An assessment of the relationship between thyroid nodule characteristics, insulin resistance and arterial stiffness in euthyroid nodular goiter.

OBJECTIVES: Publications suggesting that thyroid nodule might be associated with insulin resistance and metabolic syndrome are quite interesting. There is a need for studies assessing the relationship between nodule presence and cardiovascular risk in individuals with non-functioning nodular goiter. The purpose of the present study is to reveal whether or not insulin resistance, nodule presence, and nodule stiffness affect arterial stiffness, which is a reliable and valid cardiovascular risk indicator, in individuals with euthyroid nodular goiter using the pulse wave analysis (PWA). MATERIALS AND METHODS: 50 patients with euthyroid nodular goiter and 50 healthy volunteers were included in the study. All participants were examined by B-mode thyroid ultrasound, and the participants in the nodular goiter group were also examined by strain elastography (SE). The strain index of nodules was calculated according to the Rago scoring. Also, fasting plasma glucose (FPG) and insulin levels were measured, and HOMA-IR. Arterial stiffness measurements of the participants were performed using a PWA device which employs a cuff-based oscillometric method from the brachial artery. RESULTS: PWV was found to be significantly higher in the euthyroid nodular goiter group (p < 0.001). PWV was found to be positively correlated with FPG and waist circumference. Fasting plasma glucose was found to be higher in the group with nodular goiter (p = 0.03). However, no difference was found between the groups in terms of HOMA-IR and insulin level. HOMA-IR was not correlated with thyroid volume, nodule volume, and nodule count. Also, HOMA-IR was not correlated with strain index value and PWA data. CONCLUSION: We found that PWV was significantly higher in patients with euthyroid nodular goiter. This result suggests that these patients may be at risk for cardiovascular disease.

Frequency assessment of BRAF mutation, KRas mutation, and RASSF1A methylation in nodular goitre based on fine-needle aspiration cytology specimens Ocena czestosci wystepowania mutacji genów BRAF, KRas oraz.

INTRODUCTION: Standard pre-operative diagnosis of nodular goitre is not always conclusive. The decision about nodular goitre surgery is increasingly based on molecular methods. The aim of the study was to determine BRAF T1799A mutation and KRas proto-oncogene mutation, and the analysis of RASSF1A promoter methylation level in cytological material obtained from FNAB specimens of thyroid nodules. MATERIAL AND METHODS: The study population consisted of 85 women and 12 men. The study material was genomic DNA isolated from peripheral blood and thyroid bioptates. Pyrosequencing was used for the evaluation of RASSF1 methylation level. KRas mutation was investigated with Sanger sequencing. BRAF mutation was analysed by standard methods of real-time amplification detection (real-time PCR) with the use of specific starters surrounding the mutated site. RESULTS: A significant positive correlation was demonstrated between mean methylation of four CpG islands of RASSF1A gene and thyroid tumour volume and its largest diameter (p < 0.05). KRas mutation was not detected in any of the 97 patients. In 7/85 subjects (8.2%) BRAF mutation was observed. In 6/7 patients with BRAF mutation, FNAB of thyroid nodules confirmed a benign nature of the lesions; the material was non-diagnostic in one patient, and papillary thyroid cancer was diagnosed on the basis of postoperative histopathology assessment. CONCLUSIONS: The results of genetic tests reported in our study indicate that the presence of BRAF mutation or higher RASSF1A methylation levels in FNAB cytology specimens of benign lesions may be useful in the assessment of oncological risk, while the evaluation of KRas proto-oncogene mutation is not a valuable test in pre-operative diagnosis of nodular goitre.

Assessment Of Plasma B-Catenin Concentration As Biomarker Of Thyroid Cancer.

