The relationship between thyroid and human-associated microbiota: A systematic review of reviews.

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

Experimental and Numerical Analysis of a Pd-Ag Membrane Unit for Hydrogen Isotope Recovery in a Solid Blanket.

The interest of the fusion community in Pd-Ag membranes has grown in the last decades due to the high value of hydrogen permeability and the possibility of continuous operation, making it a promising technology when a gaseous stream of hydrogen isotopes must be recovered and separated from other impurities. This is the case of the Tritium Conditioning System (TCS) of the European fusion power plant demonstrator, called DEMO. This paper presents an experimental and numerical activity aimed at (i) assessing the Pd-Ag permeator performance under TCS-relevant conditions, (ii) validating a numerical tool for scale-up purposes, and (iii) carrying out a preliminary design of a TCS based on Pd-Ag membranes. Experiments were performed by feeding the membrane with a He-H2 gas mixture in a specific feed flow rate ranging from 85.4 to 427.2 mol h-1 m-2. A satisfactory agreement between experiments and simulations was obtained over a wide range of compositions, showing a root mean squared relative error of 2.3%. The experiments also recognized the Pd-Ag permeator as a promising technology for the DEMO TCS under the identified conditions. The scale-up procedure ended with a preliminary sizing of the system, relying on multi-tube permeators with an overall number ranging between 150 and 80 membranes in lengths of 500 and 1000 mm each.

Thyroid metabolism and supplementation: A review framed in sports environment.

OBJECTIVES: This paper aimed to consider those features that may suggest a link between thyroid hormones pharmacology and athletes' health based on current consumption trends in a population of athletes. METHODS: Methods used were observation, description, and synthesis, mainly. Among the documents reviewed were books, scientific articles, and review articles peer-reviewed. The review covered sources published in the period 1961 to 2021. Only references with a traceable origin were accepted (DOI numbering, ISSN, and ISBN, as well as peer-reviewed journals). The data on the consumption of thyroid hormones derivatives were extracted from the Doping Control Forms of athlete samples received at Laboratorio Antidoping FMSI of Rome from 2017 to 2021. RESULTS: An overview of the biosynthesis, pharmacology, and metabolism of thyroid hormones, including thyronamines and thyronacetic acids, was presented. Likewise, a summary is presented on the relationship between thyroid hormones and ethnic and gender differences, their physiology in sport, and the reasons why their use could be considered attractive for athletes. CONCLUSION: Today, thyroid hormones are not listed as a prohibited substance by the World Anti-Doping Agency. However, several requests to include levothyroxine on the prohibited list are documented. The observation that the number of athletes taking thyroid hormones is growing, particularly in sports such as cycling, triathlons, and skating, should prompt an update on this topic.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Fibrosis-4 Index vs Nonalcoholic Fatty Liver Disease Fibrosis Score in Identifying Advanced Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

INTRODUCTION: In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. METHODS: Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. RESULTS: Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. DISCUSSION: This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

Performance of Fatty Liver Index in Identifying Non-Alcoholic Fatty Liver Disease in Population Studies. A Meta-Analysis.

BACKGROUND: Fatty liver index (FLI) is a non-invasive tool used to stratify the risk of non-alcoholic fatty liver disease (NAFLD) in population studies; whether it can be used to exclude or diagnose this disorder is unclear. We conducted a meta-analysis to assess the prevalence of NAFLD in each FLI class and the performance of FLI in detecting NAFLD. METHODS: Four databases were searched until January 2021 (CRD42021231367). Original articles included were those reporting the performance of FLI and adopting ultrasound, computed tomography, or magnetic resonance as a reference standard. The numbers of subjects with NAFLD in FLI classes <30, 30-60, and ≥60, and the numbers of subjects classified as true/false positive/negative when adopting 30 and 60 as cut-offs were extracted. A random-effects model was used for pooling data. RESULTS: Ten studies were included, evaluating 27,221 subjects without secondary causes of fatty liver disease. The prevalence of NAFLD in the three FLI classes was 14%, 42%, and 67%. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive results, likelihood ratio for negative results, and diagnostic odds ratio were 81%, 65%, 53%, 84%, 2.3, 0.3, and 7.8 for the lower cut-off and 44%, 90%, 67%, 76%, 4.3, 0.6, and 7.3 for the higher cut-off, respectively. A similar performance was generally found in studies adopting ultrasound versus other imaging modalities. CONCLUSIONS: FLI showed an adequate performance in stratifying the risk of NAFLD. However, it showed only weak evidence of a discriminatory performance in excluding or diagnosing this disorder.

