Are comorbidities of patients with adrenal incidentaloma tied to sex?

Background: A recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up. Methods: We retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months. Results: The rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p<0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p<0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sex-related pattern was observed. Conclusion: Patients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.

Application of Artificial Neural Networks (ANN) to Elucidate the Connections among Smell, Obesity with Related Metabolic Alterations, and Eating Habit in Patients with Weight Excess.

Obesity is a severe health problem linked to an increased risk of comorbidity and mortality and its etiopathogenesis includes genetic, epigenetic, microbiota composition, and environmental factors, such as dietary habits. The olfactory system plays an important role in controlling food intake and meal size, influencing body weight and energy balance. This study aims to identify the connection between olfactory function and clinical and nutritional aspects related to weight excess in a group of 68 patients with overweight or obesity. All participants underwent the evaluation of olfactory function, anthropometric data (weight, height, BMI, waist circumference), clinical data (hypertension, disglycemia, dyslipidemia, metabolic syndrome), and adherence to the Mediterranean diet (Mediterranean Diet Score). A fourth-generation artificial neural network data mining approach was used to uncover trends and subtle associations between variables. Olfactory tests showed that 65% of patients presented hyposmia. A negative correlation was found between olfactory scores and systolic blood pressure, fasting plasma glucose, and triglycerides levels, but a positive correlation was found between olfactory scores and the Mediterranean diet score. The methodology of artificial neural networks and the semantic connectivity map "Auto-Contractive Map" highlighted the underlying scheme of the connections between the variables considered. In particular, hyposmia was linked to obesity and related metabolic alterations and the male sex. The female sex was connected with normosmia, higher adherence to the Mediterranean diet, and normal values of blood pressure, lipids, and glucose levels. These results highlight an inverse correlation between olfactory skills and BMI and show that a normosmic condition, probably because of greater adherence to the Mediterranean diet, seems to protect not only from an excessive increase in body weight but also from associated pathological conditions such as hypertension and metabolic syndrome.

Perioperative Nutritional Management in Enhanced Recovery after Bariatric Surgery.

Obesity is a crucial health problem because it leads to several chronic diseases with an increased risk of mortality and it is very hard to reverse with conventional treatment including changes in lifestyle and pharmacotherapy. Bariatric surgery (BS), comprising a range of various surgical procedures that modify the digestive tract favouring weight loss, is considered the most effective medical intervention to counteract severe obesity, especially in the presence of metabolic comorbidities. The Enhanced Recovery After Bariatric Surgery (ERABS) protocols include a set of recommendations that can be applied before and after BS. The primary aim of ERABS protocols is to facilitate and expedite the recovery process while enhancing the overall effectiveness of bariatric procedures. ERABS protocols include indications about preoperative fasting as well as on how to feed the patient on the day of the intervention, and how to nourish and hydrate in the days after BS. This narrative review examines the application, the feasibility and the efficacy of ERABS protocols applied to the field of nutrition. We found that ERABS protocols, in particular not fasting the patient before the surgery, are often not correctly applied for reasons that are not evidence-based. Furthermore, we identified some gaps in the research about some practises that could be implemented in the presence of additional evidence.

Weight Maintenance after Dietary Weight Loss: Systematic Review and Meta-Analysis on the Effectiveness of Behavioural Intensive Intervention.

After a low-calorie diet, only 25% of patients succeed in maintaining the result of weight loss for a long time. This systematic review and meta-analysis aims to explore whether patients undergoing intensive intervention during the maintenance phase have a greater preservation of the weight achieved during the previous slimming phase than controls. A bibliographic search was conducted using PubMed, Scopus, and Cochrane databases for clinical trials and randomised, controlled trials investigating the role of choice in weight-loss-maintenance strategies. Only studies with a follow-up of at least 12 months were considered. A total of eight studies, for a total of 1454 patients, was identified, each comparing a group that followed a more intensive protocol to a control group. Our metanalysis highlighted that an intensive approach even in the maintenance phase could be important to ensure greater success in the phase following the weight-loss period. However, it should be pointed out that the improvement was not so different from the trend of the respective controls, with a non-statistically significant mean difference of the effect size (0.087; 95% CI -0.016 to 0.190 p = 0.098). This finding, along with the observation of a weight regain in half of the selected studies, suggests this is a long work that has to be started within the weight-loss phase and reinforced during the maintenance phase. The problem of weight control in patients with obesity should be understood as a process of education to a healthy lifestyle and a balanced diet to be integrated in the context of a multidisciplinary approach.

Dynamics of Gut Microbiota and Clinical Variables after Ketogenic and Mediterranean Diets in Drug-Naïve Patients with Type 2 Diabetes Mellitus and Obesity.

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile.

Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial.

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Nutritional Management in Bariatric Surgery Patients.

The obesity epidemic, mainly due to lifestyle changes in recent decades, leads to serious comorbidities that reduce life expectancy. This situation is affecting the health policies of many nations around the world. Traditional measures such as diet, physical activity, and drugs are often not enough to achieve weight loss goals and to maintain the results over time. Bariatric surgery (BS) includes various techniques, which favor rapid and sustained weight loss. BS is a useful and, in most cases, the best treatment in severe and complicated obesity. In addition, it has a greater benefit/risk ratio than non-surgical traditional therapies. BS can allow the obese patient to lose weight quickly compared with traditional lifestyle changes, and with a greater probability of maintaining the results. Moreover, BS promotes improvements in metabolic parameters, even diabetes remission, and in the quality of life. These changes can lead to an increase of life expectancy by over 6 years on average. The nutrition of people before and after BS must be the subject of indications from a trained staff, and patients must be followed in the subsequent years to reduce the risk of malnutrition and the associated problems. In particular, it is still debated whether it is necessary to lose weight prior to surgery, a procedure that can facilitate the surgeon's work reducing the surgical risk, but at the same time, lengthens preparation times increasing the risks associated with concomitant pathologies. Furthermore, preventing nutritional deficiencies prior to the intervention can improve the results and reduce short- and long-term mortality.

Diabetes insipidus secondary to nivolumab-induced neurohypophysitis and pituitary metastasis.

SUMMARY: A 62-year-old patient with metastatic hypopharyngeal carcinoma underwent treatment with nivolumab, following which he developed symptoms suggestive of diabetes insipidus. Nivolumab was stopped and therapy with methylprednisolone was started. During corticosteroid therapy, the patient presented himself in poor health condition with fungal infection and glycemic decompensation. Methylprednisolone dose was tapered off, leading to the resolution of mycosis and the restoration of glycemic compensation, nevertheless polyuria and polydipsia persisted. Increase in urine osmolarity after desmopressin administration was made diagnosing central diabetes insipidus as a possibility. The neuroradiological data by pituitary MRI scan with gadolinium was compatible with coexistence of metastatic localization and infundibulo-neurohypophysitis secondary to therapy with nivolumab. To define the exact etiology of the pituitary pathology, histological confirmation would have been necessary; however, unfortunately, it was not possible. In the absence of histological confirmation, we believe it is likely that both pathologies coexisted. LEARNING POINTS: A remarkable risk of endocrine immune-related adverse events (irAEs) during therapy with checkpoint inhibitors exsists. In order to ensure maximum efficiency in the recognition and treatment of endocrine iRAes related to immune checkpoint inhibitors, multidisciplinary management of oncological patients is critical. The pituitary syndrome in oncological patients who underwent immunotherapy represents a challenge in the differential diagnosis between pituitary metastasis and drug-induced hypophysitis. This is the first case, described in the literature of diabetes insipidus in a patient suffering from nivolumab-induced infundibulo-neurohypophysitis and anterohypophyseal metastasis.