Normalization of Spexin Levels in Patients with Obesity Submitted to Bariatric Surgery.

PURPOSE: Spexin is expressed by white fat tissue and other endocrine organs. A negative correlation between spexin and gluco-lipidic metabolism, energy homeostasis, and food intake has been reported. The objectives of this study are (1) to compare spexin levels between patients with obesity (study group) and normal-weight subjects (control group); (2) to evaluate spexin levels after bariatric surgery; and (3) to identify a correlation between spexin and weight loss/metabolic profile of patients with obesity. MATERIALS AND METHODS: We examined 53 patients with obesity (mean BMI 48.5 ± 9.4 kg/m2) who underwent bariatric surgery, compared to 55 normal-weight subjects. Serum spexin levels were assessed at baseline (study and control group) and at 3 and 6 months after surgery in patients with obesity. RESULTS: Spexin at baseline was significantly lower in the study group (p < 0.0001). At 3 and 6 months after bariatric surgery, spexin significantly increased compared to pre-surgical levels (p < 0.001) reaching control group levels (p = 0.08) at 6 months. In patients with obesity, pre-surgical spexin was similar in patients with and without comorbidities. No correlation between spexin and C-reactive protein (p = 0.8) and HOMA index (p = 0.5) was found. A significant negative correlation between age and pre-surgical spexin was observed (p = 0.03). At multivariable analysis, no correlation between Δ spexin and pre-surgery BMI, HOMA index, age, and 6-month TWL% was found. CONCLUSION: This study demonstrates that patients with obesity have significantly lower spexin levels than healthy subjects. After surgery, spexin levels of the study group become similar to those observed in the normal-weight group.

Effect of Pre-Existent Sarcopenia on Oncological Outcome of Advanced Thyroid Cancer Patients Treated with Tyrosine Kinase Inhibitors.

(1) Background: Sarcopenia is associated with poor survival and treatment outcomes in several human cancers. The aim of the study was to investigate the prevalence of sarcopenia in a cohort of 58 Caucasian patients with advanced thyroid cancer before and during TKI treatment. The impact of this condition on the outcome of patients was also evaluated. (2) Methods: Sarcopenia was evaluated using the Skeletal Muscle Index (SMI). (3) Results: Pre-treatment sarcopenia was found in 20.7% of patients and this condition significantly affected treatment outcome, emerging as the parameter that has the greatest impact on Progression Free Survival (PFS) (HR 4.29; 95% CI, 1.21−15.11, p = 0.02). A significant reduction in SMI values was observed 3 (p = 0.002) and 12 months (p < 0.0001) after TKI treatment. At a 12-month follow-up, sarcopenia prevalence increased up to 38.5%. Here, 12-month sarcopenia was predicted by a lower SMI (p = 0.029), BMI (p = 0.02) and weight (p = 0.04) and by the presence of bone metastases (p = 0.02). (4) Conclusions: This is the first study that evaluated sarcopenia prevalence and its change over time in Caucasian patients with advanced thyroid cancer under TKI therapy. Sarcopenia seems to be a prognostic factor of TKI treatment outcome, suggesting the importance of the assessment of the nutritional status and body composition in advanced thyroid cancer patients.

Follow-up after bariatric surgery: is it time to tailor it? Analysis of early predictive factors of 3-year weight loss predictors of unsuccess in bariatric patients.

Bariatric surgery (BS) is the most effective treatment strategy for obesity. Nevertheless, a subset of patients does not reach a successful weight loss or experience long-term weight regain. Conflicting evidence exists regarding predictors of BS outcomes. We aimed to define the early factors linked to 3 year unsuccessful weight loss in order to promote a tailored close follow-up. We enrolled 443 patients who underwent BS from January 2014 to December 2018 with a 3 year follow-up. An unsuccessful BS outcome was defined as a percentage of total weight loss (%TWL) < 20. We compared the characteristics between successful and unsuccessful patients in order to identify predictor factors of unsuccess after surgery. We found that the proportion of patients with unsuccessful weight loss progressively increased from one to three years after BS. In a multiple regression model, only 1 month %TWL and sleeve gastrectomy (SG) were significantly associated with 3 year unsuccessful weight loss. We stratified our cohort in four groups according to the risk of BS unsuccess, in terms of 1 month %TWL and type of surgery (SG vs gastric bypass). Interestingly, groups showed a significant difference in terms of %TWL at each follow-up point. Patients submitted to SG with lower 1 month %TWL must be considered at higher risk of future weight regain; consequently, they require a tailored and closer follow-up.

Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.

A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI.

(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score <3 than in those with CONUT score ≥3 (p < 0.0001). CONUT score was the only independent prognostic factor associated with PFS (p = 0.021) and OS (p = 0.007). (4) Conclusions: CONUT score represents a relatively new screening tool, easily applicable in clinical practice and potentially useful in predicting prognosis in thyroid cancer patients treated with TKIs.

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

INTRODUCTION: Association between hypercalcitoninemia and pathological conditions such as autoimmune thyroiditis (AIT) or differentiated thyroid carcinoma (DTC) has been addressed, with conflicting results. We evaluated the prevalence and the clinical relevance of elevated basal serum calcitonin (CT) levels in non-neoplastic (nodular goiter [NG] and AIT) and neoplastic thyroid diseases (DTC). METHODS: We retrospectively evaluated 3,250 consecutive patients with thyroid nodular disease who underwent fine-needle aspiration cytology with adequate sample. After exclusion of medullary thyroid cancer (MTC) patients were divided according to the presence/absence of thyroid autoimmunity into NG or nodular autoimmune thyroiditis (N-AIT) and, according to cytological results, in benign or suspicious/malignant nodules. RESULTS: One hundred ninety-seven/3,250 patients (6.0%) showed CT level >10 pg/mL. In 11/3,250 (0.3%) cases, a final histological diagnosis of MTC was made, while the remaining 186/3,250 patients (5.7%) had non-MTC-related hypercalcitoninemia (CT > 10 pg/mL). According to cytological diagnosis, the rate of hypercalcitoninemia was similar in class II and class V-VI groups (5.4 vs. 6.9%, p = 0.4). The occurrence of hypercalcitoninemia was significantly higher in patients with NG (166/2,634 [6.3%]) than in patients with N-AIT (20/605 [3.3%]) (p = 0.004). However, after matching by sex, no difference was found between the 2 groups (NG and N-AIT). These results were confirmed in 598 patients submitted to surgery. CONCLUSIONS: AIT and DTC seem not to affect serum CT levels in patients with thyroid nodules. Therefore, hypercalcitoninemia, in these patients, should be submitted to the same diagnostic workup than patients without AIT or DTC.

The impact of CPT1B rs470117, LEPR rs1137101 and BDNF rs6265 polymorphisms on the risk of developing obesity in an Italian population.

OBJECTIVE: This study aimed to analyze 11 single nucleotide polymorphisms (SNPs) belonging to 9 genes involved in metabolic pathways (BDNF rs6265; PNPLA3 rs2294918 and rs2076212; CIDEA rs11545881; NTRK2 rs2289658; ALOX12 rs1126667; ALOX12B rs2304908; LEPR rs1137101; CPT1B rs470117 and rs8142477; rs2305507 CPT1A) in obese patients and controls. METHODS: Polymorphisms were analyzed in 300 severe obese patients undergoing bariatric surgery (body mass index >30 kg/m2) and 404 control subjects in order to evaluate their association with obesity and clinical variables. RESULTS: Our findings showed significant differences for the allelic distributions of CPT1B rs470117 and LEPR rs11371010 in obese subjects compared to controls. The BDNF rs6265 correlates with obesity only when associated with the other two SNPs. In particular, for CPT1B rs470117 and LEPR rs1137101, the rare allele was associated with a reduced risk of developing the obese phenotype, whereas the simultaneous presence of the common C allele for rs470117 and A allele for rs1137101 was more frequent in obese patients (p = 0.002, OR = 1.417). A significant association between CPT1B rs470117 and steatosis was found. Moreover, we observed that by associating the rare allele T of the BDNF rs6265 with the most common alleles of the SNPs CPT1B rs470117 and LEPR rs1137101, the combination of T-C-A alleles was associated with a higher risk of developing an obese phenotype (p = 0.001, OR = 1.6679). CONCLUSIONS: Our results suggest that SNPs CPT1B rs470117 and LEPR rs1137101 taken individually and in association with BDNF rs6265 may be involved in an increased risk of developing obese phenotype in an Italian cohort.

Controlling Nutritional Status (CONUT) Score and Micronutrient Deficiency in Bariatric Patients: Midterm Outcomes of Roux-en-Y Gastric Bypass Versus One Anastomosis Gastric Bypass/Mini Gastric Bypass.

BACKGROUND: Two of the most common bariatric procedures performed worldwide are Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB). Comparative data regarding nutritional status are lacking and no previous study focus on malnutrition according to a validated score. METHODS: Retrospective data from a single institution were reviewed. Anthropometric variables and nutritional data were assessed. The primary aim was to analyze and compare the nutritional status before and 3 years after RYGB vs OAGB using the controlling nutritional status (CONUT) score. The incidence of micronutrient deficiency and the remission of comorbidities in each group were defined as secondary outcomes. RESULTS: Fifty-seven patients in each arm were enrolled. A 3-year mild malnutrition (CONUT score 2-3) was found in 38% and 37.05% in the RYGB and OAGB groups, respectively (p > 0.05). In terms of percentage of total weight loss (%TWL) and percentage of adjustable weight loss (%AWL), no differences were found between OAGB and RYGB groups. OAGB and RYGB patients had similar vitamin deficiencies. Anemia, hypoproteinemia, hypoalbuminemia, and hypocalcemia were comparable between groups. At 3-year follow-up, total protein and albumin values were similar between arms while prealbumin deficit was more frequent after OAGB than after RYGB. The rate of type 2 diabetes (87.5% in OAGB and 92% in RYGB), arterial hypertension (51.6% in OAGB and 58.3% in RYGB), and dyslipidemia (69.7% in OAGB and 78.6% in RYGB) remission was not significantly different between the two groups. CONCLUSIONS: Postoperative CONUT score, micronutrient deficiency, comorbidity remission, and improvement of anthropometric parameters 3 years postoperatively were comparable between RYGB and OAGB groups.

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

Introduction: The management of patients with indeterminate thyroid nodules, which account for 10-25% of thyroid fine needle aspiration biopsies (FNABs), is still very challenging. Aim: To verify the utility of the seven-gene panel in combination with ultrasound features in the clinical management of indeterminate thyroid nodules. Results: The study group included 188 indeterminate thyroid nodules, divided into TIR3A (56.4%) and TIR3B (43.6%). A significant correlation between US categories and both cytological and molecular results was observed. In detail, TIR3B cytology was more frequent in EU-TIRADS 4 and 5 nodules (54.7 and 50%, respectively) than in EU-TIRADS 2 and 3 nodules (31%, p = 0.04). Similarly, the rate of a nodule with a mutation increased with the increase of US risk class (6.0% in EU-TIRADS 2 and 3, 9.3% in EUTIRADS-4 and 27.8% in EUTIRAD-5, p = 0.01). Among thyroid nodules submitted to surgery, final histology was benign in 61.4% nodules, while malignancy was diagnosed in 38.6% nodules. Using US score as tool for decision-making in TIR3A subgroup, we correctly classified 64.5% of thyroid nodules. The second tool (seven-gene panel test) was used in the subgroup of US high-risk nodules. By multiple tests with a series approach (US in all cases and US plus seven-gene panel in US high risk nodules) 84% of cases were correctly classified. In TIR3B nodules, using only seven-gene panel as tool for decision making, we correctly classified 61.9% of indeterminate nodules. By multiple tests with series approach (seven-gene panel in all cases and seven-gene panel plus US score in non-mutated nodules) only a slight improvement of thyroid nodule classification (66.6%) was observed. Conclusions: US score seems able to correctly discriminate between TIR3A nodules in which a conservative approach may be used, and those in which additional test, such as molecular test, may be indicated. On the contrary, in TIR3B nodules both US risk stratification and seven-gene panel seem to be of little use, because the risk of thyroid cancer remains high regardless of US score and mutational status.

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

Background: The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be performed. In addition, this system is used to plan the long-term follow-up of patients with cytological benign thyroid nodules. The aim of our study was to evaluate the ATA US risk-adapted approach for repeating cytology in a large retrospective cohort of consecutive benign nodules with a second FNAC repeated after a median follow-up of 3.8 years (range 1.0-14.2 years). Methods: We retrospectively evaluated 1010 thyroid nodules, with an initial benign cytological diagnosis, that underwent at least one repeat FNAC during the follow-up. Results: The rate of missed cancer in the whole cohort of thyroid nodules was 1.0%, and it increased along by the US risk class (0.8% in very low/low-risk, 1.2% in intermediate-risk, and 3.1% in high-risk nodules). The 2015 ATA US risk stratification system showed a very high accuracy in selecting nodules that did not require a second FNAC (negative predictive value = 99.1%). In addition, the rate of missed cancer significantly increased along with the increase in the US risk class in nodules that showed an enlarged volume (0.4% in the low-risk class and 6.4% in the high-risk class, p = 0.005), while it was very low and not associated with the US features in the subgroup of thyroid nodules that did not grow during the follow-up (p = 0.96). Conclusions: Our results confirm the accuracy of the ATA recommendations in selecting benign nodules for FNAC repetition during the follow-up. An additional cytological evaluation maybe avoided in benign thyroid nodules with low-risk US features, regardless of the evidence of growth during the follow-up. While the utility of the routine repeat FNAC in all benign nodules with high-risk US features remains to be defined, based on our results, repetition of FNAC seems to be indicated in nodules with evidence of growth during the follow-up.

Novel Pathogenic Variants of the AIRE Gene in Two Autoimmune Polyendocrine Syndrome Type I Cases with Atypical Presentation: Role of the NGS in Diagnostic Pathway and Review of the Literature.

Background. Autoimmune polyglandular syndrome type 1 (APS-1) with or without reversible metaphyseal dysplasia is a rare genetic disorder due to inactivating variants of the autoimmune regulator, AIRE, gene. Clinical variability of APS-1 relates to pleiotropy, and the general dysfunction of self-tolerance to organ-specific antigens and autoimmune reactions towards peripheral tissues caused by the underlying molecular defect. Thus, early recognition of the syndrome is often delayed, mostly in cases with atypical presentation, and the molecular confirm through the genetic analysis of the AIRE gene might be of great benefit. Methods. Our methods were to investigate, with a multigene panel next generation sequencing approach, two clinical cases, both presenting with idiopathic hypoparathyroidism, also comprising the AIRE gene; as well as to comment our findings as part of a more extensive review of literature data. Results. In the first clinical case, two compound heterozygote pathogenic variants of the AIRE gene were identified, thus indicating an autosomal recessive inheritance of the disease. In the second case, only one AIRE gene variant was found and an atypical dominant negative form of APS-1 suggested, later confirmed by further medical ascertainments. Conclusions. APS-1 might present with variable and sometimes monosymptomatic presentations and, if not recognized, might associate with severe complications. In this context, next generation diagnostics focused on a set of genes causative of partially overlapping disorders may allow early diagnosis.

Cardiovascular Benefits and Lipid Profile Changes 5 Years After Bariatric Surgery: A Comparative Study Between Sleeve Gastrectomy and Roux-en-Y Gastric Bypass.

INTRODUCTION: Visceral adipose tissue has been linked with cardiovascular events. Visceral adiposity index (VAI) is a routinely applicable tool for evaluation of visceral adipose dysfunction and linked to 10 year-cardiovascular risk. No previous studies have evaluated the changes over time of the VAI in patients who underwent different types of bariatric surgery. MATERIALS AND METHODS: We reviewed data of 42 patients who underwent laparoscopic sleeve gastrectomy (LSG) and 61 patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). VAI, lipid profile, and several anthropometric variables were measured before and after 5 years following surgery. RESULTS: During the studied time period, the BMI was similar between LSG and LRYGB patients (34.1 vs 31.6; p = 0.191), but the percentage of total weight loss (%TWL) for LRYGB was significantly higher than LSG (31.3% vs 23.0%; p < 0.001). LRYGB patients had a significant improvement of all lipid parameters evaluated over time, while LSG patients experienced only a reduction in triglycerides (TG) levels and an increase in HDL cholesterol (HDL-C). VAI values were similar in the two groups at baseline as well at the last follow-up point (5-year VAI, LSG: 0.93, RYGB: 0.93; p = 0.951). At multivariate regression analysis, 5-year-%TWL was the only independent predictor of a greater amount of VAI reduction over time. CONCLUSION: Bariatric surgery, independent of the type of surgical procedure, decreases the cardiovascular disease (CVD) risks due to weight loss and improvement of lipid parameters. VAI could be a useful tool to better identify eligible patients for bariatric surgery and to determine the success of surgery.