The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis.

Thyroid imaging reporting and data systems (TIRADS) are used to stratify the malignancy risk of thyroid nodule by ultrasound (US) examination. We conducted a meta-analysis to evaluate the pooled cancer prevalence and the relative prevalence of papillary, medullary, follicular thyroid cancer (PTC, MTC, and FTC) and other malignancies among nodules included in studies evaluating their performance. Four databases were searched until February 2020. Original articles with at least 1000 nodules, evaluating the performance of at least one TIRADS among AACE/ACE/AME, ACR-TIRADS, ATA, EU-TIRADS, or K-TIRADS, and reporting data on the histological diagnosis of malignant lesions were included. The number of malignant nodules, PTC, FTC, MTC and other malignancies in each study was extracted. For statistical pooling of data, a random-effects model was used. Nine studies were included, evaluating 19,494 thyroid nodules. The overall prevalence of malignancy was 34% (95%CI 21 to 49). Among 6162 histologically proven malignancies, the prevalence of PTC, FTC, MTC and other malignancies was 95%, 2%, 1%, and 1%, respectively. A high heterogeneity was found for all the outcomes. A limited number of studies generally conducted using a retrospective design was found, with possible selection bias. Acknowledging this limitation, TIRADSs should be regarded as accurate tools to diagnose PTC only. Proposed patterns and/or cut-offs should be revised and other strategies considered to improve their performance in the assessment of FTC, MTC and other malignancies.

Effects of transdermal administration of testosterone gel on the urinary steroid profile in hypogonadal men: Implications in antidoping analysis.

Testosterone is one of the most abused pseudo-endogenous anabolic steroids in sport doping. The current method adopted to detect the abuse of testosterone and other pseudo-endogenous steroids (endogenous steroids when administered exogenously) is first based on the longitudinal monitoring of several urinary biomarkers, which constitute the so called "steroidal module" of the Athlete Biological Passport (ABP): atypical samples undergo a confirmation analysis based on the measurement of the 13C/12C isotopic ratio of selected target compounds, to distinguish their endogenous or exogenous origin. At the same time, testosterone administration can be allowed in athletes diagnosed with hypogonadism, provided they are granted a therapeutic use exemption by the relevant medical authority. In this pilot study we have investigated whether the approach based on the preliminary determination of the urinary steroid profile, in the format considered in the steroidal module of the ABP, also integrated with the inclusion of the sulfo-conjugates and of additional target steroids, can retain its validity also in the case of hypogonadal athletes. We have studied the effects of a single low dose (40 mg) of testosterone gel (T-gel) on the urinary concentration of the markers of steroidal module of the ABP, as well as on some additional steroid markers. The study was based on the analysis of urinary samples from 19 non-hospitalized hypogonadal men, 10 of them with late-onset hypogonadism (LOH), collected before, after 4 h and after 24 h the transdermal self-administration of 40 mg of T-gel. None of the patient had any co-morbidities possibly affecting the urinary excretion of the steroidal markers. The steroidal markers were quantified by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) after the enzymatic hydrolysis of the respective glucuro-conjugates and the chemical hydrolysis of the respective sulfo-conjugates. Targeted GC-MS/MS analysis was carried out operating in electron impact (EI) ionization mode, with acquisition in multiple reaction monitoring (MRM) mode. Our preliminary results show that, as expected, the treatment with T-gel leads, in all hypogonadal men, to an increase of the urinary concentration of the glucuro-conjugate metabolites of testosterone and its main metabolites, with special relevance to those with 5α-reduction. Furthermore, samples collected from non-LOH hypogonadal men showed an increase also in the levels of epitestosterone glucuronide, testosterone sulfate and epitestosterone sulfate. Apart from their biochemical and pharmacological relevance, these outcomes could be leveraged to refine the analytical strategy currently followed in the antidoping field for the analysis of the urinary steroidal markers, with potential implications also in other forensic and/or clinical investigations.

