Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression in Hyperthyroidism.

We aimed to analyze the potential influence of thyroid autoimmunity on visfatin/NAMPT serum concentration and its leukocyte expression in hyperthyroid patients. This is a single-center, cross-sectional study with consecutive enrollment. All patients with newly diagnosed overt hyperthyroidism in a course of Graves' disease or toxic nodular goiter were included in the study. They underwent physical examination, laboratory investigation, body composition analysis, and thyroid ultrasound. NAMPT mRNA leukocyte expressions were measured using RT-qPCR. Of the 173 patients, 95 were enrolled in further analysis [67 patients with Graves' disease (GD) and 28 with toxic nodular goiter (TNG)]. Control group consisted of 43 healthy volunteers adjusted for age, sex, and BMI. Higher NAMPT/visfatin serum concentration was found in patients with GD comparing with patients with TNG (p=0.03855). We found significant NAMPT leukocyte overexpression in GD patients (n=32) as compared to TNG patients (n=18) and euthyroid controls (n=24) (p=0.005965). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with NAMPT leukocyte expression, thyroid autoimmunity, age, HOMA-IR, and fat mass percentage (FM%). NAMPT leukocyte expression was related to thyroid autoimmunity, age, and TRAb levels. The stepwise multiple regression analysis revealed FM% and HOMA-IR as independent predictors of visfatin/NAMPT serum levels. In a separate stepwise multiple regression analysis, we confirmed the association between NAMPT leukocyte expression and TRAb levels. We found that fat mass percentage together with HOMA-IR are the most significant predictors of visfatin/NAMPT serum elevation in hyperthyroid patients.

Incidence of pituitary autoantibodies in idiopathic diabetes insipidus.

Diabetes insipidus is a disorder resulting from insufficient action of vasopressin (ADH) characterized by excretion of highly diluted urine in large amounts. Idiopathic diabetes insipidus is associated with the presence of both autoantibodies against ADH-secreting neurons and pituitary autoantibodies. The aim of the present study was to evaluate the occurrence of autoantibodies against the pituitary microsomal fraction. The study included 33 sera of diabetes insipidus patients and 10 control sera obtained from 10 healthy persons. In all patients the secretion of pituitary hormones and thyroid autoantibodies was assessed. Human pituitaries were obtained during autopsy and homogenized in 0.01 mol/l pH 7.4 phosphate buffer. In addition, for the autoantibody evaluation, the electrophoretic method of separation in polyacrylamide gel and western blot were employed. Among the 33 subjects, in 23 patients the presence of autoantibodies against the pituitary was shown. Sera of 15 patients reacted with the pituitary microsomal fraction protein of 55 kDa. In other cases, 10 sera reacted with the pituitary antigen of 67 kDa. In addition, 5 sera reacted with the 60 kDa antigen, 5 sera with 52 kDa protein, 3 sera with 105 kDa protein, 3 sera with the 97 kDa antigen and 2 sera with pituitary antigen of 92 kDa weight. In our study, based on the immunoblotting method, we observed that pituitary autoantibodies against 55, 60 and 67 kDa antigens occurred frequently.

Comparison of diagnostic yield of core-needle and fine-needle aspiration biopsies of thyroid lesions: Systematic review and meta-analysis.