UNLABELLED: New diagnostic methods for thyroid diseases are still being searched for. Immunohistochemical diagnosis is expanded by the introduction of new biomarkers including ß-catenin (B-Cat). Associations are indicated between the cellular expression of this biomarker and tumor stage, nodal metastases and the degree of tumor cell differentiation. Reports are scarce regarding the plasma level of this biomarker in malignant neoplastic diseases. The aim of the study was to analyze the plasma B-Cat concentration and the possibility of it use in the diagnostics of patients with nodular goiter and papillary thyroid carcinoma. MATERIAL AND METHODS: Plasma B-Cat concentration was determined in 64 patients with goiter and 15 healthy volunteers. The final histopathological examination revealed 41 cases of papillary thyroid carcinoma (PTC) and 13 cases of nodular goiter (NG). RESULTS: A significant increase in B-Cat (p <0.05) in both groups compared to the control group. No differences in the concentrations of biomarker was demonstrated between the PTC and NG groups. After determining the AUC for the tested biomarker, the B-Cat ratio of the area value 0.721 was the strong diagnostic test. CONCLUSIONS: Changes in the plasma B-Cat concentration can be the biomarker of thyroid cancer but it cannot be used for the detection of papillary thyroid carcinoma because of concomitant tumor-like lesions in the thyroid gland.

Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

DESIGN: Patients with Pendred syndrome have genotypic and phenotypic variability, leading to challenges in definitive diagnosis. Deaf children with enlarged vestibular aqueducts are often subjected to repeated investigations when tests for mutations in SLC26A4 are abnormal. This study provides genotype and phenotype information from patients with suspected Pendred syndrome referred to a single clinical endocrinology unit. METHODS: A retrospective analysis of 50 patients with suspected Pendred syndrome to investigate the correlation between genetic, perchlorate discharge test (PDT) and endocrine status. RESULTS: Eight patients with monoallelic SLC26A4 mutations had normal PDT. Of the 33 patients with biallelic mutations, ten of 12 patients with >30% discharge developed hypothyroidism. In our cohort, c.626G>T and c.3-2A>G result in milder clinical presentations with lower median perchlorate discharge of 9.3% (interquartile range 4-15%) compared with 40% (interquartile range 21-60%) for the remaining mutations. Eight novel mutations were detected. All patients with PDT <30% remained euthyroid to date, although the majority are still under the age of 30. There was a significant correlation between PDT and goitre size (R=0.61, P=0.0009) and the age of onset of hypothyroidism (R=-0.62, P=0.0297). In our population, the hazard of becoming hypothyroid increased by 7% per percentage point increase in PDT (P<0.001). CONCLUSION: There is a correlation between SLC26A4 genotype and thyroid phenotype. If results hold true for larger patient numbers and longer follow-up, then for patients with monoallelic mutations, PDT could be unnecessary. Patients with biallelic mutations and PDT discharge >30% have a high risk of developing goitre and hypothyroidism, and should have lifelong monitoring.

The use of ultrasound elastography in the assessment of malignancy risk in thyroid nodules and multinodular goitres.

OBJECTIVE: The objective of our work is to use a surgical series to analyse the validity of elastography in evaluating the malignancy of thyroid nodules and multinodular goitres. PATIENTS AND METHODS: The study examined 156 patients, 134 women (85·9%) and 22 men (14·1%), who underwent surgery for nodular thyroid disease between October 2008, and November 2010. The average age of the patients was 52 years (±14·42). Thirty-six patients (23·1%) presented with a single nodule, and 120 (76·9%) exhibited multinodular goitres. Prior to surgical intervention, all patients underwent colour eco-elastography using a qualitative five-point ordinal scale for nodule classifications. Test results were analysed using a receiver operating characteristic (ROC) curve, and an anatomical pathologic examination of surgical specimens was used as a gold standard diagnostic tool for comparison. RESULTS: Of the 192 nodules analysed, 28 (14·6%) were malignant. Using elastography data, an ROC curve was obtained with an area under the curve of 0·662 (±0·060) and a 95% confidence interval (CI 95%) between 0·545 and 0·779 (P = 0·006). By establishing a cut-off point that classified thyroid nodules with an elastographic value greater than or equal to 3 as malignant, we achieved a sensitivity of 75%, specificity of 45·73%, positive predictive value of 19·1% and negative predictive value of 91%. The positive and negative likelihood ratios were 1·38 and 0·55, respectively. CONCLUSIONS: Ultrasound elastography can provide information regarding malignancy risk in thyroid nodules and multinodular goitres. However, the sensitivity and specificity values obtained in our study are below those reported by other groups, a finding that calls into question the current clinical utility of ultrasound elastography.

German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease.

INTRODUCTION: Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines. METHODS: Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations. RESULTS: The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes. CONCLUSIONS: Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines.

Assessment of nodular goitre.

Nodular goitres are enlargements of the thyroid gland. In the absence of thyroid dysfunction, autoimmune thyroid disease, thyroiditis and thyroid malignancy, they constitute an entity described as non-toxic nodular goitre, which occurs both endemically and sporadically. In the early phase of goitrogenesis, goitres are diffuse and, with time, such goitres tend to become nodular. Concomitantly, thyroid function often becomes autonomous, and therefore the patients gradually develop hyperthyroidism. Some non-toxic goitre patients have no symptoms at all, or just complaints of cosmetic disfigurement. In the diagnostic evaluation protocol, neck palpation and several imaging methods are available: ultrasonography (US), the new developed US elastography, scintigraphy, computed tomography (CT) scan and magnetic resonance imaging (MRI). Fine-needle aspiration biopsy (FNAB) provides the most direct and specific information about a thyroid nodule. Recently, a combination of cytology and molecular testing has shown significant improvement in the diagnostic accuracy and allowed for better prediction of malignancy in thyroid nodular disease.

Assessment of cyclin D1 gene expression as a prognostic factor in benign and malignant thyroid lesions.

OBJECTIVE: Cyclin D1, encoded by CCND1 (cyclin D1) gene with locus in chromosome 11q13, is a protein that plays the key role in the passage through the restriction point in G1 phase of cell cycle. The aim of the study were: 1) an assessment of CCND1 gene expression level in benign and malignant thyroid lesions and 2) the evaluation of possible correlations between gene expression and the histopathological variants of papillary thyroid carcinoma (PTC), or tumour size, classified according to TNM definition of primary tumours (in case of PTC only) or patient's sex or age. DESIGN: Thirty five (35) tissue samples were analysed: 24 cases of PTC, 4 cases of medullary thyroid carcinoma (MTC), 4 cases of follicular adenoma (FA) and 3 cases of nodular goitre (NG). In real-time polymerase chain reaction (real-time PCR), two-step RT-PCR (reverse transcriptase-polymerase chain reaction) in an ABI PRISM 7500 Sequence Detection System was employed. Cyclin D1 gene expression level was assessed, calculating the mean relative quantification rate (RQ rate) increase for each sample. RESULTS: The level of cyclin D1 gene expression was significantly higher in malignant thyroid tumours (PTC, MTC), as compared with that in macroscopically unchanged thyroid tissue, FA and/or NG groups. However, the differences of RQ rate value between different PTC variants were statistically insignificant. No correlation was found between RQ values and patients' sex or age. On the other hand, the correlation was observed between RQ values and tumour size. CONCLUSIONS: Cyclin D1 gene expression in various thyroid lesions may be helpful in diagnostically doubtful cases. However, our results--mostly due to the small numbers of cases in the groups other than PTC--do not yet allow considering cyclin D1 gene as a molecular prognostic marker.

Hyperthyroidism and complete atrioventricular block--a report of 2 cases with electrophysiologic assessment.

Although cardiovascular manifestations in thyroid disorders are frequently encountered in clinical practice, atrioventricular (AV) conduction disorders, especially in hyperthyroidism, are rare. There are some proposed mechanisms for AV blocks in hyperthyroidism but the exact mechanism is still unknown. The authors report 2 cases with thyroid function disorders and complete AV block, and the electrophysiologic characteristics of these 2 patients, and they review and speculate on similar reported cases.

Thyroidectomy or radioiodine? The value of ultrasonography and cytology in the assessment of nodular lesions in Graves' hyperthyroidism.

Although diffuse toxic goiter is a classical feature of Graves' disease (GD) nodular goiters are occasionally found in some patients. The aim of the present study was to investigate the ultrasonographic and corresponding cytological manifestations in GD patients with nodular lesions to decide on a therapeutic strategy. Twenty-seven consecutive GD patients with nodular goiter were included in this study (21 women and six men, mean age 41.2 years, range 22-77 years). All underwent thyroid ultrasonography and fine-needle aspiration cytology. Of the 27 patients eight underwent surgical intervention because papillary thyroid carcinoma or follicular neoplasm was diagnosed by cytology; five of these were shown to have papillary thyroid carcinomas. Ultrasonography revealed the malignant nodules to be hypoechogenic, heterogeneous, and with ill-defined margins in four of these five thyroid cancers, whereas the remaining sonogram showed a cystic change and cauliflower-like tumor formation with microcalcification. The volume and maximal diameter of cancerous nodules were significantly larger than those of benign nodules. In conclusion our results reveal that ultrasonography and fine-needle aspiration cytology are reliable and quick methods for diagnosing nodular goiters in GD patients. If thyroid neoplasms are found ablative therapy with thyroidectomy is indicated instead of radioactive iodine.

Clinical and economic impact of incidental thyroid lesions found with CT and MR.

PURPOSE: To estimate the prevalence and the clinical and economic consequences of management strategies for thyroid lesions detected incidentally on cross-sectional imaging of the head and neck. METHODS: Two hundred consecutive CT scans and 200 consecutive MR images of the neck performed over a 1-year period in patients being examined for other purposes were reviewed retrospectively to determine the prevalence of unexpected thyroid lesions. After excluding patients with prior thyroidectomies, known thyroid disease, and inadequate examinations, 231 imaging studies were analyzed. RESULTS: Incidental thyroid lesions were originally reported in 14 (6%) of the 231 patients, but an additional 22 (9.5%) were found on retrospective review for a total of nearly 16% (36 of 231). Six of the 36 patients received further workup, consisting of nuclear medicine scintigraphy (n = 3), sonography (n = 3), thyroid function tests (n = 5), fine-needle aspiration (n = 4), and thyroid lobectomy (n = 1). Final diagnoses, obtained in four of the six patients, included three multinodular goiters and one follicular adenoma. Two patients, one with nondiagnostic findings at fine-needle aspiration and a second with normal thyroid function test results, are being followed up. The mean cost of the workup and treatment per examined patient was $1158. CONCLUSION: Incidental thyroid lesions are frequently present and often overlooked on cross-sectional images of the neck in patients being examined for other reasons. The cost of pursuing a workup of these lesions and their high prevalence in the population raise questions regarding appropriate management strategies.

Follicular neoplasms of the thyroid. Decision tree approach using morphologic and morphometric parameters.

OBJECTIVE: Fine needle aspiration of the thyroid is limited in differentiating hyperplastic nodular goiters from true follicular neoplasms and in separating follicular adenomas from follicular carcinomas. The present study was done to evaluate if a panel of morphologic and morphometric parameters of the thyroid and ploidy status, either alone or in combination, would help differentiate hyperplastic nodular goiters from follicular adenomas and carcinomas. STUDY DESIGN: Fine needle aspiration smears of 75 cases classified as follicular neoplasms of the thyroid were studied for morphologic (cellularity, colloid and cellular patterns) and morphometric parameters (nuclear diameters and nucleoli). RESULTS: Of the large number of parameters utilized in this study, only two of the cellular patterns (honeycomb and single dispersed) and the average maximum nuclear diameter showed trends in differentiating these lesions. CONCLUSION: Based on these patterns and nuclear diameter (9 microns), we developed a decision tree classification that separated the benign from malignant lesions (follicular carcinomas) with a sensitivity and specificity of 92.8% and 57.4%, respectively.

Thyroid function tests. Selective use for cost containment.

Clinicians often obtain a variety of thyroid function tests in patients suspected of having thyroid disease when only a few are necessary to adequately establish a diagnosis and do follow-up. For hyperthyroidism and hypothyroidism, measurement of serum T4 is the best screening test. The serum T3 resin uptake test should be added with women suspected of being hyperthyroid because of the changes produced by pregnancy or estrogen-containing contraceptives. Various imaging techniques, including RAI, ultrasound, CT, and MRI, are often used for differentiating benign or cystic thyroid nodules from malignant or solid ones. Each of the available techniques has a different cost, and each is most suitable for a particular disorder. Special tests (eg, TRH testing and measurement of serum TBG) should be added to the basic screening tests only for questionable cases to differentiate diagnostic possibilities or confirm an uncertain diagnosis.