The Sentiment Analysis of Tweets as a New Tool to Measure Public Perception of Male Erectile and Ejaculatory Dysfunctions.

INTRODUCTION: Twitter is a social network based on "tweets," short messages of up to 280 characters. Social media has been investigated in health care research to ascertain positive or negative feelings associated with several conditions but never in sexual medicine. AIM: To assess perceptions related to erectile dysfunction (ED) and premature ejaculation (PE) among Twitter users. METHODS: Data collection was performed on a daily basis between May 24-October 9, 2018 (138 days) via an automated script. Data collection was then performed after data cleaning. The statistical software R and the rtweet packages were used in both phases. RESULTS: We collected 11,000 unique tweets for PE and 30,546 unique tweets for ED. After data cleaning, we analyzed 7,020 tweets on PE and 22,648 tweets on ED by analyzing the most recurring words and the clusters describing word associations. The most popular words for ED were "Treatment," "Health," and "Viagra," whereas "Sex," "Sexual," and "Cure" were the top 3 for PE. Word clusters suggest the presence of some recurring themes, such as medical terms being grouped together. Additionally, tweets reflect the general feelings triggered by specific events, such as pieces of news pertaining to sexual dysfunctions. CLINICAL IMPLICATIONS: Tweets on sexual dysfunctions are posted every day, with more tweets on ED than on PE. Treatment is among the chief topics discussed for both conditions, although health concerns differ between PE and DE tweets. STRENGTH AND LIMITATIONS: This is the first analysis conducted on Tweets in the field of andrology and sexual medicine. A significant number of tweets were collected and analyzed. However, quantitative assessment of the sentiment was not feasible. CONCLUSION: Sexual dysfunctions are openly discussed on social media, and Twitter analysis could help understand the needs and interests of the general population on these themes. Sansone A, Cignarelli A, Ciocca G, et al. The Sentiment Analysis of Tweets as a New Tool to Measure Public Perception of Male Erectile and Ejaculatory Dysfunctions. Sex Med 2019;7:464-471.

Specific and Non-Specific Biomarkers in Neuroendocrine Gastroenteropancreatic Tumors.

The diagnosis of neuroendocrine tumors (NETs) is a challenging task: Symptoms are rarely specific, and clinical manifestations are often evident only when metastases are already present. However, several bioactive substances secreted by NETs can be included for diagnostic, prognostic, and predictive purposes. Expression of these substances differs between different NETs according to the tumor hormone production. Gastroenteropancreatic (GEP) NETs originate from the diffuse neuroendocrine system of the gastrointestinal tract and pancreatic islets cells: These tumors may produce many non-specific and specific substances, such as chromogranin A, insulin, gastrin, glucagon, and serotonin, which shape the clinical manifestations of the NETs. To provide an up-to-date reference concerning the different biomarkers, as well as their main limitations, we reviewed and summarized existing literature.

Endocrine Disrupting Chemicals: Effects on Endocrine Glands.

In recent years, endocrine disrupting chemicals have gained interest in human physiopathology and more and more studies aimed to explain how these chemicals compounds affect endocrine system. In human populations, the majority of the studies point toward an association between exposure to endocrine disrupting chemicals and the disorders affecting endocrine axis. A great number of endocrine disrupting chemicals seem to be able to interfere with the physiology of hypothalamus-pituitary-gonadal axis; however, every endocrine axis may be a target for each EDCs and their action is not limited to a single axis or organ. Several compounds may also have a negative impact on energy metabolic homeostasis altering adipose tissue and promoting obesity, metabolic syndrome, and diabetes. Different mechanism have been proposed to explain these associations but their complexity together with the degree of occupational or environmental exposure, the low standardization of the studies, and the presence of confounding factors have prevented to establish causal relationship between the endocrine disorders and exposure to specific toxicants so far. This manuscript aims to review the state of art of scientific literature regarding the effects of endocrine-disrupting chemicals (EDCs) on endocrine system.

Effects of percutaneous varicocele repair on testicular volume: results from a 12-month follow-up.

Varicocele is a common finding in men. Varicocele correction has been advocated for young patients with testicular hypotrophy, but there is a lack of morphofunctional follow-up data. We assessed whether percutaneous treatment of left varicocele is associated with testicular "catch-up growth" in the following 12 months by retrospectively reviewing data from an electronic database of 10 656 patients followed up in our clinic between 2006 and 2016. We selected all young adults (<35 years) with left varicocele who underwent percutaneous treatment, had a minimum of 12 months' ultrasound imaging follow-up, and had no other conditions affecting testicular volume. One hundred and fourteen men (mean±standard deviation [s.d.] of age: 22.8 ± 5.4 years) met the inclusion and exclusion criteria. Left testicular hypotrophy (LTH), defined as a ≥20% difference between left and right testicular volume at baseline, was observed in 26 (22.8%) men. Participants with LTH (mean±s.d.: 14.5 ± 2.7 ml) had lower baseline testicular volume compared to those without LTH (mean±s.d.: 15.7 ± 3.8 ml; P = 0.032). Repeated measures mixed models showed a significant interaction between LTH and time posttreatment when correcting for baseline left testicular volume (ß = 0.114, 95% confidence interval [CI]: 0.018-0.210, P = 0.020), resulting in a catch-up growth of up to 1.37 ml per year (95% CI: 0.221-2.516). Age at intervention was also associated with reduced testicular volume (-0.072 ml per year, 95% CI: -0.135--0.009; P = 0.024). Percutaneous treatment of left varicocele in young adults with LTH can result in catch-up growth over 1 year of follow-up. The reproductive and psychological implications of these findings need to be confirmed in longer and larger prospective studies.

Physical exercise, nutrition and hormones: three pillars to fight sarcopenia.

BACKGROUND: Sarcopenia is a pathophysiological condition diffused in elderly people; it represents a social issue due to the longer life expectancy and the growing aging population. It affects negatively quality of life and it represents a risk factor for other pathologies, such as diabetes, cardiovascular disease, and obesity. No silver bullet exists to hinder sarcopenia, but it may be counteracted by physical exercise, nutrition, and a proper endocrine milieu. Indeed, we aim to analyze the scientific literature to give to clinician effective advices to counteract sarcopenia. Main text: Physical exercise, proper nutrition, optimized hormonal homeostasis represent the three pillars to fight sarcopenia. Physical exercise represents the most effective remedy to face sarcopenia, in particular if it is combined with a proper diet and with an adequate endocrine milieu. Consistency in training, adequate daily protein intake and eugonadism seems to be the keys to fight sarcopenia. The combination of these three pillars might act synergistically. CONCLUSIONS: Optimization of these factors may increase their efficiency; however, scientific data may be sometimes confusing so far. Therefore, we aim to give practical advices to clinician to identify and to highlight the most important aspects in each of these three factors that should be addressed.

Cytological Diagnoses Associated with Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features According to the Bethesda System for Reporting Thyroid Cytopathology: A Systematic Review and Meta-Analysis.

