Increased Mortality Risk in Patients With Primary and Secondary Adrenal Insufficiency

Abstract

Context Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. Objective To compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Design Retrospective cohort study. Setting UK general practitioner database (CPRD). Participants 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcome measures All-cause and cause-specific mortality; hospital admission from adrenal crisis. Results With follow-up of 40799 and 406899 person-years for patients and controls respectively, the hazard ratio (HR; [95%CI]) for all-cause mortality was 1.68 [1.58 - 1.77]. HRs were greater in primary (1.83 [1.66 - 2.02]) than in secondary (1.52 [1.40 - 1.64]) disease; (HR; primary versus secondary disease, 1.16 [1.03 - 1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15 - 7.46]). Adrenal crisis contributed to 10% of all deaths. In the first two years following diagnosis, the patients’ mortality rate and hospitalisation from adrenal crisis were higher than in later years. Conclusion Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma

“…Early diagnosis of ICI-induced hypopituitarism is clinically important for the initiation of appropriate treatment and prevention of adrenal crisis, which has a fatal clinical course [ 11 , 12 ]. A latest survey revealed that adrenal crisis accounted for 10% of all deaths of patients with adrenal insufficiency [ 13 ]. Hydrocortisone replacement therapy can be used to treat ICI-induced hypopituitarism, and ICI therapy can be resumed once the patient’s condition stabilizes [ 14 ].…”

Non-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency

“…Even under optimal glucocorticoid replacement, patients affected by PAI show decreased quality of life ( 125 ) and increased mortality, with infections and cardiovascular and respiratory diseases as leading causes of death ( 126 – 128 ). In patients with hypopituitarism, AI has been associated with increased risk of death ( 129 ), and among patients with AI, those with SAI showed higher mortality ( 130 ); however, this result has not been confirmed by a more recent study ( 127 ). Cardiovascular mortality in patients with AI has been reported to be higher in female patients ( 128 ) and is associated with former comorbidities ( 131 ).…”

Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency

“…Main causes of death were cancer, cardiovascular and infectious disease, the latter being possibly driven by inadequate glucocorticoid exposure, especially at times of intercurrent illness ( 10 ). With only limited studies available, the mortality rate from AC is estimated to be 0.3-0.5/100 patient years ( 2 , 5 , 6 , 11 , 12 ).…”