OBJECTIVES: Thyroid nodular disease is one of the most commonly observed medical conditions. Cytological evaluation of the specimens obtained with fine-needle aspiration biopsy (FNAB) is the most accurate tool for selecting nodules which should be further surgically removed. A major limitation of this method is the high occurrence of non-diagnostic results. This indicates the need for improvement of the thyroid biopsy technique. The aim of this meta-analysis was to compare the diagnostic value of thyroid core-needle biopsies (CNBs) and FNABs. MATERIALS AND METHODS: PubMed/MEDLINE, Cochrane Library, Scopus, Cinahl, Academic Search Complete, Web of Knowledge, PubMed Central, PubMed Central Canada and Clinical Key databases were searched. Risk ratios (RRs) of non-diagnostic results were meta-analysed using the random-effects model. RESULTS: Eleven studies were included in the quantitative analysis. CNB yielded significantly more diagnostic results - the pooled risk ratio (RR) of gaining a non-diagnostic result was 0.27 (p<0.0001). For lesions with one previous non-diagnostic FNAB, RR was 0.22 (p<0.0001). CONCLUSIONS: CNB seems to be a valuable diagnostic technique yielding a higher proportion of diagnostic results than conventional FNAB. It is also significantly more effective in case of nodules with a prior non-diagnostic result of FNAB results than repeated FNABs. KEY POINTS: • Core-needle biopsy yields a higher proportion of diagnostic results than fine-needle biopsy. • Core-needle biopsies may decrease the amount of unnecessary thyroidectomies. • Probability of gaining non-diagnostic result using core-needle biopsy is almost four times lower.

[The impact of cannabinoids on the endocrine system].

Cannabinoids are naturally occurring compounds, derivatives of Indian hemp, in which tetrahydrocannabinol (THC) is the most important. Marijuana, hashish and hash oil are among those most commonly used in the group. Cannabinoids (marjhuana and hashish) have been used throughout recorded history as effective drugs in treating various diseases and conditions such as: malaria, hypertension, constipation, bronchial asthma, rheumatic pains, and as natural pain relief in labour and joint pains. Marijuana acts through cannabinoid receptors CB 1 and CB2. Both receptors inhibit cAMP accummulation (through Gi/o proteins) and stimulate mitrogen- activated protein kinase. CB1 rceptors are located in CNS and in adipose tissue, digestive tract, muscles, heart, lungs, liver, kidneys, gonads, prostate gland and other peripheral tissues. CB2 cannabinoid receptors are located in the peripheral nervous system (at the ends of peripheral nerves), and on the surfaces of the cells of the immunological system. The discovery of endogenous cannabinoids has contributed to a better understanding of their role in the regulation of the intake of food, energetic homeostasis and their significant influence on the endocrine system.

[Interaction between cigarette smoking and glucocorticoids therapy and therapeutic doses of radioiodine (131I) in patients with Graves' disease].

The present study evaluated the effects of smoking on the amount of therapeutic doses of radioiodine ((131)I) given to patients with Graves' disease (GB). The study also retrospectively analyzed the relationship between the onset of symptoms of thyroid ophthalmopathy (OT) after treatment with (131)I within 2 years and changes of TSHR-Abs levels, and the impact of prednisone administration before and after the therapy on OT development in both smoking and non-smoking patients. Materials and Methods: The study group included 116 patients, 97 women and 19 men, aged 28 ÷ 77 years (average 51 years) who were diagnosed with GB and treated with therapeutic doses of (131)I. Of the 116 patients treated, 85 patients were given a single dose of (131)I, whereas in 31 patients, due to recurrent hyperthyroidism, there was a need for a second dose of (131)I. In the group of 85 studied patients who received a single therapeutic dose of (131)I, 34 patients were smokers, including 27 women and 7 men, whereas in the group of 31 patients with recurrent hyperthyroidism who received repeated doses of 131I, 21 patients were smokers, 17 women and 4 men. Patients qualified for the therapy with (131)I and diagnosed with mild OT, were given prednisone, administered orally with an initial dose of 0.4 - 0.5 mg/kg daily tapering within 4-6 weeks. Results: The results of the study demonstrated that there was a statistically significant relationship (p<0.05) between cigarette smoking and the number of administered therapeutic doses of (131)I in patients with GD. Smoking patients needed to be given the second therapeutic dose of (131)I more frequently. The relationship between the onset of symptoms of OT in patients with GD and the TSHRAb in serum within two years after (131)I administration was highly significant (p<0.0001). The results obtained in our study showed that efficacy of therapy was lower in smokers with GD when compared with non-smokers Since the increased titer of TSHR-Ab was associated with higher risk of OT development, especially in smokers, its routine measurement after (131)I administration could be considered in all treated patients with GD. Steroid prophylaxis should be recommended for each smoking GD patient with mild OT qualified for (131)I therapy.

