Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Ectopic intrapulmonary thyroid masquerading as metastatic carcinoma of the lung: a rare case scenario.

BACKGROUND: The intrapulmonary ectopic thyroid gland is exceedingly rare since the ectopic thyroid was discovered. Only eight cases have been reported in the worldwide literature. We present a case of multiple intrapulmonary ectopic thyroid glands with nodular goiter in a 10-year-old girl. CASE PRESENTATION: The girl was found with multiple intrapulmonary nodules in bilateral lungs during the treatment of nodular goiter. The intrapulmonary lesions were initially thought to be a high possibility of metastatic cancer. A computed tomography-guided percutaneous lung biopsy was performed, and the pathological examination confirmed that the diagnosis was ectopic intrapulmonary thyroid. CONCLUSION: The ectopic intrapulmonary thyroid should be considered when children with nodular goiter presenting with suspected metastases in the lung.

[Surgical treatment of a patient with stage v multinodular toxic goiter, severe thyrotoxicosis, strangulation syndrome and severe comorbidities]. / Khirurgicheskoe lechenie patsientki s mnogouzlovym toksicheskim zobom V stepeni, tireotoksikozom tyazheloi stepeni, kompressionnym sindromom i tyazhelymi soputstvuyushchimi zabolevaniyami.

The authors describe thyroidectomy in a patient with multinodular toxic goiter stage V, severe thyrotoxicosis complicated by thyro-cardiac disease, strangulation syndrome and severe comorbidities. Nodular euthyroid goiter was first diagnosed in 1992, and resection of the right thyroid lobe was performed. Progressive enlargement of thyroid gland and thyrotoxicosis occurred after coronavirus infection in February, 2020. Along with progression of thyrotoxicosis and strangulation of cervical organs, the patient suffered from portal vein thrombosis, pulmonary embolism. Myeloproliferative disease with essential thrombocythemia was also diagnosed. Volume of the right and left thyroid lobes was 69 and 101.3 cm3, respectively. X-ray examination of the esophagus revealed narrowing at C6 level up to 5-8 mm. Surgery time was 2 hours, dimension of removed right thyroid lobe - 10.0×7.5×6.5 cm, left thyroid lobe - 11.0×6.5×5.5 cm, total weight - 348 g. The patient was discharged in 6 days after surgery.

Congenital chloride diarrhea and Pendred syndrome: case report of siblings with two rare recessive disorders of SLC26 family genes.

BACKGROUND: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder causes severe dehydration and electrolyte disturbances. Homozygous variants in the nearby gene SLC26A4 disrupt anion exchange in the inner ear and the thyroid, causing Pendred syndrome (PDS; OMIM 274600), which is the most frequent form of syndromic deafness. CASE PRESENTATION: We report an unusual co-occurrence of two rare homozygous mutations in both the SLC26A3 and SLC26A4 genes, causing a rare combination of both CLD and PDS in two siblings. Although the clinical pictures were typical, the combined loss of these anion transporters might modulate the risk of renal injury associated with CLD. CONCLUSIONS: Familial presentation of two rare autosomal recessive disorders with loss of function of different SLC26 anion transporters is described. Independent homozygous variants in the SLC26A3 and SLC26A4 genes cause CLD and PDS in siblings, shedding light on co-occurrence of rare recessive traits in the progeny of consanguineous couples.

Low level of plasma fibulin-1 in patients with thyroid lesions: a case-control study and literature review.

Investigating novel biomarkers discriminating thyroid nodules is a matter of great importance for differential diagnosis. The current study was planned to investigate the diagnostic value of fibulin-1 in plasma specimens of patients with thyroid nodules. A literature review was also performed to gain an understanding of the existing research relevant to the main role of fibulin-1 in carcinogenesis. In this case-control study, the levels of plasma fibulin-1 were compared in 82 subjects including papillary thyroid cancer (PTC; n = 30), multinodular goiter (MNG; n = 30), and healthy subjects (n = 22) using enzyme-linked immunosorbent assay (ELISA). Fibulin-1 levels of patients with PTC and MNG were documented to be significantly lower than those of healthy subjects (PTC vs. Healthy; P = 0.000, MNG vs. Healthy; P = 0.000). No statistically significant differences were found between PTC and MNG groups when fibulin-1 levels were compared (P > 0.05). Low level of plasma fibulin-1 was associated with an increased risk of PTC tumorigenesis (odds ratio = 0.810; 95% CI: 0.704-0.933; P = 0.003). Further, fibulin-1 had an appropriate diagnostic value for detecting PTC patients with a sensitivity of 73.33%, and specificity of 100% at the cutoff value > 4.9 (ng/ml). According to the results of the present research which are tied well with previous studies, the abnormal downregulation of fibulin-1 may play a role in the PTC and MNG tumorigenesis. In addition, fibulin-1 probably promotes the development and progression of other human cancer; however, further studies are needed to improve current understandings.

