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Journal Cover European Thyroid Journal
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     ISSN (Print) 2235-0640 - ISSN (Online) 2235-0802
     Published by Karger Homepage  [104 journals]
  • Anaplastic Carcinoma and Toxic Multinodular Goiter: An Unusual
           Presentation
    • Abstract: A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far.
      Eur Thyroid J
       
  • Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and
           Simultaneous Cushing's Syndrome
    • Abstract: Background: Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. Case Report: A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. Conclusion: We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.
      Eur Thyroid J
       
  • Novel NKX2-1 Frameshift Mutations in
           Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome
    • Abstract: Objectives: To verify the involvement of NKX2-1 gene in infants with brain-lung-thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset. Methods: The candidates were selected by a case-finding approach in 130 CH and 53 IMH infants. The NKX2-1 gene was analyzed by direct sequencing and multiplex ligation-dependent probe amplification. The variants were studied in vitro, by expression analyses and luciferase bioassay. Results: Four cases (3 CH and 1 IMH) consistent with BLT syndrome were identified. Two children were affected with respiratory distress and CH, but wild-type NKX2-1 gene. The remaining two presented choreic movements and no pulmonary involvement, but discrepant thyroid phenotypes: one had severe CH with lingual ectopy and the other one IMH with gland in situ. They were carriers of new de novo heterozygous frameshift mutations of NKX2-1 (c.177delG and c.153_166del14). The c.177delG leads to a prematurely truncated protein (p.H60TfsX11) with undetectable activity in vitro. The c.153_166del14 leads to the generation of an elongated aberrant protein (p.A52RfsX351) able to translocate into the nucleus, but completely inactive on a responsive promoter. Conclusions: Two novel heterozygous frameshift mutations of NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype among 183 hypothyroid infants. The atypical hypothyroid phenotypes of these 2 children (CH with lingual ectopy or IMH of postnatal onset) further expand the clinical spectrum that can be associated with NKX2-1 mutations. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
  • CBX7 Expression in Oncocytic Thyroid Neoplastic Lesions (Hürthle Cell
           Adenomas and Carcinomas)
    • Abstract: Background: Previous analysis of CBX7 expression in a large number of thyroid adenoma and carcinoma samples revealed a progressive reduction of CBX7 levels that was well related with the malignant grade of thyroid neoplasias. Hürthle cell tumors are unusual thyroid neoplasms characterized by the presence of particular cells called oncocytes. Objectives: In order to develop new tools for a more accurate diagnosis of Hürthle cell tumors of the thyroid, we evaluated CBX7 protein levels to verify the possible presence of an expression signature. Methods: CBX7 expression was evaluated by immunohistochemistry in a panel of thyroid tissue sections including normal thyroids, goiters, follicular adenomas and oncocytic lesions. Results: CBX7 expression was low or null in 68% of Hürthle adenomas, whereas it was comparable to normal thyroid tissue in Hürthle hyperplasias and follicular adenomas. Conclusions: Reduced expression of CBX7 suggests a more aggressive identity of Hürthle adenomas with respect to non-Hürthle ones. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
  • A Conservative Approach Is Reasonable in Patients with Non-Toxic Goitre:
           Results from an Observational Study during 30 Years
    • Abstract: Background: There is a lack of consensus in Europe regarding the management of patients with benign goitre. The object of this study was to find out the long-term results of recommending to patients with clinically and cytologically benign non-toxic goitres not to be operated. Methods: 980 patients were initially referred for surgical evaluation due to non-toxic goitre, 508 of whom underwent directly thyroidectomy. The remaining 473 patients (median age 56 years) were not operated and followed prospectively for a median period of 145 months. Results: During follow-up, 38% of the 473 patients were re-referred to the surgeon for a new evaluation due to different complaints, mainly growth of the goitre and/or worsening of local symptoms. 102 of the 473 patients (22%) had surgery and 27 (5.7%) developed thyrotoxicosis. 14 patients (3%) were diagnosed with thyroid carcinoma, 4 (0.46%) of whom (all elderly women) died of the disease. Conclusions: In patients with non-toxic goitre in whom surgery is not deemed necessary at initial evaluation, a conservative approach is reasonable. There is, however, a small risk for the development of aggressive carcinomas, and a fourth of the patients are operated at a median follow-up of 12 years. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
