Corticosteroid Management of Coronavirus 2019 (COVID-19) in Patients with Bilateral Adrenalectomy

Since the World Health Organization (WHO) announced coronavirus 2019 (COVID-19) as a pandemic in March 2020, it has been wreaking havoc across countries, affecting people’s lives. Corticosteroids have proven to provide a mortality benefit in patients with COVID-19. Although dexamethasone is the most commonly used glucocorticoid and have shown to have mortality benefit in COVID-19 patients, it cannot be used in patients with adrenal insufficiency due to its lack of mineralocorticoid activity. Herein, we discuss a case of challenging corticosteroid management in a patient with COVID-19 complicated by her medical history of bilateral adrenalectomy.

The main effects and application of glucocorticosteroids in clinical practice. A multidisciplinary approach

Glucocorticosteroids are hormones produced by the adrenal cortex. The term also refers to semi-synthetic drugs such as prednisolone, dexamethasone and other drugs that are derivatives of hydrocortisone, the most active natural glucocorticosteroid. Cortisone is a biologically inactive compound that is converted to hydrocortisone in the liver. Both natural glucocorticosteroids have mineralocorticoid activity, but weaker than genuine mineralocorticoids.

Examination of the association of steroids with fluid accumulation in critically ill patients, considering the possibility of biases

Glucocorticoids might have significant influence on positive fluid balance, mostly due to their mineralocorticoid effect. We assessed the association between glucocorticoid therapy and fluid balance in septic patients, in the intensive care unit (ICU). We considered two definitions of exposure: daily exposure to glucocorticoids and glucocorticoid treatment at any time. Of 945 patients, 375 were treated with glucocorticoids in the ICU. We applied four regression models. In the first, fluid balance did not differ during days with and without glucocorticoid treatment, among patients treated and not treated with glucocorticoids in the ICU. In our second model, daily fluid balance was increased in patients who were ever treated with glucocorticoids during their ICU stay compared to untreated patients. In the third model, which included only patients treated with glucocorticoids during their ICU stay, glucocorticoid treatment days were not associated with daily fluid balance. In the last model, on "steroid-free days", patients who received glucocorticoid treatment during their ICU stay had a positive fluid balance compared to those who were never treated with steroids. Despite their known mineralocorticoid activity, glucocorticoids themselves appear not to contribute substantially to fluid retention. This work highlights the importance of precise selection of variables to mitigate biases.

Low-dose steroid-induced bradyarrhythmias and treatment refractory hypokalaemia: a case report

Corticosteroid therapy has become an important modality of treatment for diseases in which rapid control of immunoinflammatory processes is required. However, one of the serious, but less known adverse effect of this therapy is cardiac arrhythmias. This includes both tachyarrhythmias and bradyarrhythmias. Corticosteroid use may also be associated with electrolyte imbalances like hypokalaemia by its mineralocorticoid activity. Those side effects are mainly seen with high-dose intravenous methyl-prednisolone or oral pulse dose prednisolone therapy. Here we report our experience in a child with warm idiopathic autoimmune haemolytic anaemia who developed sinus bradyarrhythmias and treatment refractory hypokalaemia during low-dose steroid therapy with reduction in heart rate by 60% of baseline.

The possible association of steroids with fluid accumulation in critically ill patients – a case of a potential bias

Background: Glucocorticoids (GCS) are commonly administered to critically ill patients. Due to their mineralocorticoid effect, GCS might have a substantial influence on a positive fluid balance. We assessed the association between glucocorticoids (GCS) therapy and fluid balance in critically ill patients with sepsis.Methods: This is a retrospective study of patients with sepsis hospitalized during 2006-2018 in a general intensive care unit (ICU) at a 1100-bed tertiary medical center.Results – We considered two definitions of exposure: daily exposure to GCS and GCS treatment at any time in the ICU. Of 945 patients with a diagnosis of sepsis, 375 were treated with GCS at any time and 570 were not. We applied four regression models to assess the association between GCS treatment and fluid balance; in our first model, fluid balance did not differ during days with GCS treatment, between patients who were and were not treated with GCS in the ICU (coefficient estimate 79.5 (-55.4 to 214.4), p=0.25). In our second model, daily fluid balance was increased by 139.8 ml (10.8 to 268.9; p=0.03) in patients who were ever treated with GCS during their ICU stay compared to untreated patients. In the third model, which included only patients treated with GCS during their ICU stay, GCS treatment days were not associated with daily fluid balance (coefficient estimate -190.6 (-485.1 to 103.9), p-value=0.21). In the last model, on "steroid free days", patients who received GCS treatment during their ICU stay had a positive fluid balance compared to those who were never treated with steroids (coefficient estimate 157.7 (-24.6 to 340.1), p-value=0.09).Conclusions – Despite their known mineralocorticoid activity, GCS themselves appear not to contribute substantially to fluid retention. The findings highlight the importance of a clear definition of exposure.

