SAT291 Remote Monitoring Of Biometric, Proteomic, And Patient-reported Outcomes In Adrenal Insufficiency

Abstract

Abstract Disclosure: A. Ben-Shlomo: None. B. Chazarin: None. G. Gresham: None. M. Choudhary: None. K. Barnhill: None. K. Haptonstall: None. J. Van Eyk: None. Background: Damaged hypothalamic-pituitary adrenal axis may result in adrenal insufficiency (AI) and require hydrocortisone replacement. Currently, there are no biometric or circulating biomarkers to assess hydrocortisone replacement adequacy. Dosing is based on symptomatology, often resulting in over- or undertreatment. Methods: We used remote monitoring precision health solutions to identify AI molecular and biometric biomarkers over 2 weeks. Using remote sampling devices (Mitra Neoteryx), 10-µL dried blood samples were collected weekly for protein analysis by AI subjects before and 5 hours after daily hydrocortisone doses and age- and sex matched adrenal sufficient (AS) subjects at approximately the same times. Continuous physical activity were measured with a wearable biosensor (Fitbit Charge HR) along with remote systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) (Omron Evolv). Self-reported AddiQoL questionnaires were completed twice daily. For biometric endpoints and questionnaires, data are summarized as mean ± SD using two-sided t-tests, where a p value <0.05 is considered statistically significant. For proteomic analysis, median value was calculated, and statistical testing identified differentially expressed proteins (DEPs; FDR<5%). Results: Fifteen AI (6 primary AI [PAI] and 9 secondary AI [SAI] and 15 AS subjects completed the study. AI group mean age was 46.3±15.7 and AS was 41.7±13.2. In both groups, 80% were female. Adherence to home monitoring was 100% in AI subjects and >90% in AS (13/15 assessable for biometrics (activity and BP) and 14/15 for AddiQoL). SBP was lower in PAI (106.2±7.9/68.3±7.6 [n=5]) vs SAI (119.1±15.3/71.1±8.9 [n=8]; p=0.04). Nighttime BP (22:00-05:00) for both PAI (102.3±7.8/68.5±7.9) and SAI (101.2±8.2/63.8±9) were significantly lower than AS (115.5±15.6; p=0.04 and p=0.02, respectively). AI heart rate was lower vs AS at night (61.4±11.6 [n=13] vs 72.5±11.1 [n=11]; p=0.01), especially in PAI (57.7±5 [n=5]; p=0.001). Average daily activity was higher in AS than AI as measured by steps (9010 vs 7787; p=0.02), miles (3.94 vs 3.36; p=0.03) and stair flights (14.19 vs 9.85; p=0.01). On AddiQoL, AI subjects scored lower than AS subjects (126.8±18.1 vs 143.3±14.9, respectively; p<0.0001). Across all dried blood samples, 444 proteins were quantified. Comparing AI vs AS, 78 were identified before morning hydrocortisone dose vs 88 before afternoon dose. Forty-nine DEPs were commonly identified and showed the same regulation trends. Nine DEPs before and 18 DEPs after morning and afternoon dosing, respectively, were identified in AI. None of these DEPs were common, indicating potential blood proteome signature changes in the morning and in the afternoon. Conclusion: Remote monitoring of biometrics and blood proteome in AI is feasible and informative and may identify biomarkers to optimize hydrocortisone replacement therapy. Presentation: Saturday, June 17, 2023