The role of antithyroglobulin, antiperoxidase and anti-TSH receptor autoantibodies in amiodarone-induced thyrotoxicosis and amiodarone-induced hypothyroidism (A two-center study).

OBJECTIVE: It has been reported that patients experiencing side effects of amiodarone (AM) therapy, such as amiodarone-induced thyrotoxocosis (AIT) or amiodarone-induced hypothyroidism (AIH), have changes in serum concentrations of anti-TSH receptor (TSHR), antithyroglobulin (Tg), and antiperoxidase (TPO) autoantibodies (Abs). The purpose of our study was to identify and analyze the changes in levels of listed antibodies in patients with several thyroid disorders. METHODS: 280 patients from two centers in Poland were included. Titers of TSHR-Abs, TPO-Abs and Tg-Abs were analyzed retrospectively in the following groups of patients: A - euthyroid patients with a history of hyperthyroidism prior to re-administration of AM; B - patients with AIT who discontinued the AM therapy; C - patients with AIT chronically treated with AM; D - hypothyroid patients. RESULTS: Serum Tg-Abs were not elevated in any of the studied groups. However, there were significant differences between A and B and also D and other groups (p<0.05). TPO-Abs titers were not elevated in most cases, there were no significant differences between groups. The serum titers of TSHR-Abs were not elevated in any group. We found statistically significant differences between B and D, C and other groups (p<0.05). CONCLUSIONS: Regardless of the statistically significant differences observed for Tg-Abs and TSHR-Abs levels, this observation have a limited clinical applicability. In almost all cases we observed normal to slightly increased titers of TPO-Abs, Tg-Abs, TSHR-Abs. Discontinuation or continuation of AM therapy had no influence on autoantibody titers. Furthermore, we found it impossible to differentiate between the type I and II of AIT based on autoantibody titers.

Core needle biopsy of thyroid nodules - evaluation of diagnostic utility and pain experience.

OBJECTIVE: A crucial problem in the non-operative diagnosis of thyroid nodules is the significant amount of non-diagnostic biopsies. This is a challenge for practicing endocrinologists especially when the results of the repeated biopsies remain non-diagnostic. The lack of a concrete preoperative diagnosis may result in unnecessary thyroidectomies in patients. Alternatively, it may also lead to the delayed diagnosis of cancer. One method of biopsy specimen acquisition that could potentially increase the diagnostic accuracy of thyroid biopsies is the application of core-needles. The aim of the study was to compare the diagnostic value and patient tolerability of core-needle aspiration biopsies (CNAB) with fine-needle aspiration biopsies (FNAB). PATIENTS AND METHODS: The study included patients with thyroid nodular goiter in whom previous conventional FNAB yielded non-diagnostic results. CNABs were performed using 22G core-needles. The control group consisted of patients undergoing conventional FNAB with 25G fine-needles. Pain during core-needle biopsies of thyroid nodules was assessed using the 10-point visual analog scale. RESULTS: There were a total of 30 lesions in 26 patients undergoing CNAB (22 women, 4 men, mean age 48.3) and a total of 59 lesions in 40 patients undergoing FNAB (34 women, 6 men, mean age 57.3). 56.6% of CNABs and 50.8% of FNABs were diagnostic (p=0.60). When assessing pain via the visual analog scale, the median score for biopsies performed with core-needles was four. 60.0% of patients considered the pain of core-needle aspiration biopsies to be similar to the pain experienced during the previous conventional fine-needle aspiration biopsies, while 40% of patients claimed that the pain was more intense. CONCLUSIONS: CNAB did not prove to be superior to FNAB. Despite the larger needle gauge used during core-needle biopsies, the patients' tolerability was comparable to conventional fine-needle biopsies.

Amiodarone-induced thyrotoxicosis in a case of Eisenmenger's syndrome.