Genetic interaction analysis of VEGF-A rs3025039 and VEGFR-2 rs2071559 identifies a genetic profile at higher risk to develop nodular goiter.

CONTEXT: Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. OBJECTIVE: The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development. PATIENTS AND METHODS: 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy-Weinberg equilibrium was performed. RESULTS: None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development. CONCLUSIONS: Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

Clinical impact of a cytological screening system using cyclin D1 immunostaining and genomic analysis for the diagnosis of thyroid nodules.

BACKGROUND: Fine-needle aspiration (FNA) is the most reliable method for diagnosing thyroid nodules; however, some features such as atypia of undetermined significance or follicular lesion of undetermined significance can confound efforts to identify malignancies. Similar to BRAF, cyclin D1 may be a strong marker of cell proliferation. METHODS: One hundred two patients with thyroidal nodule were enrolled in this prospective study. Expression of cyclin D1 in thyroid nodules was determined by immunohistochemistry using both surgical specimens and their cytological specimens. The identification of the optimal cut off points for the diagnosis of malignancy were evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) of markers were evaluated from crosstabs based on cut off points and significance were calculated. We also analyzed genetic variants by target NGS for thyroid nodule samples. RESULTS: The positive predictive value (PPV) and median stain ratio (MSR) of cyclin D1 nuclear staining was determined in papillary thyroid carcinoma (PPV = 91.5%, MSR = 48.5%), follicular adenoma (PPV = 66.7%, MSR = 13.1%), and adenomatous goiter and inflammation controls (MSR = 3.4%). In FNA samples, a threshold of 46% of immunolabelled cells allows to discriminate malignant lesions from benign ones (P < 0.0001), with 81% sensitivity and 100% specificity. A 46% cutoff value for positive cyclin D1 immunostaining in thyroid cells demonstrated 81% sensitivity and 100% specificity. In surgical specimens, ROC curve analysis showed a 5.8% cyclin D1 immunostaining score predicted thyroid neoplasms at 94.4% sensitivity and 92.3% specificity (P = 0.003), while a 15.7% score predicted malignancy at 86.4% sensitivity and 80.5% specificity (P < 0.0001). Finally, three tested clinico-pathological variables (extra thyroidal extension, intraglandular metastasis, and lymph node metastasis) were significant predictors of cyclin D1 immunostaining (P < 0.001). CONCLUSION: Our cytological cyclin D1 screening system provides a simple, accurate, and convenient diagnostic method in precision medicine enabling ready determination of personalized treatment strategies for patients by next generation sequencing using cytological sample.

Comparison of a Bridge Immunoassay with Two Bioassays for Thyrotropin Receptor Antibody Detection and Differentiation.

A rapid and fully automated chemiluminescent immunoassay for the detection of thyrotropin receptor autoantibodies (TSHR-Ab) based on a bridge technology was compared with two bioassays that measure either stimulating (TSAb) or blocking (TBAb) antibodies for the detection and differentiation of TSHR-Ab. A total of 229 patients with various thyroid disorders [151 with Graves' disease (GD), 35 with Hashimoto's thyroiditis (HT), 32 with nodular goiter, and 11 with thyroid cancer] were included. The bridge immunoassay was performed according to the manufacturer's instructions (cut-off>0.55 IU/l). TSAb and TBAb were measured with reporter bioassays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off>34% inhibition). TSAb was reported as percentage of specimen-to-reference ratio (> 140 SRR%). The 3 TSHR-Ab assays were negative in all patients with benign euthyroid nodular goiter and differentiated thyroid cancer. In contrast, in all patients with GD, irrespective of the disease duration, TSHR-Ab positivity was present in 127 of 151 (84%) and 140 (93%) for the bridge assay and TSAb bioassay, respectively (p<0.001). Fifteen of 151 (10%) GD samples were positive in the TSAb bioassay but negative in the bridge assay. The bridge assay and the TSAb bioassay correlated positively (r=0.39, p<0.0001) in patients with GD. Both assays detected TSHR-Ab in all ten untreated hyperthyroid patients with GD. In GD patients with a duration of less than six months, 27/29 (93%) and 28 (97%) were TSHR-Ab positive with the bridge and TSAb bioassay, respectively. In comparison, TSHR-Ab were present in two of 35 (6%) and five (14%) HT patients with the bridge and TSAb bio-assay, respectively. TSHR blocking antibodies were present in one (3%) patient with HT and in two (1%) patients with GD; these two GD patients were also bridge assay positive but TSAb bioassay negative. In conclusion, the bridge immunoassay and both bioassays are highly sensitive for the detection of TSHR-Ab. The bridge assay is, however, also positive in the presence of TSHR blocking antibodies detected in a TBAb bioassay.

A comparison of haemogram parameters of patients with thyroid papillary cancer and nodular goiter in Van, Turkey.

OBJECTIVE: To compare the haemogram parameters of patients with thyroid papillary cancer and nodular goiter. METHODS: The retrospective comparative study was conducted at Van Training and Research Regional Hospital, Van, Turkey, and comprised data of patients who underwent thyroidectomy from 2011 to 2015. The data was compared between patients with papillary thyroid cancer (group 1) and those with nodular hyperplasia (group 2) in terms of age, gender and thyroid stimulating hormone level as well as haemogram parameters, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. SPSS 20 was used for statistical analysis. RESULTS: Of the 90 patients, 53(59%) were in group 1 with papillary thyroid cancer and 37(%) in group 2 with nodular hyperplasia. Platelet-lymphocyte ratio was significantly higher in group 1 (p=0.015). Mean platelet volume was significantly higher in group 1 patients with a diameter of 1cm or more (p<0.05). Within group 1, lymphocyte count was significantly high in patients with invasion (p<0.05). In correlation analysis, group 1 patients with a tumour diameter of 1cm or more showed a significant correlation in mean platelet volume, tumour multicentricity, lymphocyte count, vascular invasion, thyroglobulin, platelet distribution width, platelet number and tumour multicentricity (p<0.05). CONCLUSION: Only platelet-lymphocyte ratio could assist in distinguishing benign goiter from thyroid cancer. Also, mean platelet volume, lymphocyte count, and platelet distribution width appeared to be effective prognostic markers for papillary thyroid cancer.

A Case of Marine-Lenhart Syndrome with Predominance of Plummer Disease.

A 74-year-old woman with a left neck mass and thyrotoxicosis was referred to our hospital, and was later diagnosed with Marine-Lenhart syndrome based on positivity for thyroid autoantibodies, ultrasonographically evident left lobe thyroid nodule with increased blood flow, and scintigraphically identified not only increased tumor-like accumulation but also diffused uptake. Disease control was difficult despite administration of antithyroid drugs, so subtotal thyroidectomy was performed. No hyperplastic changes or histopathological findings characteristic of Graves disease were evident on histopathology, so Plummer disease was considered to be dominant. In case of hot in low type which showed higher uptake in the nodule and lower uptake in the extranodular part on scintigraphy, there is a possibility of relapse in drug treatment.

131I-Induced Graves' disease in patients treated for toxic multinodular goitre: systematic review and descriptive analysis.

BACKGROUND: Graves' disease (GD) arising after the treatment of toxic multinodular goitre (TMNG) with radioiodine has long been described but it remained unclear whether GD was in fact iodine induced, its incidence, risk factors, natural history and treatment outcomes. METHODS: A systematic search using The Cochrane Library, Medline and PubMed Central allowed the pooling of data from 3633 patients with thyroid autonomy, 1340 patients with TMNG, to fill gaps in knowledge, regarding the clinical expression of iodine-induced GD (131I-IGD) in adults. RESULTS: 131I-IGD developed in 0-5.3% of those with thyroid autonomy (first year) and in 5-5.4% of those with TMNG, 3-6 months after treatment. Patients with toxic adenoma were less affected. 131I-IGD was more common in patients with pre-treatment direct or indirect signs of autoimmunity: positive anti-TPO (p < 0.05), glandular hypoechogenicity, TRAbs within reference range, diffuse uptake on 99mTc-pertechnetate scans (p < 0.05), findings that may increase the risk tenfold. 131I-IGD manifested 3 months after 131I, justifying 15.4-29% of cases of relapse. The rate of spontaneous remission was 17-20% (6 months) and the rate of relapse after a second 131I treatment 22-25%. The use of an uptake-based administered 131I activity led to a greater proportion of euthyroid patients (78% compared to 25-50% with the mass-based approach). CONCLUSIONS: GD may be triggered by 131I. The incidence of the condition is low. Several risk factors were consistently identified; some have shown to raise the risk significantly. 131I-IGD seems more treatment resistant than iodine-independent GD and the best resolution rates were achieved with uptake-based selected iodine activities.

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

AIM: Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. METHODS: We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. RESULTS: No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. CONCLUSIONS: White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Computer-aided diagnosis of malignant or benign thyroid nodes based on ultrasound images.

The objective of this study is to evaluate the diagnostic value of combination of artificial neural networks (ANN) and support vector machine (SVM)-based CAD systems in differentiating malignant from benign thyroid nodes with gray-scale ultrasound images. Two morphological and 65 texture features extracted from regions of interest in 610 2D-ultrasound thyroid node images from 543 patients (207 malignant, 403 benign) were used to develop the ANN and SVM models. Tenfold cross validation evaluated their performance; the best models showed accuracy of 99% for ANN and 100% for SVM. From 50 thyroid node ultrasound images from 45 prospectively enrolled patients, the ANN model showed sensitivity, specificity, positive and negative predictive values, Youden index, and accuracy of 88.24, 90.91, 83.33, 93.75, 79.14, and 90.00%, respectively, the SVM model 76.47, 90.91, 81.25, 88.24, 67.38, and 86.00%, respectively, and in combination 100.00, 87.88, 80.95, 100.00, 87.88, and 92.00%, respectively. Both ANN and SVM had high value in classifying thyroid nodes. In combination, the sensitivity increased but specificity decreased. This combination might provide a second opinion for radiologists dealing with difficult to diagnose thyroid node ultrasound images.

[Results of molecular genetic testing in Russian patients with Pendred syndrome and allelic disorders].

Pendred syndrome is an autosomal recessive inherited disorder characterized by a combination of sensorineural hearing impairment and euthyroid goiter; its clinical manifestation in children is hardly distinguishable from nonsyndromic hearing loss. Pendred syndrome is one of the most frequent types of syndromic hearing loss. Hearing impairment is accompanied by abnormal development of the bony labyrinth­enlarged vestibular aqueduct (EVA) and occasionally combined with Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin protein, are responsible for both Pendred syndrome and for allelic disorder (nonsyndromic enlarged vestibular aqueduct). The present study for the first time conducted molecular genetic analysis in 20 Russian patients with Pendred syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in the SLC26A4 gene were revealed in four patients. The mutation c.222G>T (p.Trp74Cys) was detected for the first time. Mutations were found in patients with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia. Mutations were not detected in patients with isolated Mondini dysplasia. One proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG mutation in the GJB2 gene. The absence of frequent mutations, including well-known ones or "hot" exons in the SLC26A4 gene, was reported. Therefore, the optimal method to search for mutations in the SLC26A4 gene in Russian patients is Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene.

Clinical presentation of hyperthyroidism in a large representative sample of outpatients in France: relationships with age, aetiology and hormonal parameters.

OBJECTIVE: Signs and symptoms of thyrotoxicosis are not specific, and thyroid function tests are frequently prescribed to recognize such thyroid dysfunction. Ultrasensitive assays of thyroid-stimulating hormone (TSH) allow early diagnosis and identification of mild hyperthyroidism (generally designed as 'subclinical'). The aim of this study was to re-evaluate the clinical picture of thyrotoxicosis in the context of the current large utilization of ultrasensitive TSH assays. DESIGN: Prospective descriptive cohort. METHODS: Clinical presentation of 1572 patients with a recent (<3 months) diagnosis of thyrotoxicosis recruited by a large representative sample of 263 French endocrinologists was studied using two questionnaires (one at inclusion and the second after 3 months) concerning symptoms, hormonal evaluation and treatment. RESULTS: A total of 1240 (78·9%) patients were women, mean age 48 ± 17 years. Subclinical hyperthyroidism (SCHT) was present in 86 patients (10·4%). Symptoms of thyrotoxicosis were in decreasing frequency order: palpitations, weakness, heat-related signs and disturbed sleep. A total of 64·9% of patients had lost weight. Signs and symptoms were more frequent in Graves' disease, in young patients, and were partially related to biochemical severity. Symptoms were less frequent in elderly patients except for cardiac manifestations (atrial fibrillation). Most patients with SCHT had one or several signs or symptoms of thyrotoxicosis. CONCLUSION: This study confirms that elderly patients have less symptoms of thyrotoxicosis than younger subjects but are at increased risk of cardiac complications. Our results show that most patients with 'subclinical' HT have in fact signs or symptoms of thyrotoxicosis.

Fine needle aspiration cytology of 650 thyroid nodules operated for multinodular goiter: a cyto-histological correlation based on the new Italian cytological classification (siapec 2014).

The new Italian cytological classification (SIAPEC 2014) of thyroid nodules, in line with those of Bethesda and BTA-RCPath, replaces the previous TIR3 class with two new classes (TIR3A and TIR3B), which correspond to different risks of malignancy and clinical actions required. The present study was conducted to evaluate the diagnostic accuracy of the new SIAPEC classification as opposed to its previous version (SIAPEC 2007). Preoperative cytology was compared with the final histology obtained from 650 consecutive patients who underwent total thyroidectomy for multinodular goiter. Of this total, 434 patients (group A) had their cytological diagnosis based on the old SIAPEC 2007 classification and 216 patients (group B) had their cytological diagnosis based on the SIAPEC 2014 classification. In group A 111 patients (25.6%) had a TIR3 diagnosis, while in group B 52 patients (24.1%) received a TIR3 diagnosis, of whom 30 had TIR3A and 22 had TIR3B. In group A, 46 (41.4%) out of the 111 patients with TIR3 diagnosis had, based on histology, a thyroid carcinoma. In group B, only 2 (6.7%) out of 30 patients with TIR3A diagnosis had a thyroid carcinoma. This rate of malignancy was significantly lower (p less than 0.001) than that observed in patients with TIR3B diagnosis, in which 12 (54.5%) out of 22 patients had a carcinoma. The observations here reported show that, in respect to the previous version, the new Italian cytological classification provides greater diagnostic accuracy for detecting thyroid nodule malignancy.

Pendred Syndrome in a Newborn with Neck Swelling: A Case Report.

BACKGROUND: Pendred syndrome is a rare autosomal recessive condition, characterized by functional impairment of thyroid gland and sensorineural hearing loss. The syndrome presents in patients with homozygous or compound heterozygous mutation. The presentation in the form of neck mass in a newborn is rare. CASE CHARACTERISTICS: A 1 month old baby presented to us with neck mass, which was found to be an enlarged thyroid gland. Thyroid function tests were consistent with hypothyroidism. Further evaluation revealed moderate sensorineural hearing loss; genetic analysis showed that baby was homozygous for the known mutations causing the disease. INTERVENTION: Thyroid hormone replacement and hearing habilitation were done. Follow up showed regression of the neck mass and normalization of thyroid function tests. Genetic counseling of the family was done. MESSAGE: Identification of the exact cause of congenital hypothyroidism can prevent grave consequences later on for the patient as well as for the family.

Comparative Evaluation of ß-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules.

We compared the results of gene molecular and immunocytochemical studies of ß-catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/ß-catenin complex leading to switching from adhesion function of ß-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-ß-catenin interactions in the mechanisms of malignant transformation of follicular epithelium.

Clinical Features and Surgical Treatment of Thyroid Pathology in Patients Over 65 Years.

INTRODUCTION: The significant increase in the average lifespan of the general population lead to a proportional enhacement in the prevalence of benign and malignant thyroid conditions and equally the number of surgeries for this pathology. PATIENTS AND METHOD: In a personal series of 464 thyroid disorders undergoing surgery over a two decades period we registered 51 patients (10.9%) aged over 65 years of which 11 (2.4%) having over 75 years. Demographic, clinical and diagnostic characteristics of these cases were analysed together with indications, management practice and outcome. Retrospective statistical analysis reaearching risk factor and confidence interval has not identified factors predicting higher risk of complication in this age group. RESULTS: There have been recorded 33 females and 18 males (R1=1,8/1) with clinically, laboratory and histologically confirmed diagnosis of 24 (multi)nodular goiters (47.0%), 18 thyrotoxicosis (35.2%) and also 9 (17.6%) thyroid carcinomas. Thirty-four total or near total thyroidectomies and 17 conservative exeresis were performed. There were not postoperative deaths but we recorded three cases of prolonged hypocalcemia, and two cases each of recurrent laryngeal nerve paresis and recurrences. In all benign cases we obtained a stable in time cure while in carcinomas survivals of 3-5 years were obtained in only 4 papillary tumors. CONCLUSIONS: Despite some difficulties in diagnostic and additional risks related to comorbidity benign and malignant pathology installed in patients over 65 years, may benefit of all types of conservative or radical thyroidectomies in terms of strict monitoring individualized in each case.

[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.