Identification of a Novel Non-V600E BRAF Mutation in Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) is a common endocrine malignancy, and its incidence is reported to be constantly increasing. BRAF mutation is detected in approximately 44% of PTCs, and the most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). Although BRAFV600E represents 95% of all BRAF mutations, uncommon BRAF mutations have been reported in thyroid carcinomas and represent an alternative mechanism of BRAF activation with unclear clinical significance.

High Incidence of Thyroid Cancer in Southern Tuscany (Grosseto Province, Italy): Potential Role of Environmental Heavy Metal Pollution.

The incidence of thyroid cancer (TC) in Italy is one of the highest in Europe, and the reason for this is unclear. The intra-country heterogeneity of TC incidence suggests the possibility of an overdiagnosis phenomenon, although environmental factors cannot be excluded. The aim of our study is to evaluate the TC incidence trend in southern Tuscany, Italy, an area with particular geological characteristics, where the pollution and subsequent deterioration of various environmental matrices with potentially toxic elements (heavy metals) introduced from either geological or anthropogenic (human activities) sources are documented.

Risk of Second Malignant Neoplasm in Familial Non-Medullary Thyroid Cancer Patients.

Introduction: Survival rates in patients with non-medullary thyroid carcinoma (NMTC) are high, increasing the possibility to develop a second malignant neoplasm (SMN). Many studies investigated the relationship between increased risk of SMN in NMTC patients treated with radioiodine, but few data are available about the impact of family history (FH) of thyroid cancer on SMN risk.

Purpose: To assess the risk of SMN in a large cohort of sporadic and familial NMTC using the standardized incidence ratio (SIR).

Calcitonin Levels in Thyroid Disease Are Not Affected by Autoimmune Thyroiditis or Differentiated Thyroid Carcinoma.

Introduction: Association between hypercalcitoninemia and pathological conditions such as autoimmune thyroiditis (AIT) or differentiated thyroid carcinoma (DTC) has been addressed, with conflicting results. We evaluated the prevalence and the clinical relevance of elevated basal serum calcitonin (CT) levels in non-neoplastic (nodular goiter [NG] and AIT) and neoplastic thyroid diseases (DTC).

Methods: We retrospectively evaluated 3,250 consecutive patients with thyroid nodular disease who underwent fine-needle aspiration cytology with adequate sample.

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel missense mutation in AVP gene in a large Italian kindred.

Purpose: Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body's level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants.

Methods: In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene.

The Combination of Sonographic Features and the Seven-Gene Panel May be Useful in the Management of Thyroid Nodules With Indeterminate Cytology.

Introduction: The management of patients with indeterminate thyroid nodules, which account for 10-25% of thyroid fine needle aspiration biopsies (FNABs), is still very challenging.

Aim: To verify the utility of the seven-gene panel in combination with ultrasound features in the clinical management of indeterminate thyroid nodules.

Results: The study group included 188 indeterminate thyroid nodules, divided into TIR3A (56.

Improvement of Overall Survival Using TKIs as Salvage Therapy in Advanced Thyroid Carcinoma: Real-Life Data on a Single Center Experience.

Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer.

Preliminary results from whole-genome expression analysis in patients with secondary adrenal insufficiency treated with modified-release hydrocortisone.

Purpose: Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters.

Long-Term Clinical Outcome in Familial and Sporadic Papillary Thyroid Carcinoma.

Background: The definition and the behaviour of familial papillary thyroid cancer (FPTC) compared to the sporadic form (SPTC) are still debated. Some authors believe that only families with 3 or more affected members represent an actual example of familial diseases.

Objectives: The objective of the study was to analyse the clinicopathological features and the outcome of sporadic and familial PTC patients also according to the number of affected members.

Validation of American Thyroid Association Ultrasound Risk-Adapted Approach for Repeating Cytology in Benign Thyroid Nodules.

The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be performed. In addition, this system is used to plan the long-term follow-up of patients with cytological benign thyroid nodules. The aim of our study was to evaluate the ATA US risk-adapted approach for repeating cytology in a large retrospective cohort of consecutive benign nodules with a second FNAC repeated after a median follow-up of 3.

Prospective Validation of ATA and ETA Sonographic Pattern Risk of Thyroid Nodules Selected for FNAC.

Context: Recently, the American Thyroid Association (ATA) and the European Thyroid Association (ETA) have proposed that thyroid ultrasound (US) should be used to stratify the risk of malignancy in thyroid nodules and to aid decision-making about whether fine-needle aspiration cytology (FNAC) is indicated.

Objective: To validate and to compare the ATA and ETA US risk stratification systems of thyroid nodules in a prospective series of thyroid nodules submitted to FNAC.

Setting: We prospectively evaluated 432 thyroid nodules selected for FNAC from 340 patients.

Telomere abnormalities and chromosome fragility in patients affected by familial papillary thyroid cancer.

Introduction: Genomic instability has been proposed to play a role in cancer development and can occur through different mechanisms including telomere association and telomere loss. Studies carried out in our unit have demonstrated that familial papillary thyroid cancer (fPTC) patients display an imbalance, at the germinal level, in telomere-telomerase complex.

Aim: We aimed to verify whether familial fPTC patients show an increased spontaneous chromosome fragility.

Lack of mutations of the telomerase RNA component in familial papillary thyroid cancer with short telomeres.

