Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Posthemithyroidectomy Hypothyroidism: Updated Meta-Analysis of Risk Factors and Rates of Remission.

INTRODUCTION: The aim of this study was to determine the incidence and risk factors for hypothyroidism, both clinical and subclinical, following hemithyroidectomy in preoperatively euthyroid patients, as well as hypothyroidism remission and its time of remission. MATERIALS AND METHODS: A search was performed in Medline (via PubMed), Web of Science, and the Cochrane Library using the keywords "hemithyroidectomy + postoperative + hypothyroidism" and "hemithyroidectomy + hormone supplementation". RESULTS: Fifty-four studies with a total of 9,999 patients were included. After a mean follow-up interval of 48.2 mo, the pooled hypothyroidism rate was 29%. The subclinical hypothyroidism rate was 79% of patients with hypothyroidism (18 studies). Moreover, a meta-analysis of 12 studies indicated a pooled hypothyroidism remission rate after hemithyroidectomy of 42% (95% CI: 24%-60%). Older patient age (MD = -2.54, 95% CI = -3.99, -1.10, P = 0.0006), female gender (OR = 0.69, 95% CI = 0.58, 0.82, P < 0.0001), higher preoperative thyroid-stimulating hormone levels (MD = -0,81, 95% CI = -0.96, -0.66, P < 0.00001), pathological preoperative anti-thyroid peroxidase antibodies (OR = 0.37, 95% CI = 0.24, 0.57, P < 0.00001) and anti-thyroglobulin antibodies (OR = 0.52, 95% CI = 0.36, 0.75, P = 00,005), and right-sided hemithyroidectomy (OR = 0.54, 95% CI = 0.43, 0.68, P < 0.00001) were associated with postoperative hypothyroidism development. In metaregression analysis, Asia presented a significantly higher hypothyroidism rate after hemithyroidectomy (34.6%, 95% CI = 29.3%-9.9%), compared to Europe (22.9%, 95% CI = 16.2%-29.5%, P = 0.037) and Canada (1.8%, 95% CI = -22.6%-26.2%, P = 0.013). CONCLUSIONS: Hypothyroidism is a frequent and significant postoperative sequela of hemithyroidectomy, necessitating individualization of treatment strategy based on the underlying disease as well as the estimated risk of hypothyroidism and its risk factors.

BRAFV600E, BANCR, miR-203a-3p and miR-204-3p in Risk Stratification of PTC Patients.

In order to enhance the risk stratification of papillary thyroid carcinoma (PTC) patients, we assessed the presence of the most common mutation in PTC (BRAFV600E) with the expression profiles of long non-coding RNA activated by BRAFV600E (BANCR) and microRNAs, which share complementarity with BANCR (miR-203a-3p and miR-204-3p), and thereafter correlated it with several clinicopathological features of PTC. BRAFV600E was detected by mutant allele-specific PCR amplification. BANCR and miRs levels were determined by quantitative RT-PCR. Bioinformatic analysis was applied to determine the miRs' targets. The expression profile of miR-203a-3p/204-3p in PTC was not affected by BRAFV600E. In the BRAFV600E-positive PTC, high expression of miR-203a-3p correlated with extrathyroidal invasion (Ei), but the patients with both high miR-203a-3p and upregulated BANCR were not at risk of Ei. In the BRAFV600E-negative PTC, low expression of miR-204-3p correlated with Ei, intraglandular dissemination and pT status (p < 0.05), and the mutual presence of low miR-204-3p and upregulated BANCR increased the occurrence of Ei. Bioinformatic analysis predicted complementary binding between miR-203a-3p/204-3p and BANCR. The co-occurrence of tested factors might influence the spreading of PTC. These findings partially describe the complicated network of interactions that may occur during the development of PTC aggressiveness, potentially providing a new approach for high-risk PTC patient selection.

The clinical and histopathological characteristics of thyroid gland diseases in adolescents requiring surgical treatment: a ten-year follow-up study.