ONE MONTH WEIGHT LOSS PREDICTS THE EFFICACY OF LIRAGLUTIDE IN OBESE PATIENTS: DATA FROM A SINGLE CENTER.

Objective: Liraglutide is a glucagon-like peptide 1 receptor agonist which acts through peripheral and central receptor pathways affecting food intake. Preliminary identification of responder patients represents a crucial point to reduce an inappropriate exposure to the drug and the health expenditure. The primary endpoint of our study was to identify predictors of liraglutide efficacy in the short term follow-up. The secondary endpoint was to evaluate the treatment efficacy stratified by the underlying psychiatric disorder. Methods: We evaluated a cohort of 100 patients (77 females, 23 males, mean body mass index 38.6 ± 3.2 kg/m2) who were evaluated at baseline, and after 1, 3, and 6 months of treatment. Liraglutide efficacy was defined by a weight loss ≥5% of initial weight. Sociodemographic/metabolic parameters, food intake, smoking habit, and physical activity were correlated with liraglutide efficacy. Results: There was a significant weight loss after 1 month of therapy, as well as after 3 and 6 months when compared to the baseline (P<.0001; 27%, 45%, and 57% of patients showed a weight loss ≥5%, respectively). No difference was found in weight loss between the 3 groups of patients (with binge eating, with/without psychiatric disorders). The weight loss at 1 month was the only predictor of a positive response to the treatment. Conclusion: Our results confirm the efficacy of liraglutide even at a lower dose than conventional. The early response to the drug seems to be a good predictor of long-term efficacy and it might be useful in clinical practice to identify patients in whom liraglutide may induce a significant weight loss. Abbreviations: BMI = body mass index; EMA = European Medicine Agency; FDA = Food and Drug Administration; GLP-1 RA = glucagon-like peptide 1 receptor agonist.

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

Context: Recently, the American Thyroid Association (ATA) and the European Thyroid Association (ETA) have proposed that thyroid ultrasound (US) should be used to stratify the risk of malignancy in thyroid nodules and to aid decision-making about whether fine-needle aspiration cytology (FNAC) is indicated. Objective: To validate and to compare the ATA and ETA US risk stratification systems of thyroid nodules in a prospective series of thyroid nodules submitted to FNAC. Setting: We prospectively evaluated 432 thyroid nodules selected for FNAC from 340 patients. Cytology reports were based on the five categories according to the criteria of the British Thyroid Association. Results: The proportion of Thy2 nodules decreased significantly, whereas the proportion of Thy4/Thy5 nodules significantly increased with increasing US risk class (P < 0.0001). The ability to identify benign and malignant nodules was similar between ATA and ETA systems. According to ATA and ETA US risk stratification systems, 23.7% and 56.0% nodules did not meet the criteria for FNAC, respectively. Considering only categories at lower risk of malignancy, the cumulative malignancy rate in these nodules was 1.2% for ATA and 1.7% for ETA US risk stratification systems. Conclusions: ETA and ATA US risk stratification systems provide effective malignancy risk stratification for thyroid nodules. In clinical practice, using this approach, we should be able to reduce the number of unnecessary FNAC without losing clinically relevant thyroid cancer.

Bariatric Surgery Reduces Serum Anti-mullerian Hormone Levels in Obese Women With and Without Polycystic Ovarian Syndrome.

PURPOSE: Obesity in fertile women has negative effect on fertility. Anti-mullerian hormone (AMH) represents a good index of fertility, and it is considered a marker of ovarian reserve and of polycystic ovarian syndrome (PCOS) gravity. Previous studies evaluated the relationship between obesity and AMH with contradictory results. The aim of the study was to investigate the relationship between obesity and AMH and the changes of AMH in obese women in reproductive age submitted to bariatric surgery. MATERIALS AND METHODS: Fifty-five obese patients between 18 and 39 years with (29 patients) and without PCOS (26 patients) were compared with a control group of normal weight women with (24 patients) and without PCOS (19 patients). Fourteen obese women with PCOS and 18 without PCOS underwent to bariatric surgery. Serum AMH, testosterone, androstenedione, and DHEAS were performed in all patients before and 1 year after surgical intervention. RESULTS: AMH was significantly higher in the PCOS groups (p < 0.001), both in obese (5.84 ± 3.94 ng/ml) and non-obese women (7.35 ± 4.39 ng/ml). AMH was positively related to testosterone (p < 0.0001), androstenedione (p = 0.0005), and DHEAS (p = 0.003). After bariatric surgery, AMH levels were reduced in the both PCOS (p = 0.02) and non-PCOS group (p = 0.04). CONCLUSIONS: AMH levels are elevated in PCOS patients regardless of the body weight. Bariatric surgery is effective in the normalization of AMH levels (a possible indirect marker of better fertility) only in obese patients with PCOS.

Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab.

OBJECTIVE: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab. DESIGN AND METHODS: We report nine cases of ipilimumab-induced hypophysitis in a cohort of 273 patients treated with ipilimumab between 2006 and 2015, as part of clinical trials or after its marketing. Thyroid function tests were scheduled at screening and during follow up (every 21 days) in all patients. Cortisol, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1 were measured only in case of clinical suspicion. RESULTS: The incidence of hypophysitis was 3.3%. The most frequent pituitary failure was adrenocorticotropic hormone and thyroid stimulating hormone secretion with a complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic hormone during follow up. All patients had negative pituitary antibodies. The main symptoms at diagnosis were fatigue and headache. CONCLUSION: Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy. Pituitary magnetic resonance imaging does not seem pivotal for a definite diagnosis if not performed at the onset of disease.

Obesity Does Not Modify the Risk of Differentiated Thyroid Cancer in a Cytological Series of Thyroid Nodules.

BACKGROUND: A possible impact of obesity on the risk of thyroid cancer has been postulated in some studies, but it remains controversial. OBJECTIVE: To investigate the association between obesity and differentiated thyroid carcinoma in a population of unselected patients subjected to fine-needle aspiration cytology (FNAC) for thyroid nodules. METHODS: We retrospectively evaluated the results of FNAC of thyroid nodules in 4,849 patients (3,809 females and 1,040 males; mean age 55.9 ± 14.1 years). Patients were stratified according to their body mass index (BMI). There were 1,876 (38.7%) normal-weight patients (BMI 18-24.9), 1,758 (36.2%) overweight (BMI 25-29.9), 662 (13.7%) grade 1 obese (BMI 30-34.9), 310 (6.4%) grade 2 obese (BMI 35-39.9) and 243 (5.0%) grade 3 obese (BMI >40). RESULTS: The prevalence of suspicious or malignant nodules (Thy4/Thy5) did not differ across the 5 BMI groups, i.e. it was 6.8% in normal-weight patients, 6.3% in overweight patients, 6.3% in grade 1 obese patients, 4.0% in grade 2 obese patients and 4.2% in grade 3 obese patients (p = 0.29). The prevalence of Thy4/Thy5 nodules did not differ when males and females were evaluated separately (p = 0.22 and p = 0.12, respectively). A significant, lower rate of Thy4/5 cytology was observed in female patients with grade 2-3 obesity (odds ratio 0.51; 95% confidence interval 0.284-0.920; p = 0.009). CONCLUSIONS: The results of this study, in a retrospective series of patients with thyroid nodules, do not confirm previous findings reporting an association between obesity and differentiated thyroid carcinoma. Thus, obese patients with nodular thyroid disease should be managed the same as normal-weight patients.

Is sleeve gastrectomy a therapeutic procedure for all obese patients?