Proton Pump Inhibition in the Management of Hypokalemia in Anorexia Nervosa with Self-Induced Vomiting

Hypokalaemia is a dangerous complication in severe cases of eating disorders with self-induced vomiting and can result in rhabdomyolysis, cardiac arrhythmias, and death. Self-induced vomiting leads to hypokalaemia through two pathways. First, loss of gastric acid causes hypochloraemic metabolic alkalosis, which increases filtered bicarbonate load in the nephron (exceeding the tubular resorptive threshold), and subsequently increases distal sodium bicarbonate delivery. Secondly, hypovolaemia causes activation of the renin-angiotensin-aldosterone axis. Increased distal sodium delivery and mineralocorticoid activity together cause urinary potassium wasting. Standard management of severe hypokalaemia in patients with anorexia or bulimia nervosa and persistent self-induced vomiting includes intravenous replacement of potassium and correction of hypovolaemia. However, hypokalaemia is often refractory in eating disorder outpatients who have ongoing self-induced vomiting after discharge. We present a case of hypokalaemia due to anorexia nervosa, binge-purge subtype with self-induced vomiting successfully treated with a proton pump inhibitor (PPI) in addition to standard therapy.

Corticosteroids in the Management of Hyponatremia, Hypovolemia, and Vasospasm in Subarachnoid Hemorrhage: A Meta-Analysis

Background: Cerebral vasospasm and sodium and fluid imbalances are common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and cause of significant morbidity and mortality. Studies have shown the benefit of corticosteroids in the management of these sequelae. We have reviewed the literature and analyzed the available data for corticosteroid use after SAH. Methods: PubMed, EMBASE, and Cochrane electronic databases were searched without language restrictions, and 7 observational, controlled clinical studies of the effect of corticosteroids in the management of SAH patients were identified. Data on sodium and fluid balances, symptomatic vasospasm (SVS), and outcomes were pooled for meta-analyses using the Mantel-Haenszel random effects model. Results: Corticosteroids, specifically hydrocortisone and fludrocortisone, decreased natriuretic diuresis and incidence of hypovolemia. Corticosteroid administration is associated with lower incidence of SVS in the absence of nimodipine, but does not alter the neurological outcome. Conclusions: Supplementation of corticosteroids with mineralocorticoid activity, such as hydrocortisone or fludrocortisone, helps in maintaining sodium and volume homeostasis in SAH patients. Larger trials are warranted to confirm the effects of corticosteroids on SVS and patient outcomes.

Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans

Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal and distal tubule acidification in experimental animals both directly and indirectly via increased mineralocorticoid activity. Diet-induced acid loads have been shown to increase renal endothelin-1 activity, and it is hypothesized that increased dietary acid-induced endothelin-1 activity may be a causative progression factor in human renal insufficiency and that this might be reversed by provision of dietary alkali. We sought to clarify, in normal human volunteers, the role of endothelin-1 in renal acidification and to determine whether the effect is dependent on dietary sodium chloride. Acid-base equilibrium was studied in seven normal human volunteers with experimentally induced metabolic acidosis [NH4Cl 2.1 mmol·kg body weight (BW)−1·day−1] with and without inhibition of endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist bosentan (125 BID p.o./day) both during dietary NaCl restriction (20 mmol/day) and NaCl repletion (2 mmol NaCl·kg BW−1·day−1). During NaCl restriction, but not in the NaCl replete state, bosentan significantly increased renal net acid excretion in association with stimulation of ammoniagenesis resulting in a significantly increased plasma bicarbonate concentration (19.0 ± 0.8 to 20.1 ± 0.9 mmol/l) despite a decrease in mineralocorticoid activity and an increase in endogenous acid production. In pre-existing human metabolic acidosis, endothelin-1 activity worsens acidosis by decreasing the set-point for renal regulation of plasma bicarbonate concentration, but only when dietary NaCl provision is restricted.

The Role of Steroids in Endothelial Function in the Aging Male

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion, and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during aging and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade, more attention has been drawn to the importance of testosterone, estradiol and adrenal androgens in the pathophysiology, prevention, and treatment of male aging-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and that their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the aging male are frequent and may yield endothelial dysfunction and increased cardiovascular burden. We recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidemia.