revealed an enrichment of Tregs in tumors compared with multinodular goiters and peripheral blood specimens. Moreover, effector Tregs (e-Tregs) as well as FOXP3+ non-Tregs were enriched in tumor samples, and the expression of CD39, PD-1, and CD103 increased on tumor Tregs. TCGA data analysis showed that individuals with CD39hi PD-1loCD103loe-Treghi and CD39loPD-1loCD103hie-Treghi expression patterns had a high recurrence rate. According to the multiplex immunohistochemistry and analysis, compared with non-recurrent group, the proportion of high recurrence rate effector Treg clusters (CD39+PD-1-CD103- plus CD39-PD-1-CD103+) was increased in recurrent patients. Overall, our results highlight the potential of e-Treg subsets as future immunotherapy targets for PTC recurrence.

The role of iodine in human growth and development.

Iodine is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. Iodine deficiency is a major public health problem; globally, it is estimated that two billion individuals have an insufficient iodine intake. Although goiter is the most visible sequelae of iodine deficiency, the major impact of hypothyroidism due to iodine deficiency is impaired neurodevelopment, particularly early in life. In the fetal brain, inadequate thyroid hormone impairs myelination, cell migration, differentiation and maturation. Moderate-to-severe iodine deficiency during pregnancy increases rates of spontaneous abortion, reduces birth weight, and increases infant mortality. Offspring of deficient mothers are at high risk for cognitive disability, with cretinism being the most severe manifestation. It remains unclear if development of the offspring is affected by mild maternal iodine deficiency. Moderate-to-severe iodine deficiency during childhood reduces somatic growth. Correction of mild-to-moderate iodine deficiency in primary school aged children improves cognitive and motor function. Iodine prophylaxis of deficient populations with periodic monitoring is an extremely cost effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle.

Detection and comparison of cut-off values for total AgNOR area/nuclear area and AgNOR number/nucleus in benign thyroid nodules and normal thyroid tissue.

Argyrophilic nucleolar organising region associated proteins (AgNORs) are of interest in a variety of diseases including thyroid disorders. We have investigated the cut-off values for AgNOR count and with a new approach, Total AgNOR area/nuclear area (TNORa/Na) proportions to discriminate thyrocytes obtained from benign thyroid nodules and normal thyroid tissue. Thirty patients whose fine needle aspiration (FNA) materials were compatible with a benign lesion (named as goiter group) and 30 controls (subjects with normal thyroid tissue) were included. In the control group, biopsy material was obtained from histologically normal thyroid gland operated on because FNA material was compatible with papillary thyroid carcinoma (PTC). These samples were stained for AgNOR and 100 nuclei per individual were examined. Both AgNOR values for individual cells and cut-off values were detected for each group. Patients with goiter had significantly (P<0.001) higher AgNOR count (2.1 ± 0.6%) and TNORa/Na (6.1 ± 1.5%) than the control groups (1.4 ± 0.2 and 3.0 ± 0.4, respectively). The cut-off values were <1.5 for AgNOR count and <3.8 for TNORa/Na in thyrocytes of the controls. This modified method is an easy and reliable method for discriminating various thyroid disorders, including the differentiation of benign thyroid nodules from malignant ones. It also helps to discriminate thyrocytes obtained from benign nodules from normal thyroid tissue, aiding accurate localisation of sampling in FNA material.

Coordinated expression of galectin-3 and caveolin-1 in thyroid cancer.

Galectin-3 (Gal3) is the single most accurate marker for the diagnosis of differentiated thyroid cancer (DTC). Gal3 overrides the tumour suppressor activity of caveolin-1 (Cav1) and functions in concert with Cav1 to promote focal adhesion turnover and tumour cell migration and invasion. To study their coordinated role in progression of a human cancer, we investigated the expression of Gal3 and Cav1 in specimens of human benign thyroid lesions, DTC and anaplastic thyroid cancer (ATC). Gal3 and Cav1 expression is significantly associated with DTC and ATC, but not benign nodules. Essentially all Cav1-positive DTC cancers express Gal3, supporting the synergistic activity of these two proteins in DTC progression. Similarly, coordinated elevated Gal3/Cav1 expression was observed in three DTC-derived cell lines (papillary TCP1 and KTC1 and follicular FTC133) but only one (ACT1) of five ATC-derived cell lines. Using siRNA knockdown, Gal3 and Cav1 were shown to be required for RhoA GTPase activation, stabilization of focal adhesion kinase (FAK; a measure of focal adhesion signalling and turnover) and increased migration of the DTC cell lines studied, but not the ATC cell lines, including ACT1, which expresses elevated levels of Gal3 and Cav1. Co-expression of Gal3 and Cav1 in the T238 anaplastic cell line stabilized FAK-GFP in focal adhesions. Gal3 and Cav1 therefore function synergistically to promote focal adhesion signalling, migration and progression of DTC.

[Hirsutism and multinodular goiter in a 40-year-old female watchmaker]. / Hirsutismus und Struma multinodosa bei einer 40-jährigen Uhrmacherin.

This article presents the case of a female patient with acromegaly caused by ectopic production of growth hormone-releasing hormone (GHRH) secretion. In the presence of typical clinical features of acromegaly but a lack of evidence for a pituitary adenoma the results of somatostatin receptor scintigraphy were indicative of a typical carcinoid of the lungs as the cause of the ectopic secretion of GHRH and the stimulation of pituitary gland growth hormone secretion resulting in acromegaly. Finally, the patient underwent curative surgical treatment.

The evolution of thyroid function with puberty.

OBJECTIVE: This study was planned to describe thyroid functional status in different stages of puberty. STUDY DESIGN: We collected data from five schools across different geographical zones of Delhi. All children who consented were evaluated for anthropometry, pubertal stage, goitre status, serum free T3 (FT3), free T4 (FT4), TSH, anti-TPO (thyroid peroxidase) antibodies and thyroid ultrasound. From this sample, a disease- and risk-free or 'reference population' was obtained by excluding those with history of thyroid disease or use of thyroid medications, family history of thyroid disease, goitre, hypoechogenicity or nodularity on ultrasound or positive antithyroid antibodies. RESULTS: The 'total population' comprised 3722 children; the 'reference population' comprised 2134 subjects. The mean, median, 3rd and 97th percentiles of serum FT3, FT4 and TSH for each stage of puberty were obtained. In both boys and girls, FT3 increased with entry into puberty and either stayed constant or declined marginally after stage 3 of puberty. In contrast, in both genders, FT4 decreased with entry into puberty and stayed relatively constant after stage 3 of puberty. TSH levels declined through puberty in boys, but remained largely unchanged in girls. An increased conversion of T4 to T3 is the possible explanation for this finding. CONCLUSIONS: This large community-based study in school-age children using strict exclusion criteria provides data of thyroid function in the various stages of puberty. There is no evidence of 'thyroidarche' during or preceding puberty.

Thyroid status two decades after salt iodization: country-wide data in school children from India.

OBJECTIVE: Country-wide evaluation of thyroid disorders in school children following two decades of universal salt iodization (USI) has not been carried out till date. This study was planned with aim to assess thyroid status of school children two decades after the launch of USI programme. DESIGN: Population survey. PATIENTS: We collected data from 25 schools in 19 cities across five different geographical zones of India. Those children who were evaluated for anthropometry, and goitre status by palpation formed 'total population'. Children who consented to give blood samples were defined as 'study population'. MEASUREMENTS: Serum free T3, free T4, TSH, anti-TPO antibody and thyroid ultrasound. RESULTS: A total of 38,961 children aged 5-15 years formed total population. Goitre rate was 15.5% while thyroid hypoechogenicity was found in 4404 (11.3%) children. In the study population (13,790 children), 2258 (16.4%) had goitre, 505 (3.7%) had positive anti-TPO antibody titres, 1001 (7.3%) had hypothyroidism (TSH > 5.2 µIU/ml) and 41 (0.3%) had thyrotoxicosis (TSH < 0.1 µIU/ml). Among goitrous children, 203 (9.0%) had anti-TPO positivity, 365 (16.1%) had hypoechogenicity of thyroid and either of these were present in 488 (21.6%) children. CONCLUSIONS: Endemic goitre in school children persisted nationwide, despite more than two decades of USI programme. Thyroid autoimmunity only partially explains the increase in goitre prevalence.