The present research aimed to determine the clinical and pathohistological characteristics of thyroid gland diseases in adolescents who were previously surgically treated at the Endocrine Surgery Center of the University Medical Center of Serbia from 01/01/2001 to 01/01/2011. The study covered 170 patients of both sexes from the population of adolescents (aged 16 to 20 years) with various malignant and benign thyroid gland diseases. The data for this study were extracted from the medical histories of patients and the electronic database of the Center for Endocrine Surgery. Detailed data analysis included diagnosis, symptomatology, surgical intervention type, and disease stage. The following thyroid status parameters were analyzed from preoperative data: thyroxine (T4), thyroxine free fraction (FT4), triiodothyronine (T3), triiodothyronine free fraction (FT3), and thyroid stimulating hormone (TSH). In addition, the pathohistological features of diagnosed thyroid diseases were also determined, with a special focus on the presence of well-differentiated cancers. Papillary carcinomas were the most common of well-differentiated cancers in adolescents over the ten-year follow-up period. Based on the assessed data, total thyroidectomy was the most commonly used type of surgical intervention in these patients. The conducted research provides essential information related to both the biological characteristics and diagnostics of these cancers and their surgical treatment in such a sensitive population. Moreover, research showed that the clinical presentation of thyroid cancer in adolescents is almost identical to that in adults.

Expression of pY397-FAK and Its miR Regulators Drive Dedifferentiation in the Thyroid Neoplasia Spectrum.

Thyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 and on a posttranslational level by autophosphorylation at Y397 (pY397-FAK). We related regulators of FAK with histologic dedifferentiation, clinicopathological factors, and differential diagnosis in the thyroid neoplasia spectrum. We classified 82 cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variants of papillary thyroid carcinoma (PTC), dedifferentiated PTC, and anaplastic carcinoma. MiRs were analyzed by RT-qPCR. Protein expression of pY397-FAK was analyzed by immunohistochemistry (separately in the membrane, cytoplasm, and nuclear compartment) and Western blot. All three miRs were upregulated in healthy tissue compared to malignant, while pY397-FAK was downregulated. MiRs and pY397-FAK were not mutually correlated. MiR-135a-5p was decreasing while membranous and cytoplasmic pY397-FAK increased with dedifferentiation. Neither miR correlated with clinicopathological factors. MiR-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK discriminated the follicular from the classical variant of PTC. Disturbances of FAK regulation on different levels contribute to neoplastic dedifferentiation. pY397-FAK exerts its oncogenic role in the membrane and cytoplasm. Diagnostically, miRs-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK differentiated between classical and follicular PTC.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Parathyroid carcinoma in chronic renal disease - a case series of three patients and review of literature.

BACKGROUND: Apart from being a rare endocrine tumor, parathyroid carcinoma is also one of the rarest malignancies in human beings. Parathyroid carcinoma is even more uncommon in haemodialysis patients with end-stage renal disease. The pathogenesis of parathyroid hyperplasia in haemodialysis patients is well known, but the mechanism of development of parathyroid carcinoma in these patients remains unclear. METHODS: Three cases of parathyroid carcinoma in haemodialysis patients are presented in this study: a 69-year-old male patient and two female patients (67 and 61 years old). In all cases parathyroid carcinoma infiltrated the ipsilateral thyroid lobe and in one patient the right laryngeal nerve was involved as well. One patient underwent three surgical procedures. RESULTS: After surgical treatment, all patients were normocalcaemic and showed a significant reduction in PTH levels. CONCLUSION: In patients with secondary hyperparathyroidism, who develop parathyroid carcinoma, surgical resection is the only viable treatment option.

MiR-203a-3p, miR-204-3p, miR-222-3p as useful diagnostic and prognostic tool for thyroid neoplasia spectrum.

PURPOSE: The challenge in the diagnosis and treatment of thyroid carcinoma is to correctly classify neoplasias with overlapping features and to identify the high-risk patients among those with a less aggressive form, in order to personalize the treatment of thyroid carcinoma patients accordingly. METHODS: MiR-203a-3p, miR-204-3p, and miR-222-3p levels were determined in 99 cases of thyroid neoplasias (77 papillary thyroid carcinomas (PTC) of diverse variants, 12 follicular thyroid adenomas (FTA) and 10 nodular goiters (NG)) along with 99 adjacent non-malignant thyroid tissues using quantitative RT-PCR. The results were evaluated in comparison with the clinicopathological features of the patients and available TCGA data. RESULTS: Down-regulated miR-203a-3p indicates the presence of thyroid tumor (PTC or FTA) with high sensitivity (75%) and specificity (73%), while its up-regulation indicates NG. If miR-203a-3p is down-regulated, up-regulated miR-204-3p with high sensitivity (83.3%) and specificity (74.4%) indicates FTA presence, while up-regulated miR-222-3p, with high sensitivity (76.6%) and specificity (75.0%), points to PTC. The expression of miR-204-3p and miR-222-3p depends on the PTC subtype (P < 0.05). While the deregulated expression of tested miRs is associated with a long-range of unfavorable clinicopathological parameters of PTC, only abundant expression of miR-222-3p may be used as an independent predictive factor for the presence of extrathyroid invasion and advanced pTNM stage of PTC (P < 0.05). CONCLUSION: Successive evaluation of miR-203a-3p, miR-204-3p, and miR-222-3p expression can help in the differential diagnosis of thyroid neoplasias. A high relative value of miR-222-3p expression is an independent predictive factor for the presence of extrathyroid invasion and advanced pTNM stage of PTC. The panel consisting of miR-203a-3p, miR-204-3p, and miR-222-3p could be used as a diagnostic and prognostic tool for personalizing the treatment of thyroid cancer patients.

Patients' Fears and Perceptions Associated with Anesthesia.

Background and Objectives: It has been suggested that intense feelings of fear/anxiety and significant patient concerns may affect the perioperative course. Those findings emphasize the importance of surgical patients' preoperative feelings. Still, current knowledge in this area is based on a limited number of studies. Thus, we think that there is a need to further explore patients' preoperative fears, better characterize risk factors and reasons for their occurrence, and evaluate patients' perspectives associated with anesthesia. Materials and Methods: A total of 385 patients undergoing vascular surgery were preoperatively interviewed using a questionnaire that included demographics and questions related to patients' fears and perceptions of anesthesia. Statistical analyses included descriptive statistics, Pearson's χ2 and McNemar tests, and multivariate ordinal logistic regression. Results: The main causes of patients' preoperative fear were surgery (53.2%), potential complications (46.5%), and anesthesia (40%). Female sex was a predictor of surgery and anesthesia-related fear (OR = 3.07, p = 0.001; OR = 2.4, p = 0.001, respectively). Previous experience lowered the fear of current surgery (OR = 0.65, p = 0.031) and anesthesia (OR = 0.6, p = 0.017). Type of surgery, type of anesthesia, educational and socioeconomic status, and personal knowledge of an anesthesiologist affected specific anesthesia-related fears. Over 25% of patients did not know that an anesthesiologist is a physician, and only 17.7% knew where anesthesiologists work. Level of education and place of residence influenced patients' perceptions of anesthesia. Conclusions: Anesthesia-related fears are affected by the type of surgery/anesthesia, experience with previous surgery, and personal knowledge of an anesthesiologist. Women, patients with lower education levels, and patients with poorer socioeconomic status are at higher risk of developing those fears. The perception of anesthesiologists is inadequate, and knowledge of anesthesia is poor. Promotion of patient education regarding anesthesia is needed to alleviate those fears and increase understanding of anesthesia.

Risk Factors for New Onset Atrial Fibrillation during Thyroid Gland Surgery.

OBJECTIVE: Thyroid dysfunction is a common cause of atrial fibrillation (AF). Incidence of AF is high in patients with both expressed and subclinical hyperthyroidism. The aim of our study was to determine the incidence and predictors of new onset atrial fibrillation (NOAF) in euthyroid patients undergoing thyroid surgery. SUBJECT AND METHODS: The study included 1,252 euthyroid patients with American Society of Anesthesiologists (ASA) physical status ASA 2 and ASA 3, who were 18 years and older and were in sinus rhythm. Patients without comorbidity and patients with persistent AF were excluded. We investigated the influence of the following preoperative characteristics on the occurrence of NOAF: age, sex, body mass index, ASA score, admission diagnoses, and comorbidity. We noted the influence of difficult intubation of trachea, type and duration of surgery, and time under general anaesthesia. Univariate and multivariate logistic regression were used to determine predictors of occurrence of NOAF. RESULTS: NOAF was noted in 0.72% of patients. Patients with NOAF were older (63.11 vs. 56.81 years) than patients without NOAF, but this was not statistically significant. Significantly more patients from the NOAF group had preoperative heart rhythm disturbance and a history of angina pectoris, in contrast to patients without registered NOAF (p = 0.001; p = 0.017). Multivariate analysis showed that a history of heart rhythm disturbance was an independent predictor of NOAF. CONCLUSIONS: Incidence of NOAF during thyroid surgery is similar to the other type of surgery, if the values of thyroid hormones are normal.

Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter.

Introduction: Papillary thyroid carcinoma (PTC) and colloid goiter (CG) represent the most common thyroid malignant and benign diseases, respectively. Oxidative stress is considered to have an important role in the pathogenesis of both diseases, but without sufficient and comprehensive data. The aim was to evaluate the redox profile, its influence on cell survival of PTC, comparing it with CG as a control and its relation with demographic, pathological and clinical parameters. Material and methods: We evaluated for the first time the PTC and CG tissue profile of advanced oxidation protein products (AOPP) and total thiols as parameters of redox metabolism and deoxyribonuclease I (DNase I) and deoxyribonuclease II (DNase II) activity as biomarkers of cell turnover and apoptosis. Tissue levels of biochemical parameters were quantified in PTC and CG tissue using spectrophotometric methods. Study parameters were evaluated in light of different demographic, clinical and pathological features of PTC and CG. Results: Papillary thyroid carcinoma tissue is characterized by increased antioxidant activity and a normal prooxidation level. Biochemical parameters show numerous correlations with demographic and clinical characteristics of PTC and CG patients. DNase I and II activities are dependent upon the AOPP concentration in PTC tissue. The size of CG can be predicted with combined use of AOPP, DNase I and DNase II. AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype. Conclusions: Evaluated parameters can be used for assessment of tumor redox and survival status and the clinical course of PTC and CG.

Predictive Significance of Two MMP-9 Promoter Polymorphisms and Acetylated c-Jun Transcription Factor for Papillary Thyroid Carcinoma Advancement.

Papillary thyroid carcinoma represents a challenge from a prognostic standpoint. Molecular alterations responsible for PTC advancement include MMP-9 genetic promoter polymorphisms that bind transcription factors with varying degrees of affinity and, hence, constitute a predisposition for MMP-9 expression. We examined how two promoter polymorphisms (the -1562 C/T transition and -131 (CA)n tandem repeats) as well as levels of the c-Jun transcription factor and its modified form acetylated at Lys271 influence MMP-9 expression and PTC progression. A significant proportion of PTC samples were heterozygous for the (CA)n tandem repeat number, had a transcription-promoting T allele at -1562, and expressed high levels of c-Jun, acetylated c-Jun, and MMP-9 protein. The T allele at the -1562 position accompanied the elevated MMP-9 protein expression, while high acetylated c-Jun levels accompanied the high MMP-9 protein levels on mRNA. The -1562 C/T transition, MMP-9, and acetylated c-Jun were associated with the presence of extra-thyroid invasion and degree of tumor infiltration, while the T allele and acetylated c-Jun also correlated with tumor stage. We conclude that the -1562 MMP-9 polymorphism and levels of acetylated c-Jun affect PTC progression via modulation of MMP-9 levels. Genotyping the MMP-9 at -1562 and estimating the levels of MMP-9 and acetylated c-Jun in PTC may prove beneficial in identifying high-risk patients.

Case Control Study of Risk Factors for Occurrence of Postoperative Hematoma After Thyroid Surgery: Ten Year Analysis of 6938 Operations in a Tertiary Center in Serbia.

