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Journal Cover European Thyroid Journal
  [SJR: 0.38]   [H-I: 2]   [0 followers]  Follow
   Full-text available via subscription Subscription journal
   ISSN (Print) 2235-0640 - ISSN (Online) 2235-0802
   Published by Karger Homepage  [105 journals]
  • European Thyroid Association Guidelines regarding Thyroid Nodule Molecular
           Fine-Needle Aspiration Cytology Diagnostics
    • Abstract: Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.
      Eur Thyroid J 2017;6:115–129
  • Thyroid Autoimmunity and Thyroid Cancer: Review Focused on Cytological
    • Abstract: The association between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) has been originally suggested by retrospective pathological studies and has recently been re-evaluated and proposed on the basis of several fine-needle aspiration cytology (FNAC) studies. In FNAC studies, the association between HT and PTC is based on the comparison of anti-thyroid autoantibodies (ATA) (anti-thyroperoxidase [TPOAb] and anti-thyroglobulin [TgAb]), thyroid function (TSH), and cytology with histology of thyroid nodules and lymphocytic thyroid infiltration (LTI) of operated thyroid glands. Most of the pathological studies found a high prevalence rate of PTC in HT. In most FNAC studies, the risk ratio of PTC in HT patients was evaluated using multivariate statistical analysis: increased TSH levels represented the main and common independent risk factor of malignancy, although it resulted not consistently related to HT. On the other hand, several studies provided a positive relationship between ATA and PTC, particularly with TgAb. Two recent FNAC studies from the same referral center clearly demonstrated an independent risk for thyroid malignancy conferred by both TPOAb and TgAb, confirming the role of increased TSH levels, and found a significant association between PTC and ATA and diffuse LTI at histology. These studies are consistent with the hypothesis that autoimmune thyroid inflammation and increased serum TSH concentration may be involved in thyroid tumor growth. The complex relationship between HT and PTC, which involves immunological/hormonal pathogenic links, needs to be further investigated with prospective studies.
      Eur Thyroid J
  • Prolonged Duration of Surgery Predicts Postoperative Hypoparathyroidism
           among Patients Undergoing Total Thyroidectomy in a Tertiary Referral
    • Abstract: Background: Postoperative hypoparathyroidism is a common complication following total thyroidectomy. The aim of this study was to investigate the incidence of both transient and permanent hypoparathyroidism in patients undergoing total thyroidectomy in a tertiary referral centre and, furthermore, to identify early predictive risk factors. Methods: Based on a single-institution retrospective review, we identified 582 patients who underwent total thyroidectomy between January 2010 and March 2015. Information on age, gender, pathological diagnosis, duration of surgery, autotransplantation of parathyroid glands, neck dissection, and experience and position of the surgeon was retrieved from the medical records. Furthermore, serum levels of parathyroid hormone and calcium were registered pre- and postoperatively and after 3 and 12 months. Results: The incidence of transient hypoparathyroidism during the first 24 h and 3 months after surgery was 47.8 and 17.8%, respectively. Furthermore, the incidence of permanent hypoparathyroidism 1 year after surgery was 10.7%. A prolonged duration of surgery was significantly associated with hypoparathyroidism. Moreover, autotransplantation of parathyroid glands was a significant predictor of transient hypoparathyroidism after 24 h and 3 months, but was not associated with permanent hypoparathyroidism. Conclusions: Transient and permanent hypoparathyroidism is common among patients undergoing total thyroidectomy in a tertiary referral centre. A duration of surgery #x3e;120 min constitutes an independent risk factor due to the risk of ischaemic damage. Regain of function of devascularized parathyroid glands must be expected to last at least 1 year postoperatively. Furthermore, the recovery of autotransplanted parathyroid glands should not be evaluated within 1–3 months after surgery.
