Late-onset Schmidt's Syndrome Presenting with Severe Hyponatremia: A Case Report.

BACKGROUND: Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign. CASE REPORT: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies. CONCLUSIONS: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

From Adenoma to Carcinoma: the Unexpected Evolution of an Apparently Stable Adrenal Lesion.

BACKGROUND: There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma. CASE REPORT: The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease. CONCLUSION: Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].

COVID-19 vaccines and blood glucose control: Friend or foe?

PURPOSE: To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control. METHODS: Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM). RESULTS: It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia. CONCLUSIONS: Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.

Real-World Effectiveness of Denosumab and Bisphosphonates on Risk of Vertebral Fractures in Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors.

Bone-active drugs are recommended to protect the skeleton from detrimental actions of aromatase inhibitors (AIs). However, most of literature data are focused on bone mineral density (BMD), whereas data on fractures are scant. The aim of this prospective study was to investigate the real-life effectiveness of denosumab, oral bisphosphonates (BPs) and intravenous zoledronate on risk of vertebral fractures (VFs) induced by AIs. 567 consecutive women (median age 62 years, range 28-83) with early breast cancer undergoing treatment with AIs were evaluated for morphometric VFs and BMD at baseline and after 18-24 months of follow-up. After enrollment, 268 women (47.3%) started denosumab 60 mg subcutaneously every 6 months, 115 (20.3%) BPs (59 with oral BPs and, 56 with intravenous zoledronate 5 mg/12 months), whereas 184 women (32.5%) were not treated with bone-active drugs for several reasons. During follow-up, 54 women (9.5%) developed incident VFs in association with age of subjects (P < 0.001), baseline FRAX scores for major fractures (P < 0.001) and hip fractures (P = 0.003), pre-existing VFs (P < 0.001), change in BMD at lumbar spine (P = 0.015), femoral neck (P = 0.003) and total hip (P < 0.001). Risk of VFs was higher in subjects who were untreated as compared to those treated with bone-active drugs (32/184 vs. 22/383; P < 0.001). Specifically, fracture risk was significantly decreased by denosumab [odds ratio (OR) 0.22; P < 0.001] and zoledronate (OR 0.27; P = 0.035), but not by oral BPs (P = 0.317). These data suggest that in real-world clinical practice, denosumab and zoledronate can reduce AI-related risk of VFs after only 24 months of treatment.

Targeting microbiota in dietary obesity management: a systematic review on randomized control trials in adults.

Obesity is an alarming public health problem. Tailored nutritional therapy is advisable since emerging evidence on complex cross-talks among multifactorial agents. In this picture, the gut microbiota is highly individualized and intricately dependent on dietary patterns, with implications for obesity management. Most of the papers on the topic are observational and often conflicting. This review aimed to systematically organize the body of evidence on microbiota deriving from dietary trials in adult obesity giving the most certain phylogenetic, and metabolomic signatures in relation to both the host metabolism and phenotype changes published until now. We retrieved 18 randomized control trials on 1385 subjects with obesity who underwent several dietary interventions, including standard diet and healthy dietary regimens. Some phyla and species were more related to diets rich in fibers and others to healthy diets. Weight loss, metabolism improvements, inflammatory markers decrease were specifically related to different microorganisms or functions. The Prevotella/Bacteroides ratio was one of the most reported predictors. People with the burden of obesity comorbidities had the most significant taxonomic changes in parallel with a general improvement. These data emphasize the possibility of using symbiotic approaches involving tailored diets, microbiota characteristics, and maybe drugs to treat obesity and metabolic disorders. We encourage Authors to search for specific phylogenetic associations beyond a too generally reported Firmicutes/Bacteroides ratio.

Breakfast Skipping, Weight, Cardiometabolic Risk, and Nutrition Quality in Children and Adolescents: A Systematic Review of Randomized Controlled and Intervention Longitudinal Trials.

Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months. We searched relevant databases (2000-2021) and identified 584 articles, of which 16 were suitable for inclusion. Overall, 50,066 children and adolescents were included. No studies analyzed cardiometabolic features. Interventions were efficacious in reducing breakfast skipping prevalence when multi-level approaches were used. Two longitudinal studies reported a high prevalence of OW/OB in breakfast skippers, whereas RCTs had negligible effects. Ten studies reported a lower-quality dietary intake in breakfast skippers. This review provides insight into the fact that breakfast skipping is a modifiable marker of the risk of OW/OB and unhealthy nutritional habits in children and adolescents. Further long-term multi-level intervention studies are needed to investigate the relationship between breakfast, nutrition quality, chronotypes, and cardiometabolic risk in youths.

Regulation of GH and GH Signaling by Nutrients.

Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.