BACKGROUND: The recent introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) in the World Health Organization classification of thyroid tumors has significantly modified the risk of malignancy of cytological diagnoses. In fact, while this tumor was previously classified as a carcinoma (the encapsulated, noninvasive form follicular variant of papillary thyroid carcinoma), it is now considered a neoplasm with low malignant potential. Given that the cytological features of NIFTP are not specific and overlap with other pathologic entities, there is no specific cytological diagnostic category for NIFTP. To obtain more robust information about the cytological findings associated with NIFTP, published articles were systematically reviewed, and a meta-analysis of the data was conducted. METHODS: The review was conducted according to PRISMA guidelines. A comprehensive literature search of the PubMed/MEDLINE and Scopus databases was conducted using a combination of terms "noninvasive," "encapsulated," "follicular variant," "NIFTP," and "thyroid cancer." The search was updated to June 2018, and references of the retrieved articles were also screened. Only original articles reporting the classification of histologically proven NIFTPs with cytological findings according to The Bethesda System for Reporting Thyroid Cytopathology were eligible for inclusion. RESULTS: The literature search revealed 117 articles, of which 15 were included in the study. All studies were retrospective. A total of 915 NIFTP cases were retrieved. The incidence of cases cytologically classified according to the Bethesda system was as follows: non-diagnostic 3%, benign 10%, atypia of undetermined significance or follicular lesion of undetermined significance 30%, follicular neoplasm or suspicious for a follicular neoplasm 21%, suspicious for malignancy 24%, and malignant 8%. Mild heterogeneity between the studies was found. Publication bias was absent. CONCLUSIONS: This meta-analysis shows that the cytological diagnoses associated with NIFTP by fine-needle aspiration cytology includes a wide spectrum of findings. The majority of cases are cytologically indeterminate, and the remainder may be read as non-diagnostic, benign, or malignant. In order to develop an accurate presurgical diagnosis of these cases, further cytological and/or molecular characteristics need to be identified.

Effects of Ketone Bodies on Endurance Exercise.

Priorities for every athlete include improving endurance performance, optimizing training, nutrition, and recovery. Nutritional strategies are crucial to support athletes to perform at the highest level, and considering that muscular and hepatic glycogen stores are limited, alternative strategies to maximize fat metabolism have been suggested. A ketogenic diet has been proposed as a possible method of providing metabolic fuel during prolonged periods of exercise. However, clinical trials and empirical experience have produced contrasting results regarding the ergogenic value of a ketogenic diet. For this reason, using ketone esters and/or salts have been proposed to obtain nutritional ketosis without limiting carbohydrate intake. Exogenous ketones should not only represent an alternative metabolic fuel source, sparing carbohydrates, but they also may increase postexercise glycogen replenishment, decrease proteolysis, and act as metabolic modulators and signaling metabolites. While there are some encouraging results showing an increase in endurance performance, contrasting evidence regarding the efficacy of exogenous ketones for endurance performance is present and further studies should be performed to make a definitive statement.

Sport, doping and male fertility.

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being "fit" does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength - both excessive intensity and duration of exercise training - are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility.

Serum Homocysteine Levels in Men with and without Erectile Dysfunction: A Systematic Review and Meta-Analysis.

OBJECTIVES: Elevated levels of serum homocysteine (Hcy) have been associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). This meta-analysis was aimed to assess serum Hcy levels in subjects with ED compared to controls in order to clarify the role of Hcy in the pathogenesis of ED. METHODS: Medline, Embase, and the Cochrane Library were searched for publications investigating the possible association between ED and Hcy. Results were restricted by language, but no time restriction was applied. Standardized mean difference (SMD) was obtained by random effect models. RESULTS: A total of 9 studies were included in the analysis with a total of 1320 subjects (489 subjects with ED; 831 subjects without ED). Pooled estimate was in favor of increased Hcy in subjects with ED with a SMD of 1.00, 95% CI 0.65-1.35, p < 0.0001. Subgroup analysis based on prevalence of diabetes showed significantly higher SMD in subjects without diabetes (1.34 (95% CI 1.08-1.60)) compared to subjects with diabetes (0.68 (95% CI 0.39-0.97), p < 0.0025 versus subgroup w/o diabetes). CONCLUSIONS: Results from our meta-analysis suggest that increased levels of serum Hcy are more often observed in subjects with ED; however, increase in Hcy is less evident in diabetic compared to nondiabetic subjects. This study is registered with Prospero registration number CRD42018087558.

Cancer Rate of the Indeterminate Lesions at Low or High Risk According to Italian System for Reporting of Thyroid FNA.

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome. Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study. Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories. Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy.

Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma.

AIM: Due to the limits of calcitonin, other markers are warranted to better manage medullary thyroid carcinoma patients, and procalcitonin has been reported as promising. Here we aimed to evaluate procalcitonin as a marker of medullary thyroid carcinoma in the post-treatment follow-up. METHODS: Medullary thyroid carcinoma patients previously treated by thyroidectomy were enrolled. After complete imaging work-up (i.e. ultrasonography, computed tomography, magnetic resonance and 18FDG-PET-CT) we identified patients with structural recurrent/persistent medullary thyroid carcinoma (active medullary thyroid carcinoma) and subjects with no evidence of disease. Then, both calcitonin and procalcitonin were measured and their performance analyzed. RESULTS: The final series included 55 medullary thyroid carcinoma patients treated and followed-up for about five years. Of these, 43 were assessed as no evidence of disease, and 12 as active medullary thyroid carcinoma. The median value of procalcitonin was significantly higher ( P < 0.0001) in active medullary thyroid carcinoma patients (3.10 ng/mL) than in those with no evidence of disease (0.10 ng/mL). Also, calcitonin levels of active medullary thyroid carcinoma (96.7 pg/mL) were significantly ( P < 0.0001) higher than that of no evidence of disease (2.0 pg/mL). At the receiver operating characteristic curve analysis, the optimal cut-off of procalcitonin was ≥0.32 ng/mL with 92% sensitivity and 98% specificity, while the most accurate threshold of calcitonin was ≥12.0 pg/mL with 100% sensitivity and 91% specificity. There was no active medullary thyroid carcinoma with simultaneously negative results of procalcitonin and calcitonin. CONCLUSIONS: Procalcitonin is reliable in discriminating medullary thyroid carcinoma patients with active disease from those with no evidence of disease. We suggest using procalcitonin as complementary to calcitonin to follow-up medullary thyroid carcinoma patients.

Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry.

BACKGROUND: The total testosterone (T) cutoffs clinically adopted to define late-onset hypogonadism (LOH) do not consider the differences that exist between different analytical platforms, nor do they consider the body mass index (BMI) or age of the patient. We aimed at providing method, age and BMI-specific normal values for total T in European healthy men. METHODS: A total of 351 eugonadal healthy men were recruited, and total T was measured with four automated immunometric assays (IMAs): ARCHITECT i1000SR (Abbott), UniCel DxI800 (Beckman Coulter), Cobas e601 (Roche), IMMULITE 2000 (Siemens) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference ranges (RRs) were calculated for each method. RESULTS: Passing and Bablok regression analysis and Bland-Altman plot showed an acceptable agreement between Abbott and LC-MS/MS, but a poor one between LC-MS/MS and the other IMAs. Age-specific T concentrations in non-obese (BMI <29.9 kg/m2) men were greater than in all men. The total T normal range, in non-obese men aged 18-39 years, measured with LC-MS/MS was 9.038-41.310 nmol/L. RRs calculated with LC-MS/MS statistically differed from the ones calculated with all individual IMAs, except Abbott and among all IMAs. Statistically significant differences for both upper and lower reference limits between our RRs and the ones provided by the manufacturers were also noticed. CONCLUSIONS: We calculated normal ranges in a non-obese cohort of European men, aged 18-39 years, with four commercially available IMAs and LC-MS/MS and found statistically significant differences according to the analytical method used. Method-specific reference values can increase the accuracy of LOH diagnosis and should be standardly used.