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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) Graphical abstract

(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

Objective Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. Design and methods We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer–BioNTech and Moderna). Results Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. Conclusions COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.

(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.

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. 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. 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. Postoperative CONUT score, micronutrient deficiency, comorbidity remission, and improvement of anthropometric parameters 3 years postoperatively were comparable between RYGB and OAGB groups.

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.

IntroductionThe management of patients with indeterminate thyroid nodules, which account for 10–25% of thyroid fine needle aspiration biopsies (FNABs), is still very challenging.AimTo verify the utility of the seven-gene panel in combination with ultrasound features in the clinical management of indeterminate thyroid nodules.ResultsThe 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.ConclusionsUS 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.

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 perf...

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.

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. 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. 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. 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.

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

Objective: Myotonic dystrophy (DM) is a monogenic disorder. It is caused by expansion of a cytosine-thymineguanine triplet in the DMPK gene which encodes for myotonic dystrophy protein kinase (DMPK).Methods: A 24-year-old man with DM and the DMPK mutation presented with elevated adrenocorticotropic hormone (ACTH) levels twice (152 and 185 pg/mL; normal value is 10 to 52 pg/mL) with normal cortisol levels (134.6 and 113.0 ng/mL, or 371.3 and 311.7 nmol/L; normal values are 67 to 226 ng/mL or 184.8 to 623.5 nmol/L). ACTH, corticotropin-releasing hormone (CRH) and insulin tolerance test (ITT) demonstrated normal cortisol response to ACTH and partial response to CRH and ITT tests, and ACTH hyperresponse to CRH and ITT. We suspected ACTH and/or ACTH receptor (ACTHR) mutations and evaluated the genetic profile for pro-opiomelanocortin (POMC), melanocortin 2 receptor (MC2R) and follicle-stimulating hormone receptor (FSHR) genes.Results: No mutations were found in either the MC2R or FSHR genes. The patient was heterozygous for the c.614A>G mutation corresponding to a p.53D>G substitution with a glycine instead of an aspartate in position 53 in POMC gene. This mutation was outside the sequence for ACTH (which spans amino acids 138 to 176) but was included in the part originating the N-terminal peptide of pro-opiomelanocortin (also called pro-γ-melanocyte stimulating hormone) which spans amino acids 27 to 102 and is involved in the regulation of adrenal steroidogenesis.Conclusion: The pathologic expansion of the cytosine-thymine-guanine triplet repeat in the 3' noncoding region of DMPK could explain the hyperresponse of ACTH typical of DM. The mutation of pro-γ-melanocyte-stimulating hormone could be associated with the abnormal response of cortisol, compatible with a partial adrenal insufficiency. Other studies are necessary to demonstrate this hypothesis.Abbreviations: ACTH = adrenocorticotropic hormone CRH = corticotropin-releasing hormone DM = myotonic dystrophy DMPK = myotonic dystrophy protein kinase FSHR = follicle-stimulating hormone receptor ITT = insulin tolerance test MC2R = melanocortin 2 receptor MSH = melanocyte-stimulating hormone POMC = pro-opiomelanocortin

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.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.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 BMI50 kg/m2 we observed most failure cases in terms of EWL and the worst metabolic results.Our experience indicates that LSG is a safe procedure with satisfactory three-year late weight loss in patients with preoperative BMI50 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.

An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared. We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3 years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC. FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a “CHAID tree-building algorithm”, familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01). Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

Background Liraglutide is a once-daily injectable medication approved for the treatment of obesity. Hereby we report the feasibly, adherence and efficacy of liraglutide treatment in a sample of individuals with mood disorders and obesity. Methods and Sample Twenty-nine patients with Bipolar or Major Depressive Disorder received liraglutide once daily subcutaneously at a dose gradually titrated from 0.6 mg to 3 mg. All patients were obese and had previously failed multiple healthy lifestyle interventions, including exercise and diet programs. Patients’ weight was recorded before liraglutide treatment (T0) and then 1 (T1), 3 (T3), and 6 months (T6) following T0. Results Mean baseline (T0) weight was 110.54 Kg (± 24.95). Compared to baseline, the percentage of weight loss was 3.37 % at T1, 7.85% at T3 and 10.20% at T6. Thirty-one percent (n = 9) of patients had no side effects, 34.48% (n = 10) had one, 24.14% (n = 7) had two, and 10.34% (n=3) had three side effects. All 29 subjects were still on liraglutide at T1; 79.31% and 48.28% were on liraglutide at T3 and T6. No significant relationship was found between liraglutide dose and likelihood to continue the medication. No patient showed a worsening of the psychiatric condition due to liraglutide treatment. Acceptability and satisfaction with treatment were good for the 48% that completed the study. Conclusions Liraglutide treatment was efficacious, accepted and tolerated by approximately 50% of our sample, followed up for a period of 180 days. Larger, longer, controlled, prospective studies are warranted.

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.