Background: The occurrence of familial papillary thyroid cancer (FPTC) is well established but no susceptibility genes for this disease have been discovered. Our group has recently demonstrated that patients with FPTC have shorter telomeres, not associated with mutations in telomerase reverse transcriptase, gene than patients with sporadic papillary thyroid cancer (SPTC), healthy subjects (HS), and unaffected family members (UFMs). Several diseases, however, have short telomeres associated with mutations in the telomerase RNA component (TERC) gene or in the shelterin complex (POT1, RAP1, TIN2, TPP1, TRF1, and TRF2) genes.

Telomere length in neoplastic and nonneoplastic tissues of patients with familial and sporadic papillary thyroid cancer.

Introduction: Many studies have found an association between altered telomere length (TL), both attrition or elongation, and cancer phenotype. Recently, we have reported that patients with the familial form of papillary thyroid cancer (FPTC) have short telomeres in blood leucocytes.

Aim: To evaluate relative TL (RTL) at somatic level in neoplastic and nonneoplastic tissues of patients with FPTC (n = 30) and sporadic PTC (n = 46).

Telomerase and the endocrine system.

Telomeres are nucleoprotein complexes located at the ends of chromosomes that have a critical role in the maintenance of chromosomal integrity. This involvement is based on complex secondary and tertiary structures that rely on DNA-DNA, DNA-protein and protein-protein interactions. De novo synthesis and maintenance of telomere repeats is controlled by telomerase, a specialized complex that consists of a telomerase RNA component and a protein component--telomerase reverse transcriptase.

Lack of germline A339V mutation in thyroid transcription factor-1 (TITF-1/NKX2.1) gene in familial papillary thyroid cancer.

Thyroid cancer may have a familial predisposition but a specific germline alteration responsible for the disease has not been discovered yet. We have shown that familial papillary thyroid cancer (FPTC) patients have an imbalance in telomere-telomerase complex with short telomeres and increased telomerase activity. A germline mutation (A339V) in thyroid transcription factor-1 has been described in patients with multinodular goiter and papillary thyroid cancer.

Telomeres and thyroid cancer.

Telomeres are specialized structures at the ends of chromosomes, consisting of hundreds of repeated hexanucleotides (TTAGGG)n. Genetic integrity is partly maintained by the architecture of telomeres and it is gradually lost as telomeres progressively shorten with each cell replication, due to incomplete lagging DNA strand synthesis and oxidative damage. Telomerase is a reverse transcriptase enzyme that counteracts telomere shortening by adding telomeric repeats to the G-rich strand.

Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology.

Context: Fine-needle aspiration cytology (FNAC) is the gold standard for the differential diagnosis of thyroid nodules but has the limitation of inadequate sampling or indeterminate lesions.

Objective: We aimed to verify whether search of thyroid cancer-associated protooncogene mutations in cytological samples may improve the diagnostic accuracy of FNAC.

Study Design: One hundred seventy-four consecutive patients undergoing thyroid surgery were submitted to FNAC (on 235 thyroid nodules) that was used for cytology and molecular analysis of BRAF, RAS, RET, TRK, and PPRgamma mutations.

Short telomeres, telomerase reverse transcriptase gene amplification, and increased telomerase activity in the blood of familial papillary thyroid cancer patients.

Background: Differentiated papillary thyroid cancer is mostly sporadic, but the recurrence of the familial form has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer.

Objective: The aim of our work was to study the telomere-telomerase complex in the peripheral blood of patients with familial papillary thyroid cancer (FPTC), including the measurement of relative telomere length (RTL), telomerase reverse transcriptase (hTERT) gene amplification, hTERT mRNA expression, telomerase protein activity, and search of hTERT or telomerase RNA component gene mutations.

Clinical features and therapeutic implication of papillary thyroid microcarcinoma.

Papillary thyroid microcarcinomas (PTMs) are small tumors (< or =1 cm of diameter) that belong to the well-differentiated low-risk carcinomas of the thyroid, which are characterized by benign behavior, probably of little clinical significance, and do not affect patients' survival. They are found in otherwise normal thyroids or in multinodular goiters with a clinical frequency varying substantially according to different series. Sometimes, PTM may be associated with lymph node metastases at presentation and/or locoregional recurrences during follow-up.

Ectopic intrathyroidal nonfunctioning parathyroid cyst.

Objective: To describe a rare case of ectopic intrathyroidal parathyroid cyst (PC) in a 29-year-old woman who had been referred to us because of a multinodular goiter.

Methods: We review the clinical, laboratory, and radiographic findings as well as the treatment in our patient and provide a brief discussion of the associated literature.

Results: Ultrasonography of the neck showed the presence of 2 thyroid nodules in the left lobe, the larger of which was solid and the smaller of which had a cystic appearance.

Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells.

We previously demonstrated that the human nicotinamide N-methytransferase (NNMT) gene was highly expressed in many papillary thyroid cancers and cell lines. The expression in other papillary and follicular cancers or cell lines and normal thyroid cells was low or undetectable. To gain an understanding of the molecular mechanism of this cell-specific expression, the NNMT promoter was cloned and studied by luciferase reporter gene assay.

Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.

Background: The development of antibodies to thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone (TSH) receptor is a main feature of autoimmune thyroid diseases.

Objective: To investigate whether complete removal of thyroid antigens results in the abatement of humoral thyroid autoimmunity.

Design: Retrospective chart review study of patients treated and monitored with a standard prospective protocol.