      Eur Thyroid J
  • Hypothyroid Patients Encoding Combined MCT10 and DIO2 Gene Polymorphisms
           May Prefer L-T3 + L-T4 Combination Treatment – Data Using a Blind,
           Randomized, Clinical Study
    • Abstract: Objectives: In previous studies, around half of all hypothyroid patients preferred levo-thyroxine (L-T4) + levo-triiodothyronine (L-T3) combination therapy, 25% preferred T4, and 25% had no preference. The reason for this is yet to be explored. Methods: A total of 45 overtly autoimmune, hypothyroid patients – now euthyroid on ≥6 months’ L-T4 therapy – participated in a prospective, double-blind, cross-over study. The patients were randomized into 2 groups of either 3 continuous months’ L-T4 therapy followed by 3 months’ combination therapy or vice versa. In all periods, 50 μg L-T4 was blindly replaced by either (identical) 50 μg L-T4 or by 20 μg T3. L-T4 was hereafter adjusted to obtain normal serum TSH values. We investigated 3 single nucleotide polymorphisms (SNPs) on the type II iodothyronine deiodinase (DIO2) gene (rs225014 (Thr92Ala), rs225015, and rs12885300 (ORFa-Gly3Asp)) and 1 SNP on the cellular membrane transport-facilitating monocarboxylate transporter (MCT10) gene (rs17606253), and asked in which of the 2 treatment periods patients felt better (i.e., which treatment was preferred). Results: 27 out of 45 patients (60%) preferred the combination therapy. Two polymorphisms (rs225014 (DIO2, Thr92Ala) and rs17606253 (MCT10)) were combined yielding 3 groups: none vs. 1 of 2 vs. both SNPs present, and 42 vs. 63 vs. 100% of our patients in the 3 groups preferred the combined treatment (Jongheere-Terpstra trend test, p = 0.009). Conclusion: The present study indicates that the combination of polymorphisms in DIO2 (rs225014) and MCT10 (rs17606253) enhances hypothyroid patients’ preference for L-T4 + L-T3 replacement therapy. In the future, combination therapy may be restricted or may be even recommended to individuals harbouring certain polymorphisms.
      Eur Thyroid J
  • Cardiac Thyroid Hormone Metabolism and Heart Failure
    • Abstract: The heart is a principal target of thyroid hormone, and a reduction of cardiac thyroid hormone signaling is thought to play a role in pathological ventricular remodeling and the development of heart failure. Studies in various rodent models of heart disease have identified increased activity of cardiac type III deiodinase as a possible cause of diminished levels and action of thyroid hormone. Recent data indicate novel mechanisms underlying the induction of this thyroid hormone-degrading enzyme in the heart as well as post-transcriptional regulation of its expression by microRNAs. In addition, the relevance of diminished thyroid hormone signaling for cardiac remodeling is suggested to include miRNA-mediated effects on pathological signaling pathways. These and other recent studies are reviewed and discussed in the context of other processes and factors that have been implicated in the reduction of cardiac thyroid hormone signaling in heart failure.
      Eur Thyroid J
  • Serum miRNAs as Biomarkers for the Diagnosis and Prognosis of Thyroid
           Cancer: A Comprehensive Review of the Literature
    • Abstract: Background/Objectives: Thyroid cancer is the most common endocrine malignancy and accounts for 1% of cancers. In recent years, there has been much interest in the feasibility of using miRNAs or miRNA panels as biomarkers for the diagnosis of thyroid cancer. miRNAs are noncoding RNAs with 21–23 nucleotides that are highly conserved during evolution. They have been proposed as regulators of gene expression, apoptosis, cancer, and cell growth and differentiation. Methods: The Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science were searched. Results: The serum level of miRNAs (miRNA-375, 34a, 145b, 221, 222, 155, Let-7, 181b) can be used as molecular markers for the diagnosis and prognosis of thyroid cancer in the serum samples of patients with thyroid glands. Conclusions: Given that most common methods for the screening of thyroid cancer cannot detect the disease in its early stages, identifying miRNAs that are released in the bloodstream during the gradual progression of the disease is considered a key method in the early diagnosis of thyroid cancers.
      Eur Thyroid J
  • TPOAb and Thyroid Function Are Not Associated with Breast Cancer Outcome:
           Evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant
           Chemotherapy Trial (TACT, CRUK01/001)
    • Abstract: Background: Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives: We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Methods: TACT women #x3e;18 years old with node-positive or high-risk node-negative early breast cancer (pT1–3a, pN0–1, M0), with stored plasma (n = 1,974), taken 15.5 (median; IQR 7.0–24.0) months after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1,745/1,974; 88.4%), hormonal therapy (1,378/ 1,974; 69.8%), or trastuzumab (48/1,974; 2.4%). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), and time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results: No difference in DFS was found by TPOAb status (unadjusted hazard ratio [HR]: 0.97, 95%CI: 0.78–1.19; p = 0.75) and/or thyroid function (unadjusted HR [hypothyroid vs. euthyroid]: 1.15, 95% CI: 0.79–1.68; p = 0.46; unadjusted HR [hyperthyroid vs. euthyroid]: 1.14, 95% CI: 0.82–1.61; p = 0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered, and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions: No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-to-high-risk early breast cancer was found in the largest and longest observational study to date.
      Eur Thyroid J
  • Radioiodine Ablation following Thyroidectomy for Differentiated Thyroid
           Cancer: Literature Review of Utility, Dose, and Toxicity

    • Abstract: Management recommendations for differentiated thyroid cancer are evolving. Total thyroidectomy is the backbone of curative-intent therapy, with radioiodine ablation (RAI) of the thyroid remnant routinely performed, in order to facilitate serologic surveillance and reduce recurrence risk. Several single-institution series have identified patient subsets for whom recurrence risk is sufficiently low that RAI may not be indicated. Further, the appropriate dose of RAI specific to variable clinicopathologic presentations remains poorly defined. While recent randomized trials demonstrated equivalent thyroid remnant ablation rates between low- and high-dose RAI, long-term oncologic endpoints remain unreported. While RAI may be employed to facilitate surveillance following total thyroidectomy, cancer recurrence risk reduction is not demonstrated in favorable-risk patients with tumor size ≤1 cm without high-risk pathologic features. When RAI is indicated, in patients without macroscopic residual disease or metastasis, the evidence suggests that the rate of successful remnant ablation following total thyroidectomy is equivalent between doses of 30–50 mCi and doses ≥100 mCi, with fewer acute side effects; however, in the setting of subtotal thyroidectomy or when preablation diagnostic scan uptake is #x3e;2%, higher doses are associated with improved ablation rates. Historical series demonstrate conflicting findings of long-term cancer control rates between dose levels; long-term results from modern series have yet to be reported. For high-risk patients, including those with positive surgical margins, gross extrathyroidal extension, lymph node involvement, subtotal thyroidectomy, or #x3e;5% uptake, higher-dose RAI therapy appears to provide superior rates of ablation and cancer control.

      Eur Thyroid J
  • Tremelimumab-Induced Graves Hyperthyroidism

    • Abstract: Tremelimumab and ipilimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and have been used as immunotherapies against immune checkpoints that suppress T-cell activation. Anti-CTLA-4 antibody-based therapies have been shown to be effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and thyroid disorder have been reported, mostly developed within the first year of receiving treatment. We report a case of tremelimumab-induced Graves hyperthyroidism in a 55-year-old man who was diagnosed with metastatic melanoma after 8 years of tremelimumab therapy. He had no personal or family history of thyroid or autoimmune diseases. His biochemical profile was in keeping with Graves disease, with raised serum free thyroid hormones, suppressed thyroid-stimulating hormone concentration, and raised thyrotropin receptor antibody level. He was treated with carbimazole as part of the block and replace therapy, without complications. Tremelimumab therapy was temporarily discontinued and recommenced when he was rendered biochemically euthyroid. There has been no further relapse of Graves hyperthyroidism since the discontinuation of block and replace therapy. The mechanistic profile of anti-CTLA-4-induced thyroid dysfunction and the long-term endocrine safety of this therapeutic approach remain unclear. It is important to monitor thyroid functions in patients receiving anti-CTLA-4 therapies, as their effects on endocrine systems could be more latent or prolonged than the data from current clinical trials suggest. Antithyroid drug therapy was safe and effective alongside anti-CTLA-4 therapy without compromising antitumour treatment efficacy.

      Eur Thyroid J
  • Lymph Node Metastases in Papillary and Medullary Thyroid Carcinoma Are
           Independent of Intratumoral Lymphatic Vessel Density
    • Abstract: Background: Blood and lymph vessel invasion are well-recognized markers of tumor aggressiveness, as these are the routes that lead to metastases. Thyroid tumors, depending on the histological variant, tend to have distinctive biological behaviors and use different vascular routes to metastasize, yet the mechanisms underlying the metastatic process are still poorly understood. Objectives: The aim of this study was to assess how the lymph vessel density (LVD) in different histological types of thyroid tumors, and in their surrounding tissue, correlate with the presence of lymph node metastases (LNM) and tumor pathological features. Methods: Lymph vessels of papillary thyroid carcinomas (PTC), of the classical (CVPTC, n = 50) and follicular variants (FVPTC, n = 18), and medullary thyroid carcinomas (MTC, n = 34) were immunohistochemically stained against antigen D2-40. The stained area was quantified using a computerized morphometric analysis tool and correlated with the tumor pathological characteristics. Results: LVD within all analyzed thyroid tumor subtypes was significantly lower than in the surrounding thyroid tissues (p < 0.001). Despite intratumoral LVD being significantly higher in CVPTC than in FVPTC, and peritumoral LVD being significantly higher in MTC than in PTC (p < 0.05), no correlations were found between LVD (either intratumoral or peritumoral) and the presence of lymph node metastasis. Conclusions: As no LVD differences were found amongst thyroid tumors with or without LNM, dissemination is more likely to depend on the tumor ability to invade the abundant lymph vessel network of the surrounding thyroid tissue than on the ability of the tumor to promote de novo lymphangiogenesis.
      Eur Thyroid J
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Heriot-Watt University
Edinburgh, EH14 4AS, UK
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