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. 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. AMH was significantly higher in the PCOS groups (p

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. 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. RTL of obese subjects was significantly shorter (p

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. 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. 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. 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 is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m2, early onset and a family history of being overweight. Candidate genes were screened by direct sequence analysis to search for rare genetic variations. The common LEP -2548 G/A polymorphism was also evaluated for its influence on the BMI (in obesity patients) and for obesity risk, using a case-control study involving 117 healthy individuals. Two different non-synonymous alterations in MC4R were found in two patients: the p.(Thr112Met), previously described in the literature as a probable gene involved in the obesity phenotype, and the novel p.(Tyr302Asp) variant, predicted to be pathogenic by in silico evaluations and family segregation studies. The LEP -2548 G/A polymorphism was not associated with the BMI or obesity risk. In conclusion, we have reported a novel mutation in MC4R in a family of Italian patients with severe obesity. Screening for MC4R could be important for directing the carriers of mutations towards therapy including partial agonists of the MC4R that could normalize their appetite and inhibit compulsive eating. Next-generation sequencing could be used to clarify the genetic basis of obesity in the future.

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.

We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was measured before and after therapy every 3-6 months up to 3 yr. Three years after therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3% hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%. Definitive hypothyroidism was significantly higher in GD (p

We investigated whether serum thyroglobulin determination before surgery for differentiated thyroid carcinoma may have any prognostic value with regard to tumour extension and disease outcome in a retrospective series of 71 patients with papillary thyroid cancer. Presurgical serum thyroglobulin levels were correlated with the size of the primary tumoral nodule (p = 0.006) and of the whole thyroid (p = 0.02). The same correlation was found in a control group of patients with benign thyroid nodules, confirming that presurgical serum thyroglobulin cannot be used for the differential diagnosis of thyroid carcinoma. Presurgical serum thyroglobulin levels did not differ among patients with tumor limited to thyroid gland or extending to cervical lymph nodes or invading outside the thyroid capsule or metastasising to distant size. In addition presurgical serum thyroglobulin levels were not correlated with the disease outcome after a mean follow-up of 9 years: no difference was found among patients in complete remission or with persistent disease or dead from thyroid cancer. In conclusion, this study failed to show any prognostic value of presurgical serum thyroglobulin determination that consequently should not be measured.

Management of thyroid nodules is one of the most controversial issues in thyroidology. Different approaches derive from geographical variation in presentation, inadequate or incomplete clinical diagnosis, lack of prospective controlled studies and, frequently, the different cultural backgrounds of physicians. This review aims to offer a practical approach to the management of nodular thyroid disorders, considering the way in which the pathophysiology of the disease provides clues to the correct clinical diagnosis and therapy.

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 fifty 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/m². 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 h, 48 h, 72 h 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 h and 48 h with peak TSH values ranging from 20.20 to 313 µU/ml (mean ± SD 98.4±66.7µU/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

Autoimmune thyroiditis (AIT) may be associated with other organ-specific autoimmune disorders, including autoimmune gastritis, but the prevalence of this association is not entirely quantified. The aim of this study was to investigate the prevalence of parietal cell antibodies (PCA) in a large cohort of consecutive patients with AIT.We retrospectively studied 2016 consecutive women and 258 men with AIT seen at our referral center in the period from 2004 to 2008. All patients were screened for the presence of PCA in the serum.The prevalence of serum PCA in female patients was 29.7% and progressively increased from 13% in the first-second decade of life to peak at 42% in the ninth decade. During follow up, 21.1% of the PCA-positive patients converted to PCA-negative status. Mean (±standard deviation) basal PCA levels in this group were significantly lower (32 ± 28 U/mL) compared with those remaining PCA positive (129 ± 200 U/mL). A similar prevalence (29.8%) with a similar age-dependency was found in male patients.In conclusion, our study demonstrates a high, age-dependent prevalence of PCA in an unselected large population of patients with AIT.

Background and aims: Ghrelin is an orexigenic hormone produced in the stomach and in other organs, exerting a wide range of metabolic functions, including stimulation of GH secretion. Ghrelin secretion is decreased by iv or oral glucose load as well as during euglycemic-hyperinsulinemic clamp and hypoglycemia. We evaluated the circulating ghrelin levels in GH-deficient (GHD) and in GH-sufficient (GHS) patients during GHRH plus arginine test. Materials and methods: The study group comprised 35 patients, including 20 with pituitary tumors, 12 with empty sella, 2 with short stature, and 1 with post-traumatic isolated GH deficiency. According to the results of GHRH plus arginine test, 14 patients were defined as GHD and 21 as GHS. Patients with central hypothyroidism, hypocorticism, and hypogonadism had been on replacement therapy for at least 3 months at the moment of the study. Blood samples were collected every 20 min up to 60 min after GHRH and arginine administration. Results: By definition, GH response to GHRH plus arginine was higher in GHS than GHD group (p