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a worldwide surgical procedure for morbid obesity. However patients selection is still anecdotal. The aim of this study is to analyse clinical and anthropometric parameters correlated with LSG and to check the validity of this procedure for different categories of obese patients. METHODS: Two-hundred one consecutive patients were submitted to LSG as a primary bariatric procedure between 2008 and 2014. One year follow-up was completed in 159 patients. Smaller groups of patients completed 2 and 3 years follow-up (78, 46 patients respectively). Median preoperative body mass index (BMI) was 45.4 kg/m2 (range: 34.8-73.8); 135 patients (80%) had one or more comorbidities. Potential correlations between age, gender, preoperative BMI, preoperative excess weight, early excess weight loss (EWL) and 1 and 3 year-EWL were investigated. RESULTS: All procedures were regularly completed with laparoscopic approach without conversion to laparotomy. Postoperative complications occurred in six patients (3.7%); no postoperative mortality was observed. Median one-year BMI and EWL were 32.8 kg/m2 and 55.34%, respectively. Three year-EWL was significantly influenced by age, and early EWL. A complete normalization of glycemic levels after the three-year follow-up was also observed in high percentage of diabetic patients. In patients with preoperative BMI>50 kg/m2 we observed most failure cases in terms of EWL and the worst metabolic results. CONCLUSIONS: Our experience indicates that LSG is a safe procedure with satisfactory three-year late weight loss in patients with preoperative BMI <50 kg/m2. Promising results, in terms of improvements of comorbidities, were also observed. These results make LSG one of the most attractive first stage surgical procedure for morbid obesity.

Weight loss associated with bariatric surgery does not restore short telomere length of severe obese patients after 1 year.

BACKGROUND: Telomere shortening is physiologically associated with ageing but it may be influenced by oxidative stress and chronic inflammation, linked to obesity. Thus, obesity might represent an additional cause of telomere attrition. We aim to study relative telomere length (RTL) in obese subjects with and without metabolic syndrome and to assess the effect of weight loss induced by bariatric surgery. METHODS: We evaluated RTL in 107 obese subjects (62 with metabolic syndrome and 45 without metabolic syndrome), compared to 130 age-matched non-obese subjects. We also measured RTL in a subgroup of 93 obese patients prior to and 3, 6, 9 and 12 months after surgery. RESULTS: RTL of obese subjects was significantly shorter (p<0.0001) than non-obese subjects but without differences between patients with and without metabolic syndrome (p=0.19). RTL was significantly shorter than baseline at 3, 6, 9 and 12 months after bariatric surgery. CONCLUSIONS: These results confirm that obese subjects have shorter telomeres compared to non-obese subjects, but RTL is not influenced by the presence of metabolic syndrome. RTL shows an additional attrition during the immediate post-operative period, probably due to a catabolic state.

Effects of Acute Recombinant Human TSH on Serum Ghrelin Levels.

UNLABELLED: Recent findings showed the presence of a reciprocal relationship between thyroid hormones and ghrelin, although the exact mechanism is not known. DESIGN: Our study is addressed to evaluate the effect of acute exogenous rhTSH administration on serum ghrelin levels in athyreotic patients on replacement l-thyroxine therapy. The study group included 50 patients (16 males and 34 females) submitted to total thyroidectomy and 131-iodine remnant ablation for differentiated thyroid cancer on l-thyroxine therapy. Mean age was 47.5 ± 16.5 years and mean BMI was 25.6 ± 5.01 kg/m(2). rhTSH was administrated at the dosage of 0.9 mg i.m. once daily for two consecutive days. Blood samples were taken between 08.00 and 09.00 after a overnight fasting for measurement of TSH, FT3, FT4, and ghrelin before the first administration of rhTSH and for measurement of TSH and ghrelin 24, 48, 72, and 96 h after the first administration of rhTSH. RESULTS: Mean ± SD values of basal TSH were 0.54 ± 0.77 µU/ml without significant difference between females and males. As expected, after rhTSH administration TSH concentrations increased at 24 and 48 h with peak TSH values ranging from 20.20 to 313 µU/ml (mean ± SD 98.4 ± 66.7 µU/ml). Mean ± SD values of basal ghrelin were 1085 ± 373 pg/ml without significant difference between males and females. After rhTSH administration ghrelin concentrations decreased significantly (p < 0.01) at 24 h (mean ± SD 934 ± 314 pg/ml p < 0.01) and returned to pre-treatment levels at 96 h. CONCLUSION: Our study demonstrates that acute exogenous TSH administration has a suppressive effect on ghrelin secretion independent from changes in thyroid status.