The Effect of Conventional Open Thyroidectomy on Clinical Results and Respiratory Function Tests in Multinodular Goitre.

AIM: The primary aim of our study was to measure the effect of conventional open thyroidectomy performed for patients with multinodular goiter (MNG) on pulmonary volumes measured with respiratory function tests independent from surgical indications. A secondary aim was to determine whether there was a significant improvement in the complaints due to obstructive symptoms after MNG surgeries. METHODS: This study was conducted between October 2020 and June 2022. Patients who were hospitalized to undergo surgery for giant multinodular goiter were prospectively included in the study. Patients were questioned about complaints of pressure, hoarseness, dyspnea, sleep apnea, snoring, and dysphagia before the surgery and during the follow-up 6 months after surgery. In addition, pulmonary function tests were performed preoperatively, 48 hours after surgery and 6 months after surgery. Forced expiratory volume in 0.5 seconds forced expiratory volume in 1 second and forced vital capacity values in pulmonary function test (PFT) measurements were recorded. RESULTS: A total of 55 patients, 42 females and 13 males, mean age 49.54 ± 13.6 years, were included in the study. Although there was a significant decrease in clinical symptoms caused by the thyroid volume within 6 months in patients who were operated for giant MNG there was no significant change in pulmonary function tests. There was a positive correlation between the thyroid volume and nodule weight in patients with MNG. CONCLUSIONS: Our results suggest that it is not necessary to follow up with patients without obstructive findings in preoperative pulmonary function tests with pulmonary function tests in the postoperative period.

Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.

PURPOSE: Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. METHODS: Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. RESULTS: About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. CONCLUSION: In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.

Cochlear implantation in patients with Pendred syndrome.

OBJECTIVE: To examine the outcomes of cochlear implantation in children with Pendred Syndrome. MATERIAL AND METHODS: A retrospective case series of nine pediatric patients with Pendred syndrome undergoing cochlear implantation at a tertiary academic medical center from 2003 to 2017. RESULTS: All patients were diagnosed with bilateral mild-to-profound to severe-to-profound sensorineural hearing loss and used hearing aids prior to implantation. Preoperative imaging results revealed that all patients exhibited bilateral enlarged vestibular aqueducts and 8 of 9 had cochlear dysplasia equivalent to Incomplete Partition II. Despite inner ear malformations, all electrodes were successfully implanted with minimal complications and favorable post-operative audiological outcomes. CONCLUSIONS: Cochlear implantation is an effective and successful treatment for severe-to-profound hearing loss in children with Pendred syndrome and for whom traditional amplification aids provide limited benefit. With early intervention, cochlear implantation allows speech and cognitive development in Pendred children comparable to that of normal hearing individuals, allowing patients to learn in a mainstream educational setting.

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment.

PURPOSE: Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). PATIENTS AND METHODS: Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. RESULTS: In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. CONCLUSIONS: Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease.

Thyroid gland changes in patients with acromegaly.

OBJECTIVE: Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. RESULTS: Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. CONCLUSIONS: Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.

ANALYSIS OF STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE THYROID GLAND IN PATIENTS WITH MALIGNANT BREAST TUMORS, WHO SUFFERED FROM THE CHORNOBYL ACCIDENT. / ANALIZ STRUKTURNYKh I FUNKTsIONAL'NYKh POKAZNYKIV ShchYTOPODIBNOÏ ZALOZY U PATsIIeNTIV ZI ZLOIaKISNYMY NOVOUTVORENNIaMY MOLOChNOÏ ZALOZY, IaKI POSTRAZhDALY VID AVARIÏ NA ChAES.