Eisenmenger's syndrome is a condition due to any congenital heart defect with an intracardiac left-to-right communication that leads to pulmonary hypertension with reversed right-to-left blood flow and secondary cyanosis. The main complications of Eisenmenger's syndrome are heart failure and arrhythmias. Amiodarone, the drug of choice for arrhythmia treatment in such patients, can cause a number of complications, including amiodarone induced thyrotoxicosis (AIT). Hereby, we present a 41-year-old patient with Eisenmenger's syndrome who developed AIT and was successfully treated with radioactive iodine therapy. The patient had an accompanying heart failure and had been treated with amiodarone due to chronic atrial fibrillation. Twenty months later he developed an AIT for which was treated with 814 MBq (22 mCi) radioactive iodine. Since 7 weeks later only a slight decline in thyroid hormones was observed, the patient was received a transient treatment with methimazole, which had to be withdrawn soon due to severe leucopenia. Because of the need to maintain amiodarone, a second ablative radioactive iodine dose was administered leading to complete clinical remission. In conclusion, this case demonstrates that even though amiodarone reduces iodine uptake to a very low level, the therapy with radioactive iodine can be still effective if it is given in a repeated dose to patients who require continuation of amiodarone.

Risk of neoplasms in acromegaly.

Acromegaly is a chronic disease caused by the excessive secretion of growth hormone (GH), and as a result, of insulin-like growth factor-1 (IGF-1). Untreated, the condition reduces the patients' life expectancy and leads to a series of complications, among which an increased risk of carcinogenesis is considered most important. This paper is an analysis of the publications on the issue of the formation of neoplasms, both malignant and benign, in acromegalic patients. Although the influence of acromegaly on carcinogenesis remains controversial, a number of studies indicate that the frequency of developing tumors in this patient group is higher. Moreover, numerous publications particularly stress the increased risk of developing neoplasms in patients who had been untreated for a long period of time and show elevated levels of GH and IGF-1. Consequently, a quick diagnosis and the implementation of effective treatment play a key role in the management of this disease.

Determination of neuron-specific enolase in patients with midgut-type tumour treated with somatostatin analogues.

INTRODUCTION: The biochemical diagnosis of neuroendocrine tumours (NETs) uses assays of specific and nonspecific markers. Nonspecific markers include, among others, neuron-specific enolase (NSE). The aim of this study was to evaluate NSE in patients with midgut type tumours treated with somatostatin analogues. MATERIAL AND METHODS: The study group of patients with NETs of the small intestine included 41 patients. Grade G1 was found in 19 cases, while G2 was seen in the remaining 22 cases. Liver metastases were found in all patients studied. The examined group of patients was treated with somatostatin analogues receiving octreotide LAR at a dose of 30 mg. The control of biochemical parameters was performed every 3 months and imaging examinations every 6 months. The Immuno-Biological Laboratories kit was used for determination of NSE concentration, where reference values were 12.5-25 ng/mL. RESULTS: In the G1 group of patients, the median value of NSE concentration was 134.67 ng/mL, while in the G2 group, the value was 234.55 ng/mL and was significantly higher than in the G1 group (p = 0.003). In the determination of NSE concentration values according to the degree of liver involvement, in the group of patients with 10% liver involvement, the median value of NSE concentration was 143.21 ng/mL, while in the group with 25% liver involvement, the value was 251.82 ng/mL (p < 0.001). In the analysis of NSE concentration assessment in patients with disease progression, the median value was 234.65 ng/mL compared to the group with disease stabilization, where the median NSE value was significantly lower and amounted to 136.27 ng/mL (p < 0.001). CONCLUSIONS: In our study, we observed that NSE concentration values were significantly higher among patients with NET midgut type tumour with histological grade G2 and in patients with 25% liver involvement and progression of the disease process.

Sonographic Features Differentiating Follicular Thyroid Cancer from Follicular Adenoma-A Meta-Analysis.

Certain ultrasound features are associated with an increased risk of thyroid malignancy. However, they were studied mainly in papillary thyroid cancers (PTCs); these results cannot be simply extrapolated for the differentiation of follicular thyroid adenomas and cancers (FTAs and FTCs). The aim of our study was to perform a meta-analysis to identify sonographic features suggesting malignancy in the case of follicular lesions, potentially differentiating FTA and FTC. We searched thirteen databases from January 2006 to December 2020 to find all relevant, full-text journal articles written in English. Analyses assessed the accuracy of malignancy detection in case of follicular lesions, potentially differentiating FTA and FTC included the odds ratio (OR), sensitivity, specificity, positive and negative predictive values. A random-effects model was used to summarize collected data. Twenty studies describing sonographic features of 10,215 nodules met the inclusion criteria. The highest overall ORs to increase the risk of malignancy were calculated for tumor protrusion (OR = 10.19; 95% confidence interval: 2.62-39.71), microcalcifications or mixed type of calcifications (coexisting micro and macrocalcifications): 6.09 (3.22-11.50), irregular margins: 5.11 (2.90-8.99), marked hypoechogenicity: 4.59 (3.23-6.54), and irregular shape: 3.6 (1.19-10.92). The most crucial feature associated with an increased risk of FTC is capsule protrusion, followed by the presence of calcifications, irrespectively of their type.

Higher EU-TIRADS-Score Correlated with BRAF V600E Positivity in the Early Stage of Papillary Thyroid Carcinoma.

The data demonstrating a correlation between sonographic markers of malignancy of thyroid cancer (TC) and its genetic status are scarce. This study aimed to assess whether the addition of genetic analysis at the preoperative step of TC patients' stratification could aid their clinical management. The material consisted of formalin-fixed paraffin-embedded tumor fragments of 49 patients who underwent thyroidectomy during the early stages of papillary TC (PTC). Tumor DNA and RNA were subjected to next-generation sequencing (NGS) on Ion Proton using the Oncomine™ Comprehensive Assay panel. We observed a significant correlation between BRAF V600E and a higher EU-TIRADS score (p-value = 0.02) with a correlation between hypoechogenicity and taller-than-wide tumor shape in analysed patients. There were no other significant associations between the identified genetic variants and other clinicopathological features. For TC patient's stratification, a strong suspicion of BRAF V600E negativity in preoperative management of TC patients could limit the over-treatment of asymptomatic, very low-risk, indolent disease and leave room for active surveillance.

Is low radioiodine uptake a contraindication to radioiodine therapy in patients with benign thyroid disease?

BACKGROUND: Radioiodine therapy (131I) is a standard procedure in the treatment of hyperthyroidism in the course of Graves' disease or toxic nodules. However, the use of 131I in patients with low radioiodine uptake (RAIU) may be controversial. OBJECTIVES: To determine the influence of lithium carbonate (Li) on iodine kinetics. MATERIAL AND METHODS: Patients with hyperthyroidism and low RAIU (< 30%) were divided into 2 groups: a Li(-) group of 305 patients not receiving Li adjuvant therapy and a Li(+) group of 264 patients receiving adjuvant therapy. The serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone (TSH) were assessed at baseline, 24 h, 48 h, 72 h and 96 h, and 1, 6 and 12 months after 131I therapy. The RAIU was assessed after 5 h, 24 h, 48 h, 72 h, and 96 h. RESULTS: Levels of fT3 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 48 h, 72 h, 96 h and 1 month, and did not differ significantly after 24 h, 6 months and 12 months. Levels of fT4 in the Li(+) group compared to the Li(-) group were significantly higher at baseline, lower after 24 h, 48 h, 72 h, 96 h and 1 month, and not differ significantly after 6 and 12 months. The RAIU in the hyperthyroidism Li(-) and Li(+) groups, respectively, was 11.9 ±5.6% compared to 23.9 ±10.1% (p < 0.001) after 5 h; 25.9 ±8.3% compared to 40.5 ±12.4% (p < 0.05) after 24 h; 7.8 ±8.1% compared to 40.9 ±13.7% (p < 0.05) after 48 h; 26.2 ±10.2% compared to 39.5 ±11.2% (p < 0.01) after 72 h; and 24.7 ±7.1% compared to 37.4 ±10.1% (p < 0.01) after 96 h. CONCLUSIONS: Adjuvant therapy with Li in patients with hyperthyroidism caused a significant increase in RAIU and positive changes in the fT3 and fT4 profiles. The use of lithium carbonate prior to the inclusion of 131I in hyperthyroid patients with low RAIU should be considered.

