Corticoided

Myriad questions regarding perioperative management of patients on glucocorticoids (GCs) continue to be debated including which patients are at risk for adrenal insufficiency (AI), what is the correct dose and duration of supplemental GCs, or are they necessary for everyone? These questions remain partly unanswered due to the heterogeneity and low quality of data, studies with small sample sizes, and the limited number of randomized trials. To date, we know that although all routes of GC administration can result in hypothalamic-pituitary-adrenal (HPA) axis suppression, perioperative adrenal crisis is rare...

Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, and recruitment of functional transcriptional machinery...

Dual-release hydrocortisone is a new hydrocortisone formulation developed to improve the pharmacokinetic and the pharmacodynamic profiles and patient compliance. The aim of this review is to summarize the main knowledge on dual-release hydrocortisone, with particular attention to pharmacokinetics, metabolic and health-related quality-of-life aspects, bone health and drug safety.

Glucocorticoids are frequently prescribed to patients with a wide range of inflammatory and autoimmune diseases. The semi-synthetic glucocorticoid prednisolone is most commonly prescribed and in two main patterns. Prednisolone is prescribed short-term at medium-high doses to treat an acute inflammatory illness or long-term at lower doses to attenuate chronic inflammatory disease progression. In hospitalized patients with acute prednisolone-induced hyperglycaemia there is a distinct circadian pattern of glucose elevation, which occurs predominantly in the afternoon and evening...

Glucocorticoid hormones are a powerful mammalian systemic hormonal signal that exerts regulatory effects on almost every cell and system of the body. Glucocorticoids act in a circadian and stress-directed manner to aid in adaptation to an ever-changing environment. Circadian glucocorticoid secretion provides for a daily waxing and waning influence on target cell function. In addition, the daily circadian peak of glucocorticoid secretion serves as a timing signal that helps entrain intrinsic molecular clock phase in tissue cells distributed throughout the body...

Following the discovery of glucocorticoid receptors in the hippocampus and other brain regions, research has focused on understanding the effects of glucocorticoids in the brain and their role in regulating emotion and cognition. Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Allostatic overload, which can occur during chronic stress, can reshape the hypothalamic-pituitary-adrenal axis through epigenetic modification of genes in the hippocampus, hypothalamus and other stress-responsive brain regions...

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Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...

Unlocking the therapeutic potential of the glucocorticoid receptor (GR) has motivated a search for small molecules that selectively modulate its ability to activate or repress gene transcription. Recently, breakthrough studies in the field of genomics have reinvigorated debate over longstanding transcriptional models explaining how GR controls tissue-specific gene expression. Here, we highlight these genomic studies with the dual goals of advancing understanding of nuclear receptor-mediated transcription and stimulating thought on the development of anti-inflammatory and immunosuppressive ligands for GR that have reduced harmful effects on metabolism...

OBJECTIVE: Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. METHODS: Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations...

Antenatal glucocorticoid has proven to be one of the most successful single therapeutic approaches for preventing serious consequences after preterm birth. The fetal compartment is protected against endogenous corticosteroid by the high endogenous 11β-hydroxysteroid dehydrogenase type 2 that converts cortisol to cortisone and by the poor responsiveness of the fetal hypothalamus to corticotropin-releasing hormone. High corticosteroid activity acutely enhances the functional maturity of the fetus. Persistently high fetal glucocorticoid activity has adverse effects on the growth and differentiation of the fetal brain and other organs...

Based on molecular mechanisms and physiologic data, a strong association has been established between dysregulated systemic inflammation and progression of acute respiratory distress syndrome (ARDS). In ARDS patients, glucocorticoid receptor-mediated downregulation of systemic inflammation is essential to restore homeostasis, decrease morbidity and improve survival and can be significantly enhanced with prolonged low-to-moderate dose glucocorticoid treatment. A large body of evidence supports a strong association between prolonged glucocorticoid treatment-induced downregulation of the inflammatory response and improvement in pulmonary and extrapulmonary physiology...

Steroids have a plausible mechanism of action of reducing severity of lung disease in acute respiratory distress syndrome (ARDS) but have failed to show consistent benefits in patient-centered outcomes. Many studies have confounding from the likely presence of ventilator-induced lung injury and steroids may have shown benefit because administration minimized ongoing inflammation incited by injurious ventilator settings. If steroids have benefit, it is likely for specific populations that fall within the heterogeneous diagnosis of ARDS...

Systemic inflammation and duration of immobilization are strong independent risk factors for the development of intensive care unit-acquired weakness (ICUAW). Activation of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB) results in muscle wasting during disuse-induced skeletal muscle atrophy (ICU bed rest) and septic shock. In addition, NF-κB-mediated signaling plays a significant role in mechanical ventilation-induced diaphragmatic atrophy and contractile dysfunction. Older trials investigating high dose glucocorticoid treatment reported a lack of a sustained anti-inflammatory effects and an association with ICUAW...

Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic-pituitary-adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol...

Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has long been recognized that this 24-hour rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus...

Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone...