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Journal Cover   European Thyroid Journal
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   Full-text available via subscription Subscription journal
   ISSN (Print) 2235-0640 - ISSN (Online) 2235-0802
   Published by Karger Homepage  [103 journals]
  • Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease
    • Abstract: Background: Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Objective: Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Methods: Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level
       
  • Radioiodine Treatment and Thyroid Hormone Suppression Therapy for
           Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward
           Less Aggressive Treatment for Low-Risk Patients
    • Abstract: Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine.
      Eur Thyroid J 2015;4:82-92
       
  • Incidence and Significance of Incidental Focal Thyroid Uptake on 18F-FDG
           PET Study in a Large Patient Cohort: Retrospective Single-Centre
           Experience in the United Kingdom
    • Abstract: Objective: To assess the prevalence and pathological nature of incidental focal thyroid uptake on 18F-FDG (2-[18F]-fluoro-2-deoxy-D-glucose) PET (positron emission tomography) and examine the role of the maximum standardised uptake value (SUVmax) to differentiate benign from malignant thyroid pathology. Material and Methods: 18F-FDG PET reports were retrospectively reviewed. Incidental focal tracer uptake in the thyroid was noted in 147 patients (0.5%). Patients with known primary thyroid malignancy were excluded. The final diagnosis was made following ultrasonography of the neck, fine-needle aspiration cytology (FNAC) or histopathology of the surgically resected specimen where surgery was indicated. A Mann-Whitney U test was used to compare the SUVmax of benign and malignant thyroid pathology. Receiver operating characteristic (ROC) analysis was performed to identify an SUVmax cutoff in differentiating benign from malignant pathology. Results: A final diagnosis was achieved in 47/147 (32%) of the patients. The diagnoses included benign lesions in 36 patients and malignancy in 9 patients. In 2 patients, FNAC demonstrated indeterminate follicular lesions; however, surgical excision was not performed. There was a highly significant difference in the mean SUVmax of malignant focal thyroid uptake (15.7 ± 5.9) compared to that of benign lesions (7.1 ± 6.8) with a p value of 0.000123. An SUVmax of 9.1 achieved a sensitivity of 81.6%, specificity of 100% and area under the curve of 0.915 in the ROC analysis differentiating benign from malignant disease. Conclusion: The malignancy potential of incidental focal thyroid uptake remains high and warrants prompt and appropriate follow-up by the clinician. The SUVmax may aid in further characterisation of the lesion and its management.
      Eur Thyroid J
       
  • Assessment of the Effect of Two Distinct Restricted Iodine Diet Durations
           on Urinary Iodine Levels (Collected over 24 h or as a Single-Spot Urinary
           Sample) and Na+/I- Symporter Expression
    • Abstract: Introduction: A restricted iodine diet (RID) may be recommended for depletion of the whole-body iodine pool in patients with differentiated thyroid cancer referred for radioiodine treatment or a whole-body scan. Evaluation of the iodine pool is possible through urinary iodide (UI) measurements, which can be collected in 24-hour (24U) or spot urinary (sU) samples. However, the minimum period required for an RID to lower the iodine pool, the measurement of iodine in sU samples as a iodine pool marker, and the influence of the iodine pool on Na+/I- symporter (NIS) expression are debatable in the literature. Objectives: To compare the effects of 15- and 30-day RID on UI measurements in 24U and sU samples and the impact of RID on NIS expression. Methods: Thyroidectomized patients went on a 15- or 30-day RID and collected 24U and sU samples before and after the RID. Twenty healthy individuals were evaluated for mRNA NIS expression before and after the RID. Results: Of 306 patients, only 125 properly complied with both the RID and 24U collection. We observed a correlation between sU and 24U UI before the RID (n = 306, #x03C1; = 0.47, p < 0.001), after a 15-day RID (n = 79, #x03C1; = 0.49, p < 0.001), and after a 30-day RID (n = 46, #x03C1; = 0.73, p < 0.001). There was a significant decrease in UI after the RID. The median UI measurement was 275 μg/l at baseline and 99 and 80 μg/l after a 15- and 30-day RID, respectively. There was a significant increase in NIS expression after a 15-day RID. Conclusions: A 15-day RID is sufficient to deplete the iodine pool. sU can replace 24U UI as a marker for assessing the iodine pool. NIS expression was increased after a 15-day RID.
      Eur Thyroid J
       
  • Evaluation of Thyroid Bed Nodules on Ultrasonography after Total
           Thyroidectomy: Risk for Loco-Regional Recurrence of Thyroid Cancer
    • Abstract: Objectives: We conducted a retrospective chart review of patients with differentiated thyroid cancer who underwent total thyroidectomy to examine the correlation of the persistence of thyroid bed nodules seen on ultrasonography with subsequent loco-regional recurrence. Methods: A total of 60 patients with differentiated thyroid cancer were identified who underwent total thyroidectomy, received 131I therapy and had thyroid bed nodules on postoperative surveillance ultrasonography. The ultrasonographic features of the thyroid bed nodules and their progression over time along with serum thyroglobulin (Tg) levels were monitored. Those patients who demonstrated no evidence of recurrence were compared to patients who had recurrence. Results: Of the 60 patients, 25% had documented cancer recurrence. Sixty percent of the patients in the recurrence group had an increase in the size of bed nodules as compared to only 7% of the patients in the group without recurrence. An increase in serum Tg of more than 2-fold was seen in 80% of the patients with recurrence and in only 13% (6/45) of the patients without cancer recurrence. The odds of identifying recurrent thyroid cancer in patients with more than a 2-fold increase in serum Tg were 80.5 greater than in patients with a less than 2-fold increase in serum Tg. The odds of identifying recurrent thyroid cancer in patients with the presence of any suspicious thyroid bed nodule were 31.5 times greater than in patients without suspicious thyroid bed nodules. Conclusions: Thyroid bed nodules on surveillance ultrasound warrant fine-needle aspiration cytology if they increase in size and number, are persistent and associated with suspicious sonographic features.
      Eur Thyroid J 2015;4:106-114
       
  • Trace Amine-Associated Receptor 1 Localization at the Apical Plasma
           Membrane Domain of Fisher Rat Thyroid Epithelial Cells is Confined to
           Cilia
    • Abstract: Background: The trace amine-associated receptor 1 (Taar1) is one member of the Taar family of G-protein coupled receptors (GPCR) accepting various biogenic amines as ligands. It has been proposed that Taar1 mediates rapid, membrane-initiated effects of thyronamines, the endogenous decarboxylated and deiodinated relatives of the classical thyroid hormones T4 and T3. Objectives: Although the physiological actions of thyronamines in general and 3-iodothyronamine (T1AM) in particular are incompletely understood, studies published to date suggest that synthetic T1AM-activated Taar1 signaling antagonizes thyromimetic effects exerted by T3. However, the location of Taar1 is currently unknown. Methods: To fill this gap in knowledge we employed immunofluorescence microscopy and a polyclonal antibody to detect Taar1 protein expression in thyroid tissue from Fisher rats, wild type and taar1-deficient mice, and in the polarized FRT cells. Results: With this approach we found Taar1 is expressed in the membranes of sub-cellular compartments of the secretory pathway and on the apical plasma membrane of FRT cells. Three-dimensional analyses further revealed Taar1 immunoreactivity in cilial extensions of post-confluent FRT cell cultures that had formed follicle-like structures. Conclusions: The results suggest Taar1 transport along the secretory pathway and its accumulation in the primary cilium of thyrocytes. These findings are of significance, considering the increasing interest in the role of cilia in harboring functional GPCR. We hypothesize that thyronamines can reach and activate Taar1 in thyroid follicular epithelia by acting from within the thyroid follicle lumen, their potential site of synthesis, as part of a non-classical mechanism of thyroid auto-regulation.
      Eur Thyroid J
       
  • Sex-Dependent Claudin-1 Expression in Liver of Eu- and Hypothyroid Mice
    • Abstract: Background: In liver the tight junction protein claudin-1 plays an important role in bile secretion by maintaining the paracellular barrier of bile canaliculi and bile duct. A diminished bile excretion has been found in hypothyroid patients and the prevalence of gallstones is increased in hypothyroidism. This association however only applies for men and is in contrast to the well-established female preponderance of biliary disease in the general population. Objectives: We hypothesized that hypothyroidism could lead to altered claudin-1 expression in the liver and that this effect may be sex-specific. Methods: We characterized claudin-1 expression and localization in liver of euthyroid and hypothyroid male and female C57BL/6NTac mice by real-time PCR, Western blot and immunofluorescence. Results: Claudin-1 is expressed in canalicular regions and the bile ducts of murine liver. Livers of female mice showed lower claudin-1 expression than male livers. In hypothyroid mice livers, female animals showed an elevated claudin-1 expression whereas reduced claudin-1 expression was found in male animals compared to the euthyroid controls. Conclusion: We demonstrate a correlation between claudin-1 expression and hypothyroidism in murine liver. Furthermore, a sex-dependent alteration of claudin-1 expression was found.
      Eur Thyroid J
       
  • Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based
           Morphometry Study
    • Abstract: Background: Hyper- as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. Objectives: This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. Methods: High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Results: Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Conclusions: Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structure of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.
      Eur Thyroid J
       
  • High-Resolution Melting Is a Sensitive, Cost-Effective, Time-Saving
           Technique for BRAF V600E Detection in Thyroid FNAB Washing Liquid: A
           Prospective Cohort Study
    • Abstract: Objective: The diagnostic accuracy of thyroid fine needle aspiration biopsy (FNAB) can be improved by the combination of cytological and molecular analysis. In this study, washing liquids of FNAB (wFNAB) were tested for the BRAF V600E mutation, using the sensitive and cost-effective technique called high-resolution melting (HRM). The aim was to demonstrate the feasibility of BRAF analysis in wFNAB and its diagnostic utility, combined with cytology. Design: Prospective cohort study. Methods: 481 patients, corresponding to 648 FNAB samples, were subjected to both cytological (on cells smeared onto a glass slide) and molecular analysis (on fluids obtained washing the FNAB needle with 1 ml of saline) of the same aspiration. BRAF V600E analysis was performed by HRM after methodological validation for application to wFNAB (technique sensitivity: 5.4%). Results: The cytological results of the FNAB were: 136 (21%) nondiagnostic (THY1); 415 (64%) benign (THY2); 80 (12.4%) indeterminate (THY3); 9 (1.4%) suspicious for malignancy (THY4); 8 (1.2%) diagnostic of malignancy (THY5). The BRAF V600E mutation was found in 5 THY2, 2 THY3, 6 THY4 and 6 THY5 samples. Papillary carcinoma diagnosis was histologically confirmed in all BRAF+ thyroidectomized patients. BRAF combined with cytology improved the diagnostic value compared to cytology alone in a subgroup of 74 operated patients. Conclusions: HRM was demonstrated to be a feasible method for BRAF analysis in wFNAB. Thanks to its sensitivity and cost-effectiveness, it might be routinely used on a large scale in clinical practice. In perspective, standby wFNAB samples could be analyzed a posteriori in case of indeterminate cytology and/or suspicious findings on ultrasound.
      Eur Thyroid J
       
  • Prevalence of Cancer in Patients with Thyroid Nodules in the Island of
           Cyprus: Predictive Value of Ultrasound Features and Thyroid Autoimmune
           Status
    • Abstract: Background: The purpose of this study was to determine the prevalence of thyroid carcinoma in patients who underwent ultrasound-guided fine needle aspiration biopsy (USgFNA) of thyroid nodules in the island of Cyprus. Ultrasound features as well as the presence of autoimmune thyroid disease were evaluated as risk factors for malignancy. Methods: 322 consecutively examined patients (272 females/50 males, age 13-81) underwent USgFNA of thyroid nodules in a referral endocrine clinic between July 2007 and July 2009. The ultrasonographic characteristics examined were: echogenicity, margin irregularity, composition, calcifications, presence of increased vasculature and nodule size. The presence or absence of autoimmune thyroid disease was recorded. Results: From the 548 nodules examined, 74 (13.6%) were classified as THY3, 4 or 5. 75 patients (123 nodules) underwent surgical resection. 46 patients (64 nodules) proved to have thyroid carcinoma by histology. There was a significant correlation of suspicious/malignant cytology with solid composition, hypoechogenicity, irregular margins and the presence of calcifications. A significant association was also noted between the presence of positive antithyroglobulin antibodies (p < 0.05) and Graves' disease (p = 0.01) with suspicious/malignant cytology. Conclusion: The overall prevalence of thyroid cancer was 14.3%. Ultrasound characteristics were highly predictive of thyroid malignancy. Thyroid autoimmunity should be considered as a risk factor.
      Eur Thyroid J
       
 
 
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