PROJECT SUMMARY/ABSTRACT
Mild autonomous cortisol secretion (MACS) is diagnosed in up to 50% of patients with adrenal adenomas1,
affecting 1-2% of adult population. MACS is diagnosed based on abnormal cortisol following dexamethasone
suppression; however, 24h urine cortisol concentrations are usually normal. As we recently showed in the work
sponsored by the current NIDDK K23 award, patients with MACS demonstrate higher incidence of fractures
and report more falls and symptoms of muscle weakness. In our preliminary data we show that when assessed
by a comprehensive multi-steroid panel, patients with MACS demonstrate a unique steroid signature that is
similar to aging adults without adrenal adenomas. We further found that patients with MACS demonstrate
lower cognition and increased frailty and increased senescence biomarkers.
Our overall objective of this project is to understand the link between the abnormal steroid signature and
cognitive function, overall frailty, and biomarkers of cellular senescence. In Aim 1, the domains and the extent
of cognitive impairment will be characterized in patients with MACS, and the association of cognitive function to
accelerated adrenal aging, as measured by the steroid metabolome will be determined. In Aim 2, the
association of cognitive impairment with frailty, advanced glycation products, and biomarkers of senescence
will be determined.
The proposed research will take advantage of the current structure and detailed characterization of subjects
enrolled as part of the K23 NIDDK award as well as another ongoing prospective study of patients with overt
hypercortisolism. The exceptional resources and institutional support at Mayo Clinic, outstanding multi-
disciplinary mentorship and collaborative team, will allow advancement in understanding the steroid signature
associated with cognitive decline that may serve as a diagnostic and prognostic biomarker of cognitive
impairment and frailty.