The existence of adrenal insufficiency in patients with COVID-19 pneumonia.

Introduction: Infection with SARS-CoV-2 virus may result in long COVID, a syndrome characterized by symptoms such as dyspnea, cardiac abnormalities, cognitive impairment, and fatigue. One potential explanation for these symptoms is hypocortisolism. Objective: To evaluate the prevalence of hypocortisolism in patients with a history of COVID-19 pneumonia. Methods: Cross-sectional study of patients who were aged ≥18 years and had a 3-month history of radiography-confirmed COVID-19 pneumonia. Exclusion criteria included current or previous treatment with glucocorticoids and use of an oral contraceptive. Adrenal function was evaluated using a low dose (1ug) corticotropin stimulation test (CST). Serum cortisol levels were measured at 0, 30, and 60 minutes, and baseline plasma ACTH was also measured. Results: Of the 41 patients enrolled, the median age was 62 years, 17 (42%) were female, and all 41 (100%) had severe pneumonia at baseline. Eleven patients (27%) had hypocortisolism, as evidenced by peak cortisol of less than 402.81 nmol/l after low dose (1 µg) CST. Of these 11 patients, 10 (91%) had secondary hypocortisolism (median ACTH 6.27 pmol/L, range 4.98-9.95 pmol/L) and one had primary hypocortisolism (mean ACTH 32.78 pmol/L). Six of the 11 patients with hypocortisolism (54.5%) reported symptoms of persistent fatigue and 5 (45.5%) required regular glucocorticoid replacement. Conclusions: Our results suggest that hypocortisolism, predominantly caused by pituitary disruption, may emerge after SARS-CoV-2 infection and should be considered in patients with a history of COVID-19 pneumonia with or without clinical hypocortisolism.

Should we routinely assess hypothalamic-pituitary-adrenal axis in pediatric patients with Prader-Willi syndrome?

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.

Adrenal insufficiency in pediatric kidney transplantation recipients.

BACKGROUND: Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. METHODS: This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. RESULTS: Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (ß = -16.3, p < .001), 6-month hospitalization days (ß = -3.3, p = .013), creatinine variability (ß = -2.4, p = .025), and occurrence of acute kidney injury (ß = -70.6, p = .01). CONCLUSION: Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.

Relationships between adrenal insufficiency and cardiovascular outcomes in patients with atrial fibrillation, atrial flutter and paroxysmal supraventricular tachycardia.

BACKGROUND: Patients with Adrenal Insufficiency (AI) face elevated cardiovascular risks, but little remains known about arrhythmia outcomes in this context. METHOD: Analyzing the 2016-2019 Nationwide Inpatient Sample, we identified cases of Atrial Fibrillation, Atrial Flutter, and paroxysmal supraventricular tachycardia (PSVT) with a secondary diagnosis of AI. Mortality was the primary outcome while vasopressors and/or mechanical ventilation use, length of stay (LOS), and total hospitalization charges (THC) constituted secondary outcomes. Multivariate linear and logistic regression models were used to adjust for confounders. RESULTS: Among patients with Atrial Fibrillation, Atrial Flutter, and PSVT (N=1,556,769), 0.2% had AI. AI was associated with higher mortality (adjusted OR [aOR] 2.29, p=0.001), vasopressor and/or mechanical ventilation use (aOR 2.54, p<0.001), THC ($62,347 vs. $41,627, p<0.001) and longer LOS (4.4 vs. 3.2 days, p<0.001) compared to no AI. CONCLUSION: AI was associated with higher adverse outcomes in cases of Atrial Fibrillation, Atrial Flutter, and PSVT.

Frequency of stress dosing and adrenal crisis in paediatric and adult patients with congenital adrenal hyperplasia: a prospective study.

OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents. DESIGN: Prospective, observational study. METHODS: Data on AC and SD were collected via a patient diary. In case of AC, medical records were reviewed and patient interviews conducted. Adherence to sick day rules of the German Society of Endocrinology (DGE) and disease knowledge using the German version of the CAH knowledge assessment questionnaire (CAHKAQ) were assessed. RESULTS: In 187 adult patients, the AC incidence was 8.4 per 100 patient years (py) and 5.1 in 100 py in 38 children. In adults, 195.4 SD episodes per 100 py were recorded, in children 169.7 per 100 py. In children 72.3% and in adults 34.8%, SD was performed according to the recommendations. Children scored higher on the CAHKAQ than adults (18.0 [1.0] vs 16.0 [4.0]; P = .001). In adults, there was a positive correlation of the frequency of SD and the incidence of AC (r = .235, P = .011) and CAHKAQ score (r = .233, P = .014), and between the incidence of AC and CAHKAQ (r = .193, P = .026). CONCLUSION: The AC incidence and frequency of SD in children and adults with CAH are high. In contrast to the paediatric cohort, the majority of SD in adults was not in accordance with the DGE recommendations, underlining the need for structured and repeated education of patients with particular focus on transition.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) After Pediatric Cardiac Surgery.

