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IntroductionBioelectrical impedance analysis (BIA) is the most used tool in clinical practice to evaluate body composition in patients with obesity. The skeletal muscle index (SMI) defined by BIA has been proposed for the identification of sarcopenia, but there are currently no univocal cutoffs for this condition. In this study, we aimed: 1) to determine the prevalence of sarcopenia in patients with severe obesity using the current cutoffs of SMI; 2) to define new specific cutoffs; 3) to validate the new cutoffs; and 4) to re-determine the prevalence of sarcopenia.MethodsA total of 300 patients, 74% women and 26% men (mean age = 42.6 ±; 9 years), with morbid obesity (mean BMI = 46.7 ±; 6.5 kg/m2) followed by the Unit of Endocrinology from January 2014 to December 2020 were retrospectively evaluated. SMI was calculated as the skeletal muscle mass normalized for squared height through the BIA equation by Janssen et al.ResultsThe prevalence of sarcopenic obesity calculated using the cutoff points reported by De Rosa et al. (7.3 kg/h2 for women and 9.5 kg/h2 for men) was 2.3%. The prevalence of sarcopenia was calculated using the new cutoffs: with the cutoff obtained from the standard deviation method (8.2 kg/h2 for women and 10.2 kg/h2 for men), a prevalence of 14.7% was observed, whereas the prevalence reached 47.6% when using the cutoff calculated through the K-means unsupervised cluster (9.2 kg/h2 for women and 11.3 kg/h2 for men). The new cutoffs were validated with a second sample consisting of 300 patients with morbid obesity (BMI = 44.9 ±; 6.7 kg/m2): the rate of sarcopenic patients was still higher than that observed in the training cohort (56%). After the matching procedure (by BMI and age), the rates of sarcopenic patients were similar in both groups (50.2% in the validation group and 53% in the training group, p = 0.6).ConclusionThe new cutoffs calculated with cluster analysis could better identify sarcopenia in morbidly obese patients. However, further studies are needed to validate these cutoffs in different patient cohorts.

Abstract 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.

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.

ABSTRACT: 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

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.

Background: Liraglutide is a once-daily injectable medication approved for the treatment of obesity. Hereby we report the feasibility, 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 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 ~50% of our sample, followed up for a period of 180 days. Larger, longer, controlled, prospective studies are warranted.

Background: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.Methods: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.Results: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.Conclusions:In conclusion, our study demonstrates a high, age-dependent prevalence of PCA in an unselected large population of patients with AIT. [ABSTRACT FROM AUTHOR]