Prerna Dogra, Lana Šambula, Jasmine Saini, Matthew T. Drake, Shobana Athimulam, Stylianos Tsagarakis, Dimitra A. Vassiliadi, Vasiliki Antonopoulou, Rohit Nathani, Catherine D Zhang, Natalia Genere, Urszula Ambroziak, Joanna Hubska, Raul Gregg Garcia, Mohamed Bassiony, Bahaa Salama, Elizabeth J. Atkinson, Vanessa Fell, Darko Kaštelan, Joseph J. Larson, Irina Bancos
OBJECTIVE: Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty. DESIGN: This multicenter cross -sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019-September 2022). All participants completed a bone health questionnaire at enrollment and had dual-energy X-ray absorptiometry bone mineral density assessment within 12-months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use. RESULTS: Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1-8.3) and MACS (OR: 2.2, 95% CI: 1.9-4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1-mg dexamethasone suppression test (post-1mg-DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4-7.5) and NFA (OR: 2.2, 95% CI: 1.1-4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7-26.4) and NFA (OR: 3.8, 95% CI: 1.3-11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6-6.9) and NFA (OR: 1.5, 95% CI: 0.4-6.1), and was not associated with post-1mg-DST cortisol or frailty in the MACS and NFA groups. CONCLUSION: Patients with CS, and those with MACS and post-1mg-DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.