Although current studies do not support the routine use of corticosteroids after cardiopulmonary bypass in pediatric patients, there is incomplete understanding of the potential hemodynamic contribution of postoperative critical illness-related corticosteroid insufficiency in the intensive care unit. By reviewing the available studies and underlying pathophysiology of these phenomena in critically ill neonates, we can identify a subset of patients that may benefit from optimal diagnosis and treatment of receiving postoperative steroids. A suggested algorithm used at our institution is provided as a guideline for treatment of this high-risk population.

Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study.

CONTEXT: Adrenal crisis (AC) is a life-threatening complication that occurs during follow-up of patients with adrenal insufficiency (AI). No prospective study has thoroughly investigated AC in children with primary and secondary AI. OBJECTIVE: This work aimed to determine the incidence and risk factors for AC in patients with pediatric-onset AI. METHODS: This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at age ≤15 years. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis. RESULTS: The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% CI, 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93; 95% CI, 0.89-0.97) and increased number of infections (RR 1.17; 95% CI, 1.07-1.27) as significant risk factors. Female sex (RR 0.99; 95% CI, 0.53-1.86), primary AI (RR 0.65; 95% CI, 0.30-1.41), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02; 95% CI, 0.96-1.08) was not a significant risk factor. CONCLUSION: A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients.

Insuficiencia suprarrenal relativa en pacientes cirróticos / Adrenal insufficiency in cirrhotic patients

La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

La educación terapéutica en pacientes con insuficiencia adrenal crónica / Therapeutic education of patients with chronic adrenal insufficiency

Las enfermedades adrenales tienen una incidencia y prevalencia no despreciable. Se presentan como situaciones agudas y crónicas. La cronicidad y su desarrollo están relacionados con los comportamientos y estilos de vida, e imponen afrontar exigencias terapéuticas que descansan en las decisiones que la persona asume ante su cuidado. Esta condición crónica puede transitar sin síntomas, y demanda una persona activa y responsable ante su cuidado diario, capaz y formada en los requerimientos de su enfermedad, adiestrada para los ajustes terapéuticos necesarios, y capacitada para actuar ante la presencia de un evento agudo. Los proveedores de salud deben establecer un contrato terapéutico con el enfermo. Este hecho requiere un saber hacer, en el cual el enfoque biosocial, las destrezas en la comunicación y las técnicas de enseñanza/aprendizaje resultan tan necesarias como la actualización clínica. La insuficiencia adrenal aguda puede presentarse de novo, o ser consecuencia del mal manejo de una condición crónica ya conocida. Se citan diversas causas, dentro de las que la omisión inadvertida del fármaco o el desarrollo concomitante de un padecimiento precipitante infeccioso o no, resultan las más frecuentes. Los pacientes con insuficiencia adrenal crónica necesitan estar educados para que sean capaces de desarrollar conocimientos, habilidades y conductas que permitan tomar decisiones acertadas ante posibles descompensaciones(AU)

Adrenal diseases have significant incidence and prevalence; they occur as acute chronic situations. Chronicity and development are both related to behaviours and lifestyles and impose therapeutic demands that lie in the decisions of the person in charge of the patient care. This chronic condition may appear without any symptom and requires an active responsible person for daily care of patients, capable and trained in disease requirements and in necessary therapeutic adjustments, and prepared to act when an acute event occurs. The health care providers should set a therapeutic contract with the patient. This fact requires "know-how" that includes biosocial approach, communicative dexterities and teaching/learning techniques, which are as necessary as the clinical update. The acute adrenal insufficiency may present de novo or results from wrong management of already known chronic condition. There are several causes such as the involuntary omission of medical drug or the concomitant development of a precipitating infective or non-infective illness, which are the most common. The patients suffering chronic adrenal insufficiency need education so that they may be able to acquire new pieces of knowledge, skills and behaviors that allow taking right decisions in the face of possible decompensation(AU)

Presença de hipocortisolismo clínico-laboratorial em pacientes com paracoccidioidomicose / Presence of clinic-laboratorial hypocortisolism in patients with paracoccidoidomycosis

Micoses sistêmicas se associam, com frequência, ao acometimento da glândula supra-renal. A revisao de prontuários de 135 pacientes com diagnóstico de paracoccidioidomicose permitiu estimar uma prevalência clínica da doença de Addison em 5,2 por cento dos casos. O diagnóstico de doença de Addison foi feito com base na sintomatologia clássica de insuficiência supra-renal (fadiga, perda de peso, fraqueza, hipotensao, hiperpigmentaçao) ou na vigência de um quadro de insuficiência supra-renal aguda. A investigaçao da funçao supra-renal, na ausência de manifestaçoes clínicas clássicas da doença, foi realizada em 9 pacientes. Nesses casos, mostrou resultados sugestivos de normalidade em relaçao ao eixo dos glicocorticóides. Chamam a atençao os baixos níveis de tensao arterial detectados, sendo a pressao diastólica inferior a 80 mmHg em 89,2 por cento dos casos, bem como o alto percentual de hiponatremia e hipercalemia, respectivamente 13,3 por cento e 7,4 por cento dos pacientes avaliados. Estes dados indicam a necessidade de investigaçao adequada do ponto de vista mineralocorticóide. Enfatiza-se que a utilizaçao de agentes antimicóticos inibidores da esteroidogênese deve ser cuidadosamente monitorizada, num contexto de possível hipofunçao supra-renal.