Radioiodine therapy and Graves' disease - Myths and reality.

INTRODUCTION: Autoimmune reactions in Graves' disease (GD) occur not only in the thyroid gland, but also in the orbital connective tissue, eyelids, extraocular muscles. The occurrence of orbitopathy in the course of GD is influenced by environmental factors, e.g. cigarette smoking. OBJECTIVES: The aim of the study was to analyze the effect of cigarette smoking on the efficacy of activity of radioiodine(131I) therapy in patients with GD. We also studied the influence of cigarette smoking and the efficacy of prednisone prophylaxis on the risk of thyroid-associated ophthalmopathy (TAO) development after radioiodine therapy (RIT) during two years of follow-up. PATIENTS AND METHODS: Medical records of hyperthyroid patients treated with radioiodine had been included. Patients were scheduled to visit outpatient clinics at baseline and 1, 3, 6, 9, 12, 18, and 24 months after RIT. RESULTS: The studied group consisted of 336 patients (274 women, 62 men) diagnosed with GD and treated with RIT; 130 patients received second therapeutic dose of 131I due to recurrent hyperthyroidism. Among all studied patients, 220 (65.5%) were smokers and 116 (34.5%) non-smokers. In the group of smokers 115 (52.2%) of patients received single RIT, 105 (47.8%) received second dose of RAI due to recurrent hyperthyroidism. In non-smokers 91 (78.6%) received single activity of RAI, while 25 (21.4%) patients required second RIT due to recurrent hyperthyroidism. The ophthalmic symptoms in the group of smokers after RIT were less frequent, if the patient received preventative treatment in the form of oral prednisone (P = 0.0088). CONCLUSIONS: The results of our study suggest that cigarette smoking reduces the efficacy of treatment with 131I in patients with GD. The study also confirmed the effectiveness of steroid prophylaxis against TAO development or exacerbation after RIT.

S-Detect Software vs. EU-TIRADS Classification: A Dual-Center Validation of Diagnostic Performance in Differentiation of Thyroid Nodules.

Computer-aided diagnosis (CAD) and other risk stratification systems may improve ultrasound image interpretation. This prospective study aimed to compare the diagnostic performance of CAD and the European Thyroid Imaging Reporting and Data System (EU-TIRADS) classification applied by physicians with S-Detect 2 software CAD based on Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and combinations of both methods (MODELs 1 to 5). In all, 133 nodules from 88 patients referred to thyroidectomy with available histopathology or with unambiguous results of cytology were included. The S-Detect system, EU-TIRADS, and mixed MODELs 1-5 for the diagnosis of thyroid cancer showed a sensitivity of 89.4%, 90.9%, 84.9%, 95.5%, 93.9%, 78.9% and 93.9%; a specificity of 80.6%, 61.2%, 88.1%, 53.7%, 73.1%, 89.6% and 80.6%; a positive predictive value of 81.9%, 69.8%, 87.5%, 67%, 77.5%, 88.1% and 82.7%; a negative predictive value of 88.5%, 87.2%, 85.5%, 92.3%, 92.5%, 81.1% and 93.1%; and an accuracy of 85%, 75.9%, 86.5%, 74.4%, 83.5%, 84.2%, and 87.2%, respectively. Comparison showed superiority of the similar MODELs 1 and 5 over other mixed models as well as EU-TIRADS and S-Detect used alone (p-value < 0.05). S-Detect software is characterized with high sensitivity and good specificity, whereas EU-TIRADS has high sensitivity, but rather low specificity. The best diagnostic performance in malignant thyroid nodule (TN) risk stratification was obtained for the combined model of S-Detect ("possibly malignant" nodule) and simultaneously obtaining 4 or 5 points (MODEL 1) or exactly 5 points (MODEL 5) on the EU-TIRADS scale.

Health-Related Complications of Acromegaly-Risk of Malignant Neoplasms.

The issue of increased risk of benign and malignant neoplasms in patients with acromegaly remains the topic of debate from many years and was addressed by numerous studies. Many of them have shown increase in the cancer incidence. Among particular types of malignancies, thyroid, colorectal, and breast cancer are most commonly indicated as associated with acromegaly. Single reports denoted increase in prevalence of neoplasms of other organs such as kidney, bone or central nervous system. Cardiovascular and respiratory tract disorders were traditionally consider as main causes of mortality in acromegalic patients, accounting for about 60 and 25% of deaths, respectively. However, according to a number of studies published over the current decade cancer became the most important cause of deaths. Aim of the current article was to review the literature concerning the risk of malignant neoplasms in acromegaly and its clinical implications.

Klotho expression and nodal involvement as predictive factors for large cell lung carcinoma.

INTRODUCTION: Klotho has been recently described as a carcinogenesis suppressor. Large cell neuroendocrine lung carcinoma (LCNEC) is a rare, highly malignant neoplasm. In the light of increasing incidence of neuroendocrine tumours, biomarkers predicting survival are needed. We consider that Klotho might be one. MATERIAL AND METHODS: We analysed records of all patients diagnosed with LCNEC, atypical carcinoid and typical carcinoid operated on in our institution between 2007 and 2015. Initially, we found 134 cases. Forty-six specimens were unattainable and thus excluded from research. All patients diagnosed with LCNEC according to the WHO classification were included in the study. Immunohistochemical staining for Klotho was performed. We retrospectively reviewed patient charts and analysed multiple variables. RESULTS: Positive staining for Klotho was present in 36 tissue specimens, while 12 patients were Klotho-negative. Survival length was significantly higher in Klotho-positive cases (p = 0.024), while advanced nodal status (N1 and N2) represented a marker of poor outcome (p = 0.011). In multivariate analysis, both Klotho presence (p = 0.015; HR = 0.37; 95% CI: 0.17-0.86) and nodal involvement (p = 0.007; HR = 3.04; 95% CI: 1.37-6.82) were independent prognostic factors. Tumour vessel invasion and visceral pleura infiltration were not associated with worse treatment results. Klotho presence predicted a favourable prognosis in these groups (p = 0.018; p = 0.007). CONCLUSIONS: Our results suggest that Klotho might be a positive factor for predicting survival in LCNEC and nodal involvement a negative one. Thus, these two markers may assist in the selection of subjects with unfavourable prognosis and to personalise therapy regimens.

Histopathological Verification of the Diagnostic Performance of the EU-TIRADS Classification of Thyroid Nodules-Results of a Multicenter Study Performed in a Previously Iodine-Deficient Region.

BACKGROUND: To validate the European Thyroid Imaging and Reporting Data System EU-TIRADS classification in a multi-institutional database of thyroid nodules by analyzing the obtained scores and histopathology results. METHODS: A total of 842 thyroid lesions (613 benign, 229 malignant) were identified in 428 patients (mean age 62.7 years) and scored according to EU-TIRADS, using ultrasound examination. In all tumors, histopathological verification was performed. RESULTS: In EU-TIRADS 2 (154 nodules) all nodules were benign; in EU-TIRADS 3, only 3/93 malignancies were identified. In EU-TIRADS 4, 12/103 were malignant, and in EU-TIRADS 5 (278 benign vs. 214 malignant). The malignant nodules that would not have qualified for biopsy were: EU-TIRADS 3, 2/3 (67%) malignancies were <20 mm, in EU-TIRADS 4, 7/12 (58%) were <15 mm. In EU-TIRADS 5, 72/214 (34%) were <10 mm; in total, 81/229 (36%) malignant lesions would have been missed. The cutoff between EU-TIRADS 3/4 had sensitivity of 100%, specificity of 25.1%. Using cutoff for EU-TIRADS 5, 93.4%, 54.6%, respectively. CONCLUSION: The application of EU-TIRADS guidelines allowed us to achieve moderate specificity. The vast majority of malignancies in EU-TIRADS 3, 4, and 5 would not have been recommended for biopsy because having a smaller size than that proposed classification.