Hypothyroid patients on l-T(4) therapy may require replacement doses exceeding the theoretical needs to normalize serum TSH due to low patient compliance, drugs interference, and malabsorption.We examined whether autoimmune gastritis might cause increased l-T(4) requirement in patients with autoimmune thyroiditis receiving l-T(4) replacement.We studied 391 patients with clinical or subclinical hypothyroidism from autoimmune thyroiditis who had achieved normal serum TSH concentration (0.3-3.0 microU/ml) under l-T(4) for at least 6 months. Patients were screened for serum parietal cell antibodies (PCA) as a marker of autoimmune gastritis, and the PCA status was correlated with the l-T(4) dose. We also studied a group of 60 patients receiving l-T(4) replacement after total thyroidectomy.PCA-positive (155 of 391) and PCA-negative (236 of 391) patients did not differ for pretherapy serum TSH levels and thyroid volume. The l-T(4) requirement was significantly (P = 0.002) higher in PCA-positive (1.24 +/- 0.40 microg/kg x d) than in PCA-negative patients (1.06 +/- 0.36 microg/kg x d), and a significant positive correlation was found between l-T(4) requirement and serum PCA levels. Among PCA-positive patients, l-T(4) requirement was even higher in those with proven gastritis (1.52 +/- 0.40 microg/kg x d) compared with those without gastric damage (1.15 +/- 0.33 microg/kg x d) (P0.0001). The increased l-T(4) requirement was confirmed also in PCA-positive thyroidectomized patients (1.81 +/- 0.27 microg/kg x d) compared with PCA-negative thyroidectomized patients (1.52 +/- 0.24 microg/kg x d). Independent variables affecting l-T(4) requirement were PCA and serum TSH at diagnosis.Autoimmune gastritis is an additional factor affecting l-T(4) requirement in patients with autoimmune thyroiditis. Serum PCA measurement should be considered in patients with an unexplained high requirement of l-T(4).

Autoimmune gastritis is frequently associated with autoimmune thyroiditis and other organ-specific autoimmune diseases, and may lead to atrophic body gastritis (ABG). We studied the diagnostic use of the measurement of serum ghrelin compared with other markers of gastric damage in predicting the presence of ABG in patients with autoimmune gastritis.We studied 233 patients with autoimmune gastritis and 211 control subjects. All patients and control subjects were screened for circulating parietal cell antibodies (PCAs) and were tested for serum ghrelin, gastrin, pepsinogen I and II, and anti-Helicobacter pylori antibody levels. A total of 52 patients and 28 control subjects underwent a gastric endoscopy.In PCA/positive patients, mean (+/-sd) serum ghrelin levels were significantly lower (238 +/- 107 pmol/liter), and mean (+/-sd) serum gastrin levels were significantly higher (81.2 +/- 128.3 ng/ml), with respect to PCA/negative patients (282 +/- 104 pmol/liter and 20.7 +/- 13.3 ng/ml, respectively; P0.0001). Serum ghrelin and gastrin levels were inversely correlated (P = 0.004). A total of 40 patients had ABG documented by the gastric biopsy (90% in PCA/positive patients and 10% in PCA/negative patients). The receiver operating characteristic curve analysis revealed that a cutoff value for serum ghrelin of 188 pmol/liter was associated with the highest sensitivity and specificity (97.3 and 100%, respectively) in detecting gastric atrophy and was superior to gastrin (P = 0.012), PCA (P = 0.002), and the pepsinogen I/II ratio (P = 0.016) measurements.Our study demonstrates that ghrelin secretion is negatively affected by autoimmune gastritis, and its serum level represents the most sensitive and specific noninvasive marker for selecting patients at high risk for ABG.

Cyclic Cushing's disease is an unusual disorder characterised by ACTH-dependent periodical increase of serum cortisol levels, clinically accompanied by peripheral edema, abnormalities of cardiac rhythm and hypokalemia. The condition may be unrecognised for years, since the typical features of Cushing's disease are usually absent due to the intermittent and brief duration of cortisol hypersecretion. We describe the case of a 42-yr-old man with Cyclic Cushing's disease due to an ACTH-producing pituitary macroadenoma, who presented two episodes of hypercortisolism in a 3-yr-period, clinically characterised by peripheral edema, hypokalemia and arrhythmia. The diagnosis was suspected because of a paradoxical increase of plasma ACTH and cortisol after dexamethasone administration during an asymptomatic period and was confirmed by pituitary imaging and by final histology after transphenoidal resection of the pituitary adenoma. After surgery, the patient resumed a normal pituitary-adrenal function with restoration of the normal ACTH and cortisol suppression after dexamethasone. Cyclic Cushing's disease should be considered in the differential diagnosis of several conditions characterised by recurrent episodes of idiopathic edema, hypokalemia or unexplained cardiac arrhythmia. In such patients, the pituitary-adrenal axis should be tested possibly during the acute phase of their disease or using the dexamethasone suppression test during asymptomatic intervals.