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Purpose The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. Methods This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. Conclusion This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)—Diet Therapies in Endocrinology and Metabolism.

Traumatic brain injury (TBI) is an important public health problem with an increasing incidence in the last years. Relatively few cases are fatal; most individuals will survive and, in the long-term, the sequalae of TBI will include neuroendocrine dysfunctions with a much higher frequency than previously suspected. Patients who develop hypopituitarism after TBI present manifestations due to the number of deficient hormones, severity of hormonal deficiency, and the duration of hypopituitarism without diagnosis and treatment. The clinical spectrum of hypopituitarism is very large and many signs and symptoms of TBI survivors such as fatigue, concentration difficulties, depressive symptoms are nonspecific and overlap with symptoms of post-traumatic stress disorder and variably severe hypopituitarism related to brain damage remaining undiagnosed. This can explain why the diagnosis of hypopituitarism is often missed or delayed after this condition with potentially serious and hazardous consequences for the affected patients. Moreover, clinical experience cumulatively suggests that TBI-associated hypopituitarism is associated with poor recovery and worse outcome, since post-traumatic hypopituitarism is independently associated with cognitive impairment, poor quality of life, abnormal body composition, and adverse metabolic profile. In the present review, the current data related to clinical consequences of pituitary dysfunction after TBI in adult patients and therapeutic approaches are reported.

Purpose Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function. Conclusion This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition – Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals “KetoNut-SINut” ; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis. Graphical abstract

Purpose To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. Methods Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007–2020) were retrospective evaluated. Results The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor’s surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. Conclusion This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed “one-size-fits-all model” is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Purpose Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in MEN1 tumor suppressor gene. Diagnosis is commonly based on clinical criteria and confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects. Methods While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the MEN1 gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses. Results NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of MEN1 gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient’s clinical phenotype, pointed toward a possible causative role. Conclusion Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.

Purpose The uncertainty on the management of small adrenal incidentalomas (AIs) still represents a challenge in real clinical practice. Considering the lack of knowledge on risk factors implicated in tumour enlargement, the aim of this study was to identify risk factors for morphological changes during follow-up of adrenal incidentalomas (AIs). Methods We retrospectively evaluated demographic, clinical, radiological and biochemical parameters of 153 AIs (2007–2021). Patients with histological diagnosis of metastases or pheochromocytoma were excluded. To detect risk factors for tumor enlargement, diseases associated with AIs were included if their prevalence was higher than 2%. Patients were divided into two groups (A: radiological stability; B: tumor enlargement defined as > 5 mm/year in the main diameter). Results Group A: 89.5% and group B: 10.5%, mean follow-up 38.6 ± 6.9 months (range 6–240). Tumor enlargement when occurred was within 36 months of follow-up. In group B high body weight ( p  < 0.03), dehydroepiandrosterone sulfate (DHEAS) ( p  < 0.05) and direct renin concentration (DRC) ( p  < 0.04) were higher than group A, while aldosterone levels were lower; moreover, considering comorbidities, glaucoma and dysglycemia ( p  < 0.01 for both) had higher prevalence in group B. Glaucoma and dysglycemia were independent predictors of enlargement. Patients affected by glaucoma, atrial fibrillation, dysglycemia had a lower dimensional change-free survival than non-affected. Conclusions Glaucoma might be a novel risk factor for AI enlargement. If subtle undetectable cortisol hypersecretion has a role is a topic for further research.

Aim. To evaluate clinical characteristics and perinatal outcomes in a heterogeneous population of Caucasians born in Italy and High Migration Pressure Countries (HMPC) women with GDM living in Piedmont, North Italy. Methods. We retrospectively analyzed data from 586 women referring to our unit (2015–2020). Epidemiological (age and country of origin) and clinical-metabolic features (height, weight, family history of DM, parity, previous history of GDM, OGTT results, and GDM treatment) were collected. The database of certificates of care at delivery was consulted in relation to neonatal/maternal complications (rates of caesarean sections, APGAR score, fetal malformations, and neonatal anthropometry). Results. 43.2% of women came from HMPC; they were younger p<0.0001 and required insulin treatment more frequently than Caucasian women born in Italy (χ2 = 17.8, p=0.007). Higher fasting and 120-minute OGTT levels and gestational BMI increased the risk of insulin treatment (OGTT T0: OR = 1.04, CI 95% 1.016–1.060, p=0.005; OGTT T120: OR = 1.01, CI 95% 1.002–1.020, p=0.02; BMI: OR = 1.089, CI 95% 1.051–1.129, p<0.0001). Moreover, two or more diagnostic OGTT glucose levels doubled the risk of insulin therapy (OR = 2.03, IC 95% 1.145–3.612, p=0.016). We did not find any association between ethnicities and neonatal/maternal complications. Conclusions. In our multiethnic GDM population, the need for intensive care and insulin treatment is high in HPMC women although the frequency of adverse peripartum and newborn outcomes does not vary among ethnic groups. The need for insulin therapy should be related to different genetic backgrounds, dietary habits, and Nutrition Transition phenomena. Thus, nutritional intervention and insulin treatment need to be tailored.

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale—GCS, Glasgow outcome scale—GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the “Regina Margherita” Hospital, in Turin and “Maggiore della Carità Hospital” in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

Abstract Disclosure: N. Filigheddu: None. T. Raiteri: None. S. Reano: None. A. Scircoli: None. A. Antonioli: None. F. Prodam: None. Vitamin D binding protein (VDBP), encoded by the Gc gene, is a multifunctional serum glycoprotein synthesized by hepatocytes, whose primary function is the transport of vitamin D metabolites in the bloodstream. In addition, VDBP enhances the chemotactic activity of neutrophil chemoattractants and takes part in the actin-scavenger system by acting as a monomeric G-actin-binding protein. Several studies have reported a correlation between increased levels of VDBP and various pathologies often associated with muscle wasting, including different types of tumors. Given these findings, we hypothesized that VDBP may play a role in skeletal muscle homeostasis.In vitro, treatment of C2C12 myotubes with 100 mM VDBP for 24 h induced the perturbation of intracellular actin dynamics due to VDBP's ability to bind G-actin that, in turn, led to mitochondrial dysfunction (i.e., mitochondrial membrane potential dissipation, respiratory impairment, increased ROS production, induction of the fission machinery), exacerbation of autophagy, and, eventually, atrophy, seen as the reduction of myotube diameter. Remarkably, pharmacological intervention on myotubes with jasplakinolide (250 mM, 30 min pre-treatment) to counteract VDBP effects on intracellular actin dynamics was sufficient to prevent VDBP-induced atrophy. To assess if VDBP had a causative role in muscle atrophy in vivo, we injected VDBP (1.5 mg/Kg) every 48 h for one week in the tibialis anterior muscles of Gc knock-out mice (VDBP KO). At the end of the experimental period, we observed the induction of the mitophagic gene Bnip3, impairment of muscle performances (26% reduction of grip strength at the endpoint), and a 16% reduction of muscle mass compared to the saline-injected contralateral muscles, confirming the atrophic effect of VDBP in vivo.Coherently with the upregulation of VDBP observed in cancer patients, VDBP levels also increase in murine models of cancer cachexia. To test the hypothesis that VDBP could play a role in cancer-associated muscle wasting, we induced cancer cachexia in VDBP KO mice by inoculating 106 Lewis Lung Carcinoma (LLC) cells resuspended in 100 μl of saline on the back of mice. Tumor-bearing VDBP KO mice preserved their body weight and performances, and the muscle loss was lessened by more than 50% compared to cachectic WT mice. Notably, between the two groups, there were no differences in tumor growth or food intake, ruling out the possibility that the reduction in muscle wasting could depend on smaller tumors or differential development of anorexia in the two genotypes. In conclusion, we demonstrated that VDBP acts as a hormone per se, having a direct pro-atrophic activity on skeletal muscle. Our data suggest that VDBP could represent a potential therapeutic target to treat cancer cachexia and other pathologies in which the rise of VDBP could impinge muscle mass and functionality. Presentation: 6/1/2024

•48.3% of children in Novara has been treated with CAM at least once in life.•81.5% of pediatricians prescribes CAM, particularly herbal medicine and homeopathy, but only the 13,6% of them have received a specific training.•CAM are mostly used to treat pathologies of ear, nose and throat. To examine prevalence and modalities of CAM use in children living in Novara, a northern Italian city, and to estimate the prescription rate from paediatricians. We administered a phone questionnaire to the parents of a sample of 147 children, asking questions about CAM use, children’s health profile, parental socio-economic status, use modalities, effectiveness perceptions, and motivations. A parallel survey was conducted by e-mail by investigating family paediatricians attitudes about CAM. Among 147 children whose families responded to our survey 48.3% was treated with CAM at least once in life and 38,1% during the previous year. Children treated with CAM were on average younger than those who were not. The types of CAM used were herbal medicine and homeopathy. Parents who choose CAM for their children were more skeptical about vaccinations. CAM were most frequently used to treat pathologies of ear, nose and throat. 85.9% of parents was willing to use CAM in future, 78.9% would pass to conventional medicine if CAM failed. Among paediatricians 81.5% prescribed CAM at least once, but only 13.6% received specific CAM training. The prevalence of children using CAM in Novara is high, in line with investigations conducted in Northern European countries. The distribution of pathologies treated with CAM, parental socio-economic status and general scepticism towards vaccination are consistent with the literature. Physicians should keep themselves up-to-date also about evidence-based CAM therapies and, most importantly, should have an open dialogue about CAM with their patients.