BACKGROUND: Post-thyroidectomy bleeding is rare, but potentially life-threatening complication. Early recognition with immediate intervention is crucial for the management of this complication. Therefore, it is very important to identify possible risk factors of postoperative hemorrhage as well as timing of postoperative hematoma occurrence. METHODS: Retrospective review of 6938 patients undergoing thyroidectomy in a tertiary center in a ten year period (2009-2019) revealed 72 patients with postoperative hemorrhage requiring reoperation. Each patient who developed postoperative hematoma was matched with four control patients that did not develop postoperative hematoma after thyroidectomy. The patients and controls were matched by the date of operation and surgeon performing thyroidectomy. RESULTS: The incidence of postoperative bleeding was 1.04%. On univariate analysis older age, male sex, higher BMI, higher ASA score, preoperative use of anticoagulant therapy, thyroidectomy for retrosternal goiter, larger thyroid specimens, larger dominant nodules, longer operative time, higher postoperative blood pressure and the use of postoperative subcutaneous heparin were identified as risk factors for postoperative bleeding. Sixty-nine patients (95.8%) bled within first 24 h after surgery. CONCLUSION: The rate of postoperative bleeding in our study is consistent with recent literature. Male sex, the use of preoperative anticoagulant therapy, thyroidectomy for retrosternal goiter and the use of postoperative subcutaneous heparin remained statistically significant on multivariate analysis (p < 0.001). When identified, these risk factors may be an obstacle to the outpatient thyroidectomy in our settings.

Preoperative Anxiety is Associated With Postoperative Complications in Vascular Surgery: A Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased morbidity and/or mortality in surgical patients. This study investigated the incidence, predictors, and association of preoperative anxiety with postoperative complications in vascular surgery. METHODS: Consecutive patients undergoing aortic, carotid, and peripheral artery surgery, under general and regional anesthesia, from February until October 2019 were included in a cross-sectional study. Anesthesiologists assessed preoperative anxiety using a validated Serbian version of the Amsterdam Preoperative Anxiety and Information Scale. Patients were divided into groups with low/high anxiety, both anesthesia- and surgery-related. Statistical analysis included multivariate linear logistic regression and point-biserial correlation. RESULTS: Of 402 patients interviewed, 16 were excluded and one patient refused to participate (response rate 99.7%). Out of 385 patients included (age range 39-86 years), 62.3% had previous surgery. High-level anesthesia- and surgery-related anxieties were present in 31.2 and 43.4% of patients, respectively. Independent predictors of high-level anesthesia-related anxiety were having no children (OR = 0.443, 95% CI: 0.239-0.821, p = 0.01), personal bad experiences with anesthesia (OR = 2.294, 95% CI: 1.043-5.045, p = 0.039), and time since diagnosis for ≥ 4 months (OR = 1.634, 95% CI: 1.023-5.983, p = 0.04). The female sex independently predicted high-level surgery-related preoperative anxiety (OR = 2.387, 95% CI: 1.432-3.979, p = 0.001). High-level anesthesia-related anxiety correlated with postoperative mental disorders (rpb = 0.193, p = 0.001) and pulmonary complications (rpb = 0.104, p = 0.042). Postoperative nausea (rpb = 0.111, p = 0.03) and postoperative mental disorders (rpb = 0.160, p = 0.002) correlated with high-level surgery-related preoperative anxiety. CONCLUSIONS: Since preoperative anxiety affects the postoperative course and almost every third patient experiences anxiety preoperatively, routine screening might be recommended in vascular surgery.

Translation and validation of the Amsterdam preoperative anxiety and information scale (APAIS) in Serbia.

OBJECTIVES: Preoperative anxiety is common and might affect surgical treatment outcomes. The aim was to translate and validate the Serbian version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS). METHODS: Following translation and initial evaluation, the Serbian version (S-APAIS) was administered to 385 patients. Internal consistency, construct validity, prognostic criteria validity, and concurrent validity between S-APAIS and Visual Analogue Scale for Anxiety (VAS-A) were evaluated. RESULTS: Factor analysis revealed two factors: APAIS-anesthesia (items 1, 2, 3) and APAIS-procedure (items 4, 5, 6). The whole scale, APAIS-anesthesia, and APAIS-procedure subscales showed an adequate level of internal consistency (Cronbach's αs: 0.787, 0.806, and 0.805, respectively). High concurrent validity was observed between APAIS-anesthesia and VAS-A (ρ = 0.628, p < .001). A moderate correlation was found between APAIS-procedure and VAS-A scale (ρ = 0.537, p < .001). At the cut-off point of 9, the area under the curve (AUC) of APAIS-anesthesia was 0.815 (95% CI: 0.77-0.85, p < .001). For the APAIS-procedure, AUC was 0.772 (95% CI: 0.73-0.81, p < .001) at the cut-off point of 8. CONCLUSION: The structure of S-APAIS substantially differs from the original and allows separate measurement of anesthesia- and procedure-related anxieties. S-APAIS is a comprehensive, valid, and reliable instrument for the measurement of preoperative anxiety.

Predictive Value of Calcium Test for Preoperative Diagnosis of Medullary Thyroid Carcinoma in Patients With Moderately Elevated Basal Calcitonin.

OBJECTIVE: Medullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs. METHODS: A total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses. RESULTS: A peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%. CONCLUSION: High-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified.

Ectopic thyroid tissue in adrenal gland, case report and review of literature.

Ectopic thyroid tissue is a rare pathological finding bellow the diaphragm and extremely rare finding is ectopic thyroid tissue in the adrenal gland (ETTAG). Thyroid tissue can be located anywhere along the way of embryological migration pathway of thyroglossal duct. In most cases of ectopic thyroid tissue, it is located in the neck. Here we present a case of 29 years old patient that was laparoscopically operated because of adrenal incidentaloma which showed 28 mm in maximal diameter on MRI. The patient had normal adrenal function. Pathohistological finding confirmed ETTAG. Follicular cells express TTF-1, Thyroglobulin, PAX8, and cytokeratin 7, and lack expression of calretinin. This is the 15th such case described in literature. Women are much more affected than men (14:1), and it usually presents in the fifth decade (mean age 49). In all cases ETTAG was composed of normal follicular cells, and C cells were not found. Review of the literature reveals that adrenal ectopic thyroid tissue is almost always cystic, and has distinctive pathologic features. The most important thing is that ETTAG must be distinguished from metastatic deposits from thyroid gland carcinoma. Our patient had normal thyroid function, without any nodules in thyroid gland. We report the youngest patient with ectopic thyroid tissue located in the adrenal gland.

Biochemical and clinical characteristics of patients with primary aldosteronism: Single centre experience.

BACKGROUND: Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. METHODS: Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). RESULTS: Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. CONCLUSIONS: Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity.

Elevated BANCR expression levels have different effects on papillary thyroid carcinoma progression depending on the presence of the BRAFV600E mutation.

INTRODUCTION: The role of BRAF-activated non-protein coding RNA (BANCR) in papillary thyroid carcinoma (PTC) is controversial, its clinical significance is unclear and no study has correlated the presence of the BRAFV600E mutation in PTC with BANCR expression. METHODS: BANCR levels in PTC and matched nonmalignant thyroid epithelial tissues from 85 patients were determined using quantitative RT-PCR. BRAFV600E was detected by mutant allele-specific PCR amplification. The results were correlated with clinicopathological characteristics of the patients. RESULTS: The presence of BRAFV600E associates with lower relative BANCR expression (RBE) in PTC (p = 0.008). RBE is down-regulated in BRAFV600E positive PTC, while it is unchanged or up-regulated in BRAFV600E negative PTC compared to the levels in paired nonmalignant tissue (p = 0.001). At the cut-off of 31.3%, sensitivity of fold change of BANCR for the presence of BRAFV600E is 68.0% and specificity is 67.2%. In BRAFV600E positive PTC up-regulated BANCR predicts lymph node metastasis (p = 0.001), while in BRAFV600E negative PTCs high RBE predicts thyroid capsule invasion (p = 0.028). CONCLUSIONS: Depending on the presence of BRAFV600E, elevated BANCR levels demonstrated different effects on lymphatic spreading and local PTC invasion. Therefore, BANCR could be a useful prognostic biomarker in risk stratification of PTC patients.

Correction to: Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter.

The original version of this article unfortunately contained a mistake.