OBJECTIVE: Study the nature of structural and functional changes in the thyroid gland in patients with malignant tumors of the mammary glands that have suffered from the Chornobyl accident. MATERIALS AND METHODS: Examination of 80 patients with malignant tumors of the mammary glands at the age of 27-85 years. In 78 patients were diagnosed with breast cancer with different stages of the spread of the tumor process. The participants in the aftermath of the accident were 12 people, living in radioactive contaminated areas - 68. Mammography was performed with the help of mammographs Senographe 700 T and 800 Tsm. Echo- graphic study of the structure of the mammary gland and the thyroid gland was performed on the ultrasound devices Nemio XG SSA-580. Computed tomography was performed on a multi-detector computed tomography 64 КТ «LightSpeed VCT¼. MRI was performed on a magnetic resonance imager «Magnetom Vision Plus 1,5 T¼. For trepan biopsies, special needles were used in combination with a biopsy system gun «Magnum¼. The functional state of the thyroid gland was studied by studying the level of the thyroid hormone in peripheral venous blood. RESULTS: The results of the ultrasound study on the structural changes in the thyroid gland (TG) and markers that characterize the functional state of the TG in women with breast cancer, show that 60 out of 80 patients who asked for help with various forms of breast cancer and examined in the clinic, revealed the presence of structural changes in the thyroid gland, which is 75 %.Сonclusions. Structural changes in the thyroid gland in patients with breast cancer, who are considered victims of the Chornobyl Nuclear Power Plant accident, were diagnosed in 75 %, of which 71.25 % of patients did not know about the presence of pathological changes in the thyroid gland before the examination in the clinic. In the struc- ture of the identified pathological changes in the thyroid gland, 47.5 % accounted for the nodular goiter, 10 % for small hydrophilic and small fibrous areas, 3.75 % for previously undergone surgery for thyroid removal, 3.75 % for chronic thyroiditis, 7.5 % - CAIT, 2.5 % - cystic changes in the thyroid gland, 3.75 % - nodular goiter and CAIT.

Association between TSH Level and Pregnancy Outcomes in Euthyroid Women Undergoing IVF/ICSI: A Retrospective Study and Meta-analysis.

The aim of this study was to determine the association between thyroid-stimulating hormone (TSH) level and pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI). A total of 1185 women were enrolled in the retrospective study, and 12 studies with a total of 6624 women were included in the meta-analysis (including the data of the present retrospective study). Participants in the retrospective study were divided into two groups in terms of their serum TSH levels: TSH ≤2.5 mIU/L group (n=830) and TSH >2.5 mIU/L group (n=355). They were monitored for the status of clinical pregnancy or miscarriage. In the TSH ≤2.5 mIU/L group, 441 (53.1%) women achieved clinical pregnancy, while 48 (5.8%) had early pregnancy loss and 12 (1.4%) had ectopic pregnancy. In the TSH >2.5 mIU/L group, 175 (49.3%) women achieved clinical pregnancy, while 21 (5.9%) had early pregnancy loss and 3 (0.8%) had ectopic pregnancy. No significant differences were observed between the two groups in pregnancy outcomes (P=0.126, P=0.512, P=0.297). The meta-analysis also revealed no significant difference in the clinical pregnancy rate and the miscarriage rate between women with serum TSH ≤2.5 mIU/L and those with serum TSH >2.5 mIU/L. In conclusion, high TSH levels (TSH level >2.5 mIU/L) did not affect clinical pregnancy rate or increase miscarriage rate in euthyroid women undergoing IVF/ICSI.

A knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation.

SLC26A4 gene mutations lead to Pendred syndrome and non-syndromic hearing loss (DFNB4). The mouse model is well used to study the pathology of Pendred syndrome, however, mice with different Slc26a4 mutations exhibit different phenotypes, and these mice have severe deafness and inner ear malformations that are not imitated less severely Human phenotype. In this study, we generated a knock-in mouse model of Pendred syndrome with Slc26a4 L236P mutation to mimic the most common mutation found in human. Some L236P mice were observed to have significant vestibular dysfunction including torticollis and circling, the giant otoconia and destruction of the otoconial membrane was observed in L236P mice. Unlike other profoundly deafness in Slc26a4 mouse model, L236P mice present mild to profound hearing loss, consistent with the hearing threshold, inner ear hair cells also lost from slight to significant. Together, these data demonstrate that the L236P mouse phenotype is more similar to the human phenotype and should be used as a tool for further research into the human Pendred syndrome.

An assessment of the relationship between thyroid nodule characteristics, insulin resistance and arterial stiffness in euthyroid nodular goiter.

OBJECTIVES: Publications suggesting that thyroid nodule might be associated with insulin resistance and metabolic syndrome are quite interesting. There is a need for studies assessing the relationship between nodule presence and cardiovascular risk in individuals with non-functioning nodular goiter. The purpose of the present study is to reveal whether or not insulin resistance, nodule presence, and nodule stiffness affect arterial stiffness, which is a reliable and valid cardiovascular risk indicator, in individuals with euthyroid nodular goiter using the pulse wave analysis (PWA). MATERIALS AND METHODS: 50 patients with euthyroid nodular goiter and 50 healthy volunteers were included in the study. All participants were examined by B-mode thyroid ultrasound, and the participants in the nodular goiter group were also examined by strain elastography (SE). The strain index of nodules was calculated according to the Rago scoring. Also, fasting plasma glucose (FPG) and insulin levels were measured, and HOMA-IR. Arterial stiffness measurements of the participants were performed using a PWA device which employs a cuff-based oscillometric method from the brachial artery. RESULTS: PWV was found to be significantly higher in the euthyroid nodular goiter group (p < 0.001). PWV was found to be positively correlated with FPG and waist circumference. Fasting plasma glucose was found to be higher in the group with nodular goiter (p = 0.03). However, no difference was found between the groups in terms of HOMA-IR and insulin level. HOMA-IR was not correlated with thyroid volume, nodule volume, and nodule count. Also, HOMA-IR was not correlated with strain index value and PWA data. CONCLUSION: We found that PWV was significantly higher in patients with euthyroid nodular goiter. This result suggests that these patients may be at risk for cardiovascular disease.

Efecto combinado de la interacción genética sobre el desarrollo del bocio nodular con tiroiditis autoinmune y adenoma tiroideo en los habitantes de Bucovina del Norte / Combined effect of gene-gene interaction on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the inhabitants of Northern Bukovyna

ABSTRAC This article presents the results of a comprehensive analysis of the combined influence of genetic polymorphisms associated with various links of apoptosis regulation (BCL-2, CTLA-4 and APO-1/Fas) on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the studied population. The analysis was performed using the Multifactor Dimensionality Reduction (MDR) method by calculating the prediction potential. Graphic models of gene-gene interaction with the highest cross-validation consistency created by the MDR method showed complex "synergistic or independent" impact of polymorphic loci of the CTLA-4 (+49G/A), Fas (-1377G/A) and BCL-2 (63291411 A>G) genes on the onset of thyroid pathology in general, or its individual types (nodular goiter with autoimmune thyroiditis and thyroid adenoma) in the population of Northern Bukovyna.

RESUMEN Este artículo presenta los resultados de un análisis exhaustivo de la influencia combinada de polimorfismos genéticos asociados a diversos enlaces en la regulación de la apoptosis (BCL-2, CTLA-4 y APO-1/FAS) sobre el desarrollo de bocio nodular con tiroiditis autoinmune y adenoma tiroideo en la población estudiada. Para ello, se utilizó el método de reducción de dimensionalidad multifactorial (MDR) mediante el cálculo de los potenciales de predicción. Los modelos gráficos de interacción gen-gen con la mayor consistencia de validación cruzada creada por el método MDR mostraron un complejo impacto «sinérgico o independiente¼ de los loci polimórficos de los genes CTLA-4 (+49G/A), FAS (-1377G/A) y BCL-2 (63291411A>G) en el inicio de la patología tiroidea en general, o sus tipos individuales (bocio nodular con tiroiditis autoinmune y adenoma tiroideo) en la población de Bucovina septentrional.

The effect of Metformin treatment in obese insulin-resistant patients with euthyroid goiter.

Objective The study's objective was to evaluate the thyroid parameters in obese insulin-resistant patients with euthyroid diffuse or nodular goiter, following Metformin treatment. Patients and methods The study was experimental, open, and prospective. Fifty-three patients aged 18-68 were enrolled for two years. Obese insulin-resistant patients (cut-off Homeostasis-Model-Assessment of Insulin Resistance-HOMA-IR ≥ 2.5) with euthyroid nodular/diffuse goiter were included. Subjects with diabetes, hypo-/hyper-thyroidism, autoimmune thyroiditis, psychiatric disorders, liver or heart failure were excluded. Patients were randomly assigned to one of the following treatment: Metformin 1000 mg/day + Levothyroxine 25 µg/day (M + LT4 group) and only Levothyroxine 25 µg/day (LT4 group). Thyroid and metabolic parameters' evolution was investigated over six months. Results The two groups were comparable at baseline (p ≥ 0.10). TSH, waist/hip ratio (WHR), visceral fat thickness (VFT), insulin, and HOMA-IR decreased significantly more in M + LT4 group compared to LT4 group. TSH decrease correlated with WHR reduction (p = 0.002) only in M + LT4 group. Moreover, the multivariate regression analysis revealed that insulin's and HOMA-IR levels' decrease was an independent factor associated with FT4's increase (p = 0.031, p = 0.033) just in M + LT4 group. No other independent association between the evolution (Δ) of TSH, thyroid volume (TTV), thyroid nodules-maximum diameter (TN-MD), and metabolic parameters was found. In addition, no significant threshold between groups was reached when ΔFT4, ΔTTV, ΔTN-MD were compared (p > 0.07), although their significant improvement was recorded between the baseline and the follow-up moment in each group (p < 0.003). Conclusion Metformin added to obese insulin-resistant patients treated with Levothyroxine for diffuse/nodular goiter determined a significant decrease in TSH and metabolic parameters, compared to those treated with Levothyroxine alone, but no significant difference regarding thyroid morphology after 6 months.