The role of immunohistochemical examination in diagnosis of papillary thyroid cancer in struma ovarii.

INTRODUCTION: Struma ovarii (SO) is a monodermal teratoma in which thyroid tissue comprises more than 50% of the tumour. Papillary thyroid cancer (PTC) in SO is a rare finding, as only 5% of SO cases undergo malignant transformation. Malignant SO is usually asymptomatic and infrequently diagnosed preoperatively. Because of its rarity, there is no consensus about diagnosis and management, while treatment and follow-up procedures are not clearly established. MATERIAL AND METHODS: Herewith, we report two cases of PTC in SO. The first patient was a 25-year-old woman diagnosed with bilateral ovarian tumours. The second patient, 19-year-old woman, presented with unilateral ovarian mass. Both patients were qualified for surgical excision of the tumours. Histopathological specimens underwent both conventional histopathological assessment and immunohistochemical staining. RESULTS: In the first patient histopathology revealed SO with two foci of PTC. Immunohistochemically a positive expression of CK7, CK19, p63 and thyroglobulin (Tg) confirmed the diagnosis. She underwent total thyroidectomy in 2016 in order to enable ablative radioiodine therapy and facilitate further thyroglobulin monitoring. Unfortunately, the patient was lost from follow-up. In the second patient, histopathological diagnosis was follicular variant of PTC in SO. Postoperatively, a pelvic CT revealed osteolytic lesion 6 cm in size, being a metastatic change. The patient underwent unilateral ovariectomy, total thyroidectomy and multiple cycles of radioiodine therapy. Currently, 9 years following the diagnosis, the patient achieved disease remission. CONCLUSIONS: PTC in SO still remains a diagnostic and therapeutic challenge. Immunostaining for CK7, CK19, p63 and Tg might be helpful in histopathological diagnosis. The decision on the need of total thyroidectomy and radioiodine therapy should be made individually. However, thyroid remnant ablation increases the sensitivity and specificity of follow-up testing using serum Tg level as a tumour marker.

Shear wave elastography in the diagnostics of parathyroid adenomas-new application of the method.

PURPOSE: Shear wave elastography (SWE) was described as valuable tool in the diagnostics of distinct types of thyroid lesions, thyroiditis and several other non-thyroidal conditions, such as liver inflammation and fibrosis or diagnostics of breast lesions. The aim of the current study was to assess the appearance of parathyroid adenomas in SWE and to check prospectively if SWE can be valuable additional tool in the diagnostics of pathologically enlarged parathyroids. METHODS: Patients with parathyroid adenomas confirmed by histopathology were included. Subjects with benign thyroid lesions were enrolled to the control group. Elasticity of parathyroid adenomas and benign thyroid nodules was measured and compared. RESULTS: Sixty five patients with parathyroid adenomas and 35 patients with 51 benign thyroid nodules were included. Parathyroid adenomas where significantly more elastic than benign thyroid nodules-mean elasticity of the lesion was 5.2 ± 7.2 vs. 24.3 ± 33.8 kPa, respectively. Relative mean elasticity (in comparison with surrounding thyroid tissue) was 0.30 ± 0.36 and 2.8 ± 3.9, respectively. CONCLUSIONS: SWE can be useful tool in the diagnostics of parathyroid adenomas. Enlarged parathyroids are significantly more elastic than benign thyroid lesions. Low elasticity of the lesion constitutes feature with high negative prognostic value, allowing for reliable exclusion of suspicion of parathyroid adenomas.