Latent Adrenal Insufficiency: From Concept to Diagnosis

Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.

Effects of Etomidate Combined With Dexmedetomidine on Adrenocortical Function in Elderly Patients: A Double-Blind Randomized Controlled Trial

Introduction Etomidate has been advocated to be used in anesthesia of the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the dose-dependent suppression of etomidate on adrenal cortex function leads to the limitation of its clinical application. Clinical research shows that dexmedetomidine can reduce the dose requirements for intravenous or inhalation anesthetics and opioids, and the hemodynamics is more stable during the operation. The objective is to observe the effect of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients. Methods 180 elder patients scheduled for elective ureteroscopic holmium laser lithotripsy were randomly allocated to PR group anesthetized with propofol- remifentanil, ER group anesthetized with etomidate-remifentanil, and ERD group anesthetized with dexmedetomidine combined with etomidate-remifentanil. Patients in each group whose operation time was less than or equal to 1h were incorporated into short time operation group (PR1 group, ER1 group and ERD1 group), and whose operation time was more than 1h were incorporated into long time operation group (PR2 group, ER2 group and ERD2 group). The values of SBP, DBP, HR and SpO2 were recorded at T0, T1, T2, T3, T4, T5, T6 and T7.The time of operation, the dosage of etomidate and remifentanil administrated during surgery, the time to spontaneous respiration, recovery and extubation, and the duration of stay in the PACU were recorded. The serum cortisol and ACTH concentration was measured at t0, t1, t2, t3, t4 and t5. Results The dosage of etomidate was significantly lower in ERD1 group and ERD2 group compared with ER1 group and ER2 group(P < 0.05), respectively. The SBP in ER2 and ERD2 group were higher at T1 and T3 compared to PR2 group (P < 0.05). The DBP in ER1 and ERD1 group were higher at T1compared to PR1 group (P < 0.05). The Serum cortisol concentration were higher at t1 ~ 2 in ERD1 group compared to ER1 group (P < 0.05). The Serum cortisol concentration were higher at t1 ~ 3 in ERD2 group compared to ER2 group (P < 0.05).The Serum ACTH concentration were lower at t1 ~ 2 in ERD1 group compared to ER1 group (P < 0.05). The Serum ACTH concentration were lower at t1 ~ 3 in ERD2 group compared to ER2 group (P < 0.05). Conclusion The administration of dexmedetomidine combined with etomidate can attenuate the inhibition of etomidate on adrenocortical function in elderly patients and maintain intraoperative hemodynamic stability.

Infectious Complications after Etomidate vs. Propofol for Induction of General Anesthesia in Cardiac Surgery—Results of a Retrospective, before–after Study

Background: Etomidate is typically used as an induction agent in cardiac surgery because it has little impact on hemodynamics. It is a known suppressor of adrenocortical function and may increase the risk for post-operative infections, sepsis, and mortality. The aim of this study was to evaluate whether etomidate increases the risk of postoperative sepsis (primary outcome) and infections (secondary outcome) compared to propofol. Methods: This was a retrospective before–after trial (IRB EA1/143/20) performed at a tertiary medical center in Berlin, Germany, between 10/2012 and 01/2015. Patients undergoing cardiac surgery were investigated within two observation intervals, during which etomidate and propofol were the sole induction agents. Results: One-thousand, four-hundred, and sixty-two patients, and 622 matched pairs, after caliper propensity-score matching, were included in the final analysis. Sepsis rates did not differ in the matched cohort (etomidate: 11.5% vs. propofol: 8.2%, p = 0.052). Patients in the etomidate interval were more likely to develop hospital-acquired pneumonia (etomidate: 18.6% vs. propofol: 14.0%, p = 0.031). Conclusion: Our study showed that a single-dose of etomidate is not statistically associated with higher postoperative sepsis rates after cardiac surgery, but is associated with a higher incidence of hospital-acquired pneumonia. However, there is a notable trend towards a higher sepsis rate.

Utility of Urinary Ratio of Cortisol to Aldosterone as Inflammatory and Metabolic Parameters

Corticosteroids are important bioactive substances in the body that regulate inflammation, metabolism, immunity, and circulatory dynamics. Cortisol and aldosterone are two major naturally occurring steroids, which synthesized in the adrenal fasciculata and in the adrenal glomerulosa under the regulation of adrenocorticotropin (ACTH) and renin-angiotensin system (RAS), respectively. The conventional strategy for evaluating adrenocortical function has been to measure random serum cortisol or 24-hour stored levels of urine free cortisol (UFC). UFC is a more appropriate marker to avoid the effects of diurnal fluctuation of cortisol, serum cortisol-binding proteins, and cortisol clearance in the kidney. Thus, measurement of UFC has been a reliable test for diagnosis of Cushing’s disease or adrenal insufficiency. However, since the normal range of UFC varies widely, it is often difficult to evaluate whether the UFC level is optimal or not for each patient. That is because UFC is greatly affected by the amount of fluid intake or urine volume, and an immunoassay for UFC, which is the usual method for measuring UFC, is susceptible to interference from other steroid metabolites and synthetic glucocorticoids. To explore an alternative indicator, we tried to standardize the levels of UFC by the levels of urinary aldosterone concentration (UAC) in the same urinary sample. Medical records of all 246 patients in whom daily excretions of UFC and UAC had been measured between 2015 and 2018 at our department were reviewed. 142 patients (including 93 females) were included after exclusion of 104 patients because of corticosteroid replacement therapy. UFC/UAC ratio showed significant positive and negative correlations with the levels of serum cortisol (R=0.287) and aldosterone (R=-0.762), respectively. UFC/UAC ratio increased with aging in female patients, while the ratio was not altered by the levels of BMI in either gender. Markers for metabolic and inflammatory status including hemoglobin A1c (R=0.327), albumin (R=-0.331), chorine esterase (R=-0.248), C-reactive protein (R=0.317), ferritin (R=0.473), and D-dimer (R=0.569) showed correlations to the ratio of UFC/UAC that were more significant than the correlations to the serum level of cortisol or UFC alone. Of note, the UFC/UAC ratio was shown as an indicator for risks of diabetes (AUC: 0.765), hypoalbuminemia (0.839), hyper-CRPemia (0.748), and thrombophilia (0.824), in which the cut-off levels of UFC/UAC ratios were found to be around 12. These results indicate that the UFC/UAC ratio is a suitable variable for the detection of metabolic and inflammatory complications related to adrenocortical dysfunction.