Characterization of patients with adrenal insufficiency and frequent adrenal crises

Abstract

Objective: This study aimed to characterize the clinical and biochemical features of patients with primary (PAI) and secondary (SAI) adrenal insufficiency who developed adrenal crises (ACs) and estimate the incidence of ACs in these patients. Design: Retrospective case-control analysis of the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387). Methods: 2694 patients with AI (1054 PAI; 1640 SAI) enrolled in EU-AIR. Patients who developed ≥1 AC were matched 1:3 with patients without ACs for age, sex and AI type. Data were collected at baseline and follow-up (mean±SD: PAI 3.2±1.7 years; SAI 2.9±1.7 years). Results: 148/2694 patients (5.5%; n=84 PAI; n=64 SAI) had an AC during the study: 6.53 (PAI) and 3.17 (SAI) ACs/100 patient-years. Of patients who experienced an AC, 16% (PAI) and 9.4% (SAI) experienced ≥1 AC/year. The incidence of adverse events, infectious intercurrent illnesses and infectious serious adverse events were higher in patients with ACs than without ACs. No differences were observed in BMI, HbA1c, blood pressure and frequencies of diabetes mellitus or hypertension between subgroups (PAI and SAI, with and without ACs). At baseline, PAI patients with AC had higher serum potassium (4.3±0.5 vs 4.2±0.4mmol/L; P=0.03) and lower sodium (138.5±3.4 vs 139.7±2.9mmol/L; P=0.004) than patients without AC. At last observation, SAI patients with AC had higher hydrocortisone doses than patients without AC (11.9±5.1 vs 10.1±2.9mg/m2; P<0.001). Conclusions: These results demonstrate that concomitant diseases and cardiovascular risk factors do not feature in the risk profile of AC; however, patients with AC had a higher incidence of infectious events.

Latent Adrenal Insufficiency: From Concept to Diagnosis

“…Conversely, the latter comorbidities were not shown to be associated with a higher risk of adrenal crises according to the new study by Quinkler et al (38). However, they did have more infections associated with adrenal crisis occurrence, confirming their immunocompromised state and inability to defend against viral infections owing to a natural killer cell dysfunction (23,38). Eight % of annual cases of adrenal crises will need in hospital treatment and admission rates were highest in patients aged more than 60 years old (41).…”

“…Patients at higher risk of adrenal crisis were especially those who have a history of a previous adrenal crisis (threefold increase) (36), but also patients that are female (35), older (40) and have diabetes insipidus (35), type 1 diabetes mellitus (41) and cardiac, neurological or pulmonary comorbidities (35,39). Conversely, the latter comorbidities were not shown to be associated with a higher risk of adrenal crises according to the new study by Quinkler et al (38). However, they did have more infections associated with adrenal crisis occurrence, confirming their immunocompromised state and inability to defend against viral infections owing to a natural killer cell dysfunction (23,38).…”

“…A much lower incidence was reported in Switzerland despite insufficient patient education regarding their disease (37). Recently, an analysis of the biggest cohort described to date, including 2694 patients from the European Adrenal Insufficiency Registry, revealed an adrenal crisis incidence of 6.53/100 patient-years, with more than one episode per year in 16% of patients with PAI (38). In the absence of a universal definition of adrenal crisis, its recognition can prove to be difficult.…”

The ISAQ Score Does Not Predict Adrenal Crisis in Patients with Primary Adrenal Insufficiency

“…The pathophysiology of AC is not yet well understood 5 . In retrospective studies, the incidence of ACs has been reported to be 5.2–17 per 100 patient-years in PAI 6 7 8 9 , 4.9–5.8 in congenital adrenal hyperplasia 10 , and 6.5–8.3 per 100 patient-years in prospective studies for PAI 11 12 with ACs being fatal in 6.3% of cases 11 . The most common precipitating factors for ACs are infectious diseases, particularly gastroenteritis and pneumonia, emotional stress, pain, missed glucocorticoid doses or inadequate glucocorticoid dose increases 7 11 13 14 .…”

Emergency card, emergency medication, and information leaflet for the prevention and treatment of adrenal crisis (Addison crisis): an Austrian consensus document

“…Eine Nebennierenkrise im Erwachsenenalter tritt in etwa bei 5-10 (in einer Studie 24) Patient*innen mit NNI innerhalb von 100 Patient*innenjahren auf und hat vermutlich eine Mortalitätsrate (Sterblichkeitsrate) von etwa 0,5 pro 100 Patient*innenjahren [5,[10][11][12][13][14]. Für das Kindesalter wurden ähnliche Zahlen publiziert [15][16][17][18], wobei rezente Studien bei Kindern marginal niedrigere Inzidenzen mit etwa 3-4 Nebennierenkrisen pro 100 Patient*innenjahren berichtet haben [19][20][21][22].…”