Emergency treatment of adrenal crisis with prednisone suppositories: a bioequivalence study in female patients with Addison’s disease

Objective: Patients with adrenal insufficiency (AI) need to adapt their glucocorticoid replacement under stressful conditions to prevent adrenal crisis s (AC). Prednisone (PN) suppositories are used for emergency treatment. Pharmacokinetics of 100 mg PN suppositories after vaginal or rectal administration was evaluated. Design: Single-center, open-label, sequence-randomized, cross-over, bioequivalence study. Methods: Twelve females with primary AI were included. Comparison of pharmacokinetics after vaginal and rectal administration of 100 mg PN suppositories. Main outcome measures: bioequivalence (Cmax: maximum plasma concentration of prednisolone; AUC0–360: area under the plasma concentration curve of prednisolone from administration to 360 min), adrenocorticotropin (ACTH) levels, safety and tolerability. Comparison of ACTH-suppressive effect with subcutaneous and intramuscular administration of 100 mg hydrocortisone. Results: Vaginal administration of PN suppositories was not bioequivalent to rectal administration: Cmax and AUC0–360 were significantly lower after vaginal compared to rectal administration: 22 ng/mL (109%) vs 161 ng/mL (28%), P 50% of baseline values was observed 149 min (32%) after rectal PN administration; after vaginal PN administration, the maximum decrease within 360 min was only 44%. Adverse events were more frequent after vaginal administration and mainly attributable to the glucocorticoid deficit due to inadequate vaginal absorption. The ACTH-suppressive effect was more pronounced after parenteral hydrocortisone compared to rectal or vaginal PN. Conclusion: Vaginal administration of PN suppositories in the available form is not useful for prevention of AC. Pharmacokinetics after rectal use of PN s how inferiority compared to available data on parenteral glucocorticoids. In adrenal emergencies, hydrocortisone injection should be the first choice

Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card!

Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients’ self-sustainability, education on how to tackle an ad renal crisis is crucial. All patients should carry the European Emergency Card

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing’s syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison’s disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules

Adrenal insufficiency.

Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production. Primary AI (PAI) is rare and is caused by direct adrenal failure. Secondary AI (SAI) is more frequent and is caused by diseases affecting the pituitary, whereas in tertiary AI (TAI), the hypothalamus is affected. The most prevalent form is TAI owing to exogenous glucocorticoid use. Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors and aldosterone (especially in PAI). Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones and stimulation tests. The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs. This Primer provides insights into the epidemiology, mechanisms and management of AI during pregnancy as well as challenges of long-term management. In addition, the importance of identifying life-threatening adrenal emergencies (acute AI and adrenal crisis) is highlighted and strategies for prevention, which include patient education, glucocorticoid emergency cards and injection kits, are described

Worsening of lipid metabolism after successful treatment of primary aldosteronism

Primary aldosteronism (PA) describes the most frequent cause of secondary arterial hypertension. Recently, deterioration of lipid metabolism after adrenalectomy (ADX) for aldosterone-producing adenoma (APA) has been described. We analysed longitudinal changes in lipid profiles in a large prospective cohort of PA patients. Data of 215 consecutive PA patients with APA (n = 144) or bilateral idiopathic adrenal hyperplasia (IHA, n = 71) were extracted from the database of the German Conn's Registry. Patients were investigated before and 1 year after successful treatment by ADX or by mineralocorticoid receptor antagonists (MRA). Glomerular filtration rate (GFR), fasting plasma glucose and components of lipid metabolism including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined at 8.00 after a 12-h fasting period. One year after initiation of treatment mean serum potassium levels and blood pressure normalized in the patients. HDL-C and TG developed inversely with decreasing HDL-C levels in patients with APA (p = .046) and IHA (p = .004) and increasing TG levels (APA p = .000; IHA p = .020). BMI remained unchanged and fasting plasma glucose improved in patients with APA (p = .004). Furthermore, there was a significant decrease of GFR in both subgroups at follow-up (p = .000). Changes in HDL-C and TG correlated with decrease in GFR in multivariate analysis (p = .024). Treatment of PA is associated with a deterioration of lipid parameters despite stable BMI and improved fasting plasma glucose and blood pressure. This effect can be explained by renal dysfunction following ADX or MRA therapy