  • Patient Knowledge of Antithyroid Drug-Induced Agranulocytosis
    • Abstract: Background: Agranulocytosis is a serious side effect of antithyroid drugs. Objective: To ascertain the knowledge of patients and review the quality of information available on the internet. Methods: A questionnaire survey was performed for patients receiving antithyroid drugs. Patients attending endocrine clinics who were receiving antithyroid drug treatment (group A, n = 33) were interviewed. A further national cohort of patients (group B, n = 100) treated with antithyroid drugs, participated in an online survey. Results: 60.9% of responders were not aware of the common symptoms of agranulocytosis. 18.6% had never received any information about side effects. Of the 108 patients who recalled receiving information, 30% rated the quality as ‘poor' or ‘not good at all'. Structured interviews of group A patients revealed that almost half (45.5%, 15/33) had experienced symptoms that could be indicative of agranulocytosis, but only 53.3% (8/15) had a blood count checked. A review of 20 selected patient information internet sites revealed a significant variation in advice given to patients. Conclusions: Inadequate knowledge about agranulocytosis among patients receiving antithyroid drug treatment is common. The available information on the internet is variable and inconsistent. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
  • Population Reference Values and Prevalence Rates following Universal
           Screening for Subclinical Hypothyroidism during Pregnancy of an
           Afro-Caribbean Cohort
    • Abstract: Background: Subclinical hypothyroidism (SCH) has been reported to be associated with adverse pregnancy outcomes, however universal screening and treatment is controversial. Objectives: Our objectives were to determine population-specific pregnancy reference values (R1) for serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) at 14 weeks' gestation, along with the prevalence of SCH and thyroid peroxidase antibody (TPOAb). Methods: This was a prospective hospital-based cohort study. 1,402 subjects were recruited. Blood samples were obtained from 769 singleton pregnancies due to default between recruitment and scheduled blood draw. The prevalence of SCH was determined using R1, the laboratory non-pregnant reference values (R2) and previously recommended pregnancy reference values (R3). Results: R1 for TSH and FT4 was 0.03-3.17 mU/l (mean ± SD, 1.1 ± 0.76) and 8.85-17.02 pmol/l (mean ± SD, 11.96 ± 2.06), respectively. The prevalence of SCH using reference values R1, R2 and R3 was 1.4% (11/769), 0.5% (4/769) and 1.9% (15/769). Prevalence was significantly greater using R3 when compared to R2 (p = 0.011). TPOAb prevalence was 2.6%. A significantly greater prevalence of TPOAb was found in subclinical hypothyroid subjects using all three reference values than in euthyroid subjects (∼25 vs. 2%, p < 0.05). Conclusions: These reference values are the first to be reported for an Afro-Caribbean population. Our findings support the use of pregnancy-specific reference values in our population. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
  • Structure and Function of Thyroid Hormone Plasma Membrane Transporters
    • Abstract: Thyroid hormones (TH) cross the plasma membrane with the help of transporter proteins. As charged amino acid derivatives, TH cannot simply diffuse across a lipid bilayer membrane, despite their notorious hydrophobicity. The identification of monocarboxylate transporter 8 (MCT8, SLC16A2) as a specific and very active TH transporter paved the way to the finding that mutations in the MCT8 gene cause a syndrome of psychomotor retardation in humans. The purpose of this review is to introduce the current model of transmembrane transport and highlight the diversity of TH transmembrane transporters. The interactions of TH with plasma transfer proteins, T3 receptors, and deiodinase are summarized. It is shown that proteins may bind TH owing to their hydrophobic character in hydrophobic cavities and/or by specific polar interaction with the phenolic hydroxyl, the aminopropionic acid moiety, and by weak polar interactions with the iodine atoms. These findings are compared with our understanding of how TH transporters interact with substrate. The presumed effects of mutations in MCT8 on protein folding and transport function are explained in light of the available homology model. © 2014 European Thyroid Association Published by S. Karger AG, Basel

       
  • Thyroid Incidentalomas: Epidemiology, Risk Stratification with Ultrasound
           and Workup
    • Abstract: A thyroid incidentaloma is an unexpected, asymptomatic thyroid tumor fortuitously discovered during the investigation of an unrelated condition. The prevalence rate is 67% with ultrasonography (US) imaging, 15% with computed tomography (CT) or magnetic resonance imaging (MRI) of the neck, and 1-2% with fluorodeoxyglucose (FDG) positron emission tomography. In the absence of a history of external beam radiation or familial medullary thyroid cancer, the risk of malignancy ranges between 5 and 13% when discovered with US, CT or MRI, but is much higher if based on focal FDG uptake (30%). All patients with a thyroid incidentaloma, independent of the mode of detection, should undergo a dedicated neck US with risk stratification: US imaging allows a quantitative risk stratification of malignancy in thyroid nodules, named ‘reporting system' or ‘TIRADS' (thyroid imaging reporting and data system). The reported sensitivity ranges from 87 to 95% for the detection of carcinomas and the negative predictive value from 88 to 99.8%. We suggest that the indications for fine-needle aspiration be based mainly on size and US risk stratification. However, the diagnosis and workup of thyroid incidentalomas leads to superfluous surgery for benign conditions, and excess diagnosis and treatment of papillary microcarcinomas, the vast majority of which would cause no harm. Recognizing this must form the basis of any decision as to supplementary investigations and whether to offer therapy, in a close dialogue between patient and physician. The current use of minimally invasive nonsurgical ablation options, as alternatives to surgery, is highlighted. © 2014 European Thyroid Association Published by S. Karger AG, Basel

       
  • Anxiety and Depression Are More Prevalent in Patients with Graves' Disease
           than in Patients with Nodular Goitre
    • Abstract: Background and Objective: Graves' disease has been associated with an increased psychiatric morbidity. It is unclarified whether this relates to Graves' disease or chronic disease per se. The aim of our study was to estimate the prevalence of anxiety and depression symptoms in patients with Graves' disease compared to patients with another chronic thyroid disease, nodular goitre, and to investigate determinants of anxiety and depression in Graves' disease. Methods: 157 cross-sectionally sampled patients with Graves' disease, 17 newly diagnosed, 140 treated, and 251 controls with nodular goitre completed the Hospital Anxiety and Depression Scale (HADS). The differences in the mean HADS scores between the groups were analysed using multiple linear regression, controlling for socio-demographic variables. HADS scores were also analysed dichotomized: a score >10 indicating probable ‘anxiety'/probable ‘depression'. Determinants of anxiety and depression symptoms in Graves' disease were examined using multiple linear regression. Results: In Graves' disease levels of anxiety (p = 0.008) and depression (p = 0.014) were significantly higher than in controls. The prevalence of depression was 10% in Graves' disease versus 4% in nodular goitre (p = 0.038), anxiety was 18 versus 13% (p = 0.131). Symptoms of anxiety (p = 0.04) and depression (p = 0.01) increased with comorbidity. Anxiety symptoms increased with duration of Graves' disease (p = 0.04). Neither thyroid function nor autoantibody levels were associated with anxiety and depression symptoms. Conclusions: Anxiety and depression symptoms were more severe in Graves' disease than in nodular goitre. Symptoms were positively correlated to comorbidity and duration of Graves' disease but neither to thyroid function nor thyroid autoimmunity. © 2014 European Thyroid Association Published by S. Karger AG, Basel
      Eur Thyroid J
       
 
 
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