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Context: Quality of life (QoL) is impaired in patients with chronic adrenal insufficiency (AI) despite standard glucocorticoid (GC) replacement therapy. Current evidence on the determinants of QoL is scarce and limited in very few European countries, and how it relates to AI subtypes remains underexplored. Objective: We conducted the first survey study in patients with AI in the USA to determine the correlations between clinical parameters, adverse outcomes, patient education, socioeconomic factors, and QoL in different subtypes of AI. Design, Setting and Participants: Cross-sectional survey study of 529 patients with AI between 2015 and 2020, at three tertiary centers in the USA. Intervention: Patient-centered questionnaires. Main Outcome Measures: QoL scores using Short-Form 36. Results: Of 529 participants, 223 (42.2%) had primary AI (PAI), 190 (35.9%) had secondary AI (SAI), and 116 (21.9%) had glucocorticoid induced AI (GIAI). Median age at the time of survey was 58 years (IQR: 43–68), 342 (64.8%) were women and 483 (91.3%) were Caucasians. Median duration of AI was 6 years (IQR: 3–14.5), longest in patients with PAI (11 vs 4 years in SAI and GIAI, p=0.0001). Overall, Physical Composite Summary (PCS) score was lower than the Mental Composite Summary (MCS) (38.1±12.9 vs 46.5±11.8). Across the eight dimensions, each individual decade- and sex-adjusted Z-score (using the normative data of USA population) in patients with PAI was significantly higher than that of the other two AI subtypes (all p&amp;lt;0.05), although all Z-scores were still below 0. In multivariate analyses, patients were more likely to report a worse PCS score (&amp;lt;40) if they were women (OR: 3.3, CI 95%: 1.8–6.0), had SAI or GIAI (OR: 2.5, CI 95%: 1.4–4.3), had shorter duration of AI (&amp;lt;6 years) (OR: 2.0, CI 95%: 1.1–3.6), were treated with &amp;gt;25 mg hydrocortisone equivalent daily (OR: 2.3, CI 95%: 1.2–4.6), had more comorbidities related to GC excess (OR: 2.3, CI 95%: 1.3–4.0), reported higher financial burden due to AI (OR: 2.1, CI 95%: 1.3–3.6), and reported difficulties with AI management (OR: 2.5, CI 95%: 1.2–5.2). Women (OR: 2.1, CI 95%: 1.08–4.0), shorter duration of AI (OR: 2.4, CI 95%: 1.4–4.3), higher financial burden due to AI (OR: 2.3, CI 95%: 1.3–4.0), reporting difficulties with AI management (OR: 2.6, CI 95%: 1.4–4.9), and lack of family support during adrenal crisis (OR: 9.1, CI 95%: 2.3–33.3), were predictors of a worse MCS score (&amp;lt;40). Conclusions: Patients with AI have substantially impaired QoL despite GC replacement therapy. Certain determinants of QoL are modifiable and achievable, such as avoiding GC over-replacement, offering detailed hands-on education in self-management, more comprehensive insurance coverage, and more robust domestic support. Our study calls for a multidimensional effort from patients, clinicians, and society to improve QoL in this vulnerable patient population.

Quality of Life and Its Determinants in Patients With Adrenal Insufficiency: A Survey Study From Three Tertiary Centers in the United States