Changes in Swallowing Symptoms and Esophageal Motility After Thyroid Surgery: A Prospective Cohort Study.

INTRODUCTION: Swallowing difficulties, the pathophysiology behind which is incompletely understood, have been reported in 47-83% of goiter patients referred for thyroidectomy. We aimed at examining the influence of thyroid surgery on swallowing symptoms and esophageal motility. METHODS: Thirty-three patients with benign nodular goiter undergoing thyroid surgery were included. All completed high-resolution esophageal manometry examinations and the goiter symptom scale score, assessed by the thyroid-specific patient-reported outcome measure. The evaluations were performed before and 6 months after surgery. RESULTS: Before surgery, the goiter symptom score was median 39 points (range 2-61), which improved to median five points (range 1-52) after surgery (p < 0.001). The motility parameters were within the limits of normal swallowing physiology, both before and after surgery. Only the upper esophageal sphincter (UES) pressure increased significantly from 70.6 ± 27.7 to 87.7 ± 43.2 mmHg after surgery (p = 0.04). Using regression analyses, there was no significant correlation between change in goiter symptoms and weight of the removed goiter, motility parameters, or motility disturbances. However, patients undergoing total thyroidectomy experienced a larger reduction in pressure in the area of the UES and former thyroid gland after surgery in comparison with patients undergoing less extensive surgery. CONCLUSIONS: Goiter symptoms improved significantly after thyroidectomy, but without correlation to esophageal motility disturbances. This information is essential when interpreting dysphagia in patients with nodular goiter, and when balancing patients' expectations to surgical goiter therapy. REGISTRATION NUMBER: NCT03100357 ( www.clinicaltrials.org ).

Pendred syndrome.

Pendred syndrome is an autosomal recessive disorder that is classically defined by the combination of sensorineural deafness/hearing impairment, goiter, and an abnormal organification of iodide with or without hypothyroidism. The hallmark of the syndrome is the impaired hearing, which is associated with inner ear malformations such as an enlarged vestibular aqueduct (EVA). The thyroid phenotype is variable and may be modified by the nutritional iodine intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4/PDS gene, which encodes the multifunctional anion exchanger pendrin. Pendrin has affinity for chloride, iodide, and bicarbonate, among other anions. In the inner ear, pendrin functions as a chloride/bicarbonate exchanger that is essential for maintaining the composition and the potential of the endolymph. In the thyroid, pendrin is expressed at the apical membrane of thyroid cells facing the follicular lumen. Functional studies have demonstrated that pendrin can mediate iodide efflux in heterologous cells. This, together with the thyroid phenotype observed in humans (goiter, impaired iodine organification) suggests that pendrin could be involved in iodide efflux into the lumen, one of the steps required for thyroid hormone synthesis. Iodide efflux can, however, also occur in the absence of pendrin suggesting that other exchangers or channels are involved. It has been suggested that Anoctamin 1 (ANO1/TMEM16A), a calcium-activated anion channel, which is also expressed at the apical membrane of thyrocytes, could participate in mediating apical efflux. In the kidney, pendrin is involved in bicarbonate secretion and chloride reabsorption. While there is no renal phenotype under basal conditions, severe metabolic alkalosis has been reported in Pendred syndrome patients exposed to an increased alkali load. This review provides an overview on the clinical spectrum of Pendred syndrome, the functional data on pendrin with a focus on its potential role in the thyroid, as well as the controversy surrounding the relative physiological roles of pendrin and anoctamin.

Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels / Estado de vitamina D en pacientes egipcios con BMN eutiroideo y su correlación con las concentraciones de TSH

Background and aim: Although the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals’ environment are likely. However, to the best of our knowledge, it remains unknown whether there is a relationship between vitamin D status and prevalence or pathogenesis of euthyroid MNG. Therefore, the goal of the present study was determination of vitamin D status in euthyroid MNG as well as exploration of the correlation between vitamin D status & TSH levels. Methods: A total of 77 patients diagnosed with euthyroid MNG and 50 subjects without goiter were matched according to age, weight and BMI as control group in this case control study. Results: We found that patients with euthyroid MNG had statistically significant lower mean of [25(OH)D] (24.21±8.68ng/mL) in comparison with its mean in control subjects (28.37±10.91ng/mL, P value=0.019). The 28 sufficient vitamin D MNG patients had statistically significant lower level of TSH than 49 insufficient vitamin D MNG patients. Vitamin D and TSH levels correlate with vitamin D levels in MNG patients in Pearson correlation. Also 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients in regression analysis. Conclusions: Patients with euthyroid MNG have lower levels of vitamin D and TSH levels correlate with vitamin D levels in euthyroid MNG patients. In addition, 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients. We recommend hypovitaminosis D evaluation and correction in patients with MNG (AU)

Antecedentes y objetivo: A pesar de su amplia prevalencia en todo el mundo, se sabe poco de la patogénesis del BMN. Es probable que existan interacciones complejas de la predisposición genética y el entorno de los sujetos. No obstante, sigue sin saberse si existe una relación entre el estado de vitamina D y la prevalencia o la patogénesis del BMN eutiroideo. Por ello, el objetivo de este estudio era determinar el estado de vitamina D en el BMN eutiroideo, y explorar la correlación entre las concentraciones de vitamina D y TSH. Métodos: En este estudio de casos y controles se emparejó por edad, peso e IMC a 77 pacientes diagnosticados BMN eutiroideo y a 50 sujetos sin bocio como grupo de control. Resultados: Los pacientes con BMN eutiroideo tenían una concentración media de (25[OH]D) (24,21±8,68ng/ml) significativamente inferior a la hallada en los sujetos de control (28,37±10,91ng/ml, valor de p=0,019). Los 28 pacientes con BMN y vitamina D suficiente tenían valores de TSH estadísticamente inferiores a los 49 pacientes con BMN y vitamina D insuficiente. Las concentraciones de vitamina D y de TSH se correlacionan con los valores de vitamina D en los pacientes con BMN en la correlación de Pearson, y la 25 OH vitamina D era un factor predictivo independiente de los valores de TSH en los pacientes con BMN eutiroideo en un análisis de regresión. Conclusiones: Los pacientes con BMN eutiroideo tienen concentraciones más bajas de vitamina D y los valores de TSH se correlacionan con los de vitamina D en esos pacientes. Además, la 25 OH vitamina D era un factor predictivo independiente importante de la concentración de TSH en los pacientes con BMN eutiroideo. Se recomienda la evaluación de la hipovitaminosis D y su corrección en los pacientes con BMN (AU)

[The clinical definition and etiology of Pendred syndrome (a review of the literature and clinical observations)]. / Sindrom Pendreda (obzor literatury i klinicheskie nablyudeniya).

The aim of this work was a clinical study of the patients with mutations in the SLC26A4 gene and clinical diagnosis of the Pendred syndrome. The Pendred syndrome is a hereditary autosomal recessive disorder characterized by combined pathology of the inner ear and the thyroid gland. CT of the temporal bones demonstrates the Mondini-type structural anomaly in the inner ear and enlarged vestibular aqueduct. Examination of the thyroid gland reveals hypothyroidism and euthyroid goiter. A total of 20 unrelated children at the age from 2 to 16 years presenting with the hearing loss of different severity were available for the examination. High-resolution CT of the temporal bones demonstrated abnormal development of the inner ear including the Mondini-type structural anomaly and enlarged vestibular aqueduct. Five children with congenital hypothyroidism suffered from bilateral sensorineural impairment of hearing. The routine methods of audiological and molecular genetic examination were used throughout the study. RESULTS: As a result of molecular genetic studies, four out of the 20 patients were found to carry six recessive mutations of the SLC26A4 gene in the compound heterozygous and one such gene in the homozygous state which confirmed the hereditary nature of the disease. The children suffered the hearing loss of varying severity diagnosed at different age. The thyroid hypofunction in one child was identified when it was 2 years of age, and in two children at the age of 8 and 9 years. CONCLUSION: The first step in the diagnosis of the Pendred syndrome among children with congenital hearing loss was a CT scan of the temporal bones that showed incomplete separation of the curls of the cochlea and enlarged vestibular aqueduct. It is necessary to continue to study epidemiology, clinical and molecular genetics of the Pendred syndrome in the Russian population.

Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease.

