Mesenchymal Stem Cells Exposed to Persistently High Glucocorticoid Levels Develop Insulin-Resistance and Altered Lipolysis: A Promising In Vitro Model to Study Cushing's Syndrome.

Background: In Cushing's syndrome (CS), chronic glucocorticoid excess (GC) and disrupted circadian rhythm lead to insulin resistance (IR), diabetes mellitus, dyslipidaemia and cardiovascular comorbidities. As undifferentiated, self-renewing progenitors of adipocytes, mesenchymal stem cells (MSCs) may display the detrimental effects of excess GC, thus revealing a promising model to study the molecular mechanisms underlying the metabolic complications of CS. Methods: MSCs isolated from the abdominal skin of healthy subjects were treated thrice daily with GCs according to two different regimens: lower, circadian-decreasing (Lower, Decreasing Exposure, LDE) versus persistently higher doses (Higher, Constant Exposure, HCE), aimed at mimicking either the physiological condition or CS, respectively. Subsequently, MSCs were stimulated with insulin and glucose thrice daily, resembling food uptake and both glucose uptake/GLUT-4 translocation and the expression of LIPE, ATGL, IL-6 and TNF-α genes were analyzed at predefined timepoints over three days. Results: LDE to GCs did not impair glucose uptake by MSCs, whereas HCE significantly decreased glucose uptake by MSCs only when prolonged. Persistent signs of IR occurred after 30 hours of HCE to GCs. Compared to LDE, MSCs experiencing HCE to GCs showed a downregulation of lipolysis-related genes in the acute period, followed by overexpression once IR was established. Conclusions: Preserving circadian GC rhythmicity is crucial to prevent the occurrence of metabolic alterations. Similar to mature adipocytes, MSCs suffer from IR and impaired lipolysis due to chronic GC excess: MSCs could represent a reliable model to track the mechanisms involved in GC-induced IR throughout cellular differentiation.

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia.

OBJECTIVE: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on coronavirus disease-19 (COVID-19)-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact. STUDY DESIGN AND METHODS: 117 patients (81 males, 64 ± 13 years) hospitalized for COVID-19 between 1 March and 30 April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurements, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death. RESULTS: At admission, 26.5% patients had hyponatremia, and 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders ('mixed dysnatremia'). Lower sodium levels at admission were correlated with higher C reactive protein (CRP) (P = 0.039) and serum lactate levels (P = 0.019), but not interleukin-6 (IL-6). Hypernatremia and a wider sodium variability were associated with maximum required ventilation, need for ICU assistance and duration of the hospitalization. Mean estimated time to Intensive Care Unit (ICU) admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (log-rank test P = 0.032). CONCLUSIONS: Sodium alterations frequently affect hospitalized COVID-19 patients. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and the need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients' prognosis.

Hypothalamic-Pituitary Diseases and Erectile Dysfunction.

Several hormones contribute to ensure penile erection, a neurovascular phenomenon in which nitric oxide plays a major role. Erectile dysfunction (ED), which is defined as the persistent inability to obtain or maintain penile erection sufficient for a satisfactory sexual performance, may be due to arteriogenic, neurogenic, iatrogenic, but also endocrinological causes. The hypothalamus-pituitary axis plays a central role in the endocrine system and represents a fundamental link between the brain and peripheral glands, including gonads. Therefore, the hormonal production of the hypothalamic-pituitary axis can control various aspects of sexual function and its dysregulation can compromise erectile function. In addition, excess and deficiency of pituitary hormones or metabolic alterations that are associated with some pituitary diseases (e.g., Cushing's disease and acromegaly, hypopituitarism) can determine the development of ED with different mechanisms. Thus, the present review aimed to explore the relationship between hypothalamic and pituitary diseases based on the most recent clinical and experimental evidence.