BACKGROUND: To reduce intraoperative and postoperative complications, using Lugol solution to preoperatively prepare patients with Graves' disease has (1) rapidly reduced the severity of thyrotoxicosis and (2) reduced the vascularity of the thyroid gland. The vascularity reduction normally accompanies reducing the severity of thyrotoxicosis. However, the effects and mechanism of Lugol solution for reducing blood flow have not been well investigated in the patients with euthyroid (normally functioning thyroid) Graves' disease. METHODS: Twenty-five patients with euthyroid Graves' disease being preoperatively treated with Lugol solution for 10 days were measured, at baseline and on the operative day, for (1) superior thyroid artery blood flow; (2) systemic angiogenic factor (VEGF); and (3) systemic inflammatory factor [interleukin (IL)-16]. RESULTS: All three parameters were significantly (p < 0.0001) lower after 10 days of Lugol solution treatment. The average reductions were blood flow: 60% (0.294 vs. 0.117 L/min), serum VEGF: 55% (169.8 vs. 76.7 pg/mL), and serum IL-16: 50% (427.2 vs. 214.2; pg/mL). CONCLUSION: Lugol solution significantly reduced thyroid arterial blood flow, VEGF, and IL-16, even in patients with euthyroid Graves' disease. We recommend routine preoperative Lugol solution treatment for all patients with Graves' disease.

Thymosin beta 10 correlates with lymph node metastases of papillary thyroid carcinoma.

BACKGROUND: Thymosin beta 10 (TMSB10) has recently been recognized as being an important player in the metastatic cascade including tumor angiogenesis, invasion, and metastasis. However, a role for this protein in papillary thyroid carcinoma (PTC) has not yet been established. METHODS: Real-time polymerase chain reaction was used to examine the expression of TMSB10 messenger RNA in 36 cases of thyroid tissue samples: normal thyroid, PTC without lymph node metastases (LNM) and PTC with LNM (n = 12 cases in each subgroup). For immunohistochemistry, 130 patients with PTC were selected during the period of 2004-2005, 91 with and 39 without LNM. Statistical analysis was applied to evaluate the correlation between TMSB10 expression and LNM of PTC. RESULTS: By real-time polymerase chain reaction analysis, the expression of TMSB10 messenger RNA in normal thyroid tissue, PTC without LNM, and PTC with LNM tissue were significantly different (P < 0.0001). On immunohistochemistry analysis of 130 patients with PTC, in which 91 cases had cervical LNM and 69 cases had central neck LNM, high expression levels for TMSB10 were more common in patients with cervical LNM compared with patients without (81% versus 33%, P < 0.001). Similarly, high expression levels of TMSB10 were more common in patients with central neck LNM compared with those without (87.0% versus 44.3%, P < 0.001). CONCLUSIONS: High expression levels of TMSB10 correlated with LNM in PTC, especially in the central neck region. Patients with PTC with low levels of TMSB10 expression may be unlikely to have central neck LNM and could therefore avoid prophylactic central neck dissection.

A 4-MicroRNA signature can discriminate primary lymphomas from anaplastic carcinomas in thyroid cytology smears.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) and primary thyroid lymphoma (PTL) are uncommon tumors of the thyroid gland with several overlapping clinical and pathologic features that may render their differentiation difficult in fine-needle aspiration (FNA) cytology. MicroRNA (miRNA) signatures have been recently reported as useful diagnostic tools applied to cytology specimens. METHODS: Smears of 23 ATCs, 14 PTLs, and 20 non-neoplastic materials with multinodular goiter (MNG) were retrieved and classified based on their cytologic features and flow cytometric profiles. The ATC-related expression of hsa-miR-26a, hsa-miR-146b, hsa-miR-221, and hsa-miR-222 was quantified using quantitative reverse transcriptase-polymerase chain reaction analysis. RESULTS: All miRNAs were remarkably up-regulated in ATC samples compared with PTL samples (P < .01). Moreover, expression levels of hsa-miR-146b, hsa-miR-221, and hsa-miR-222 were significantly higher in ATCs than in MNG samples (P < .01). Significant down-regulation of hsa-miR-26a was observed in PTLs compared with MNG samples, whereas hsa-miR-146b was overexpressed. Receiver operating characteristic analysis was used to determine the optimal cutoff for distinguishing ATC from PTL. The estimated receiver operating characteristic thresholds displayed a sensitivity level greater than 0.80 in achieving a diagnosis of PTL, allowing the correct identification of 13 of 14 PTL samples (93%). CONCLUSIONS: Histotype-specific miRNA signatures can provide new insight into the molecular mechanisms of thyroid carcinogenesis. The tested 4-miRNA signature is a promising diagnostic tool for differentiating ATC from PTL and non-neoplastic MNG, even in the presence of scant material obtained from minimally invasive procedures.