Vertebral fractures may occur early in the history of Cushing disease associating with male gender and degree of cortisol secretion

Context: Skeletal fragility is a frequent complication of endogenous hypercortisolism; however, the prevalence and determinants of vertebral fractures (VFs) in patients with newly diagnosed, short-duration Cushing disease (CD) remain poorly characterized. Design: In this retrospective study, we evaluated 175 adults with newly diagnosed CD admitted for first transsphenoidal surgery (TSS). VFs were assessed through morphometric analysis of preoperative lateral chest X-rays. Results: VFs were detected in 41 patients (23.4%), with multiple fractures in 56.1% and severe fractures in 31.7%. Median estimated disease duration was 12 months. Patients with VFs had significantly higher serum cortisol concentrations compared with those without VFs (189.5 vs. 171.0 ng/mL; p = 0.034). A cortisol cut-off > 173 ng/mL predicted VFs. In multivariate analysis, male gender and cortisol > 173 ng/mL emerged as independent risk factors for VFs. VFs were also associated with glycemic alterations and hypogonadism. Spine Deformity Index correlated positively with cortisol concentrations. Patients with multiple or severe VFs exhibited higher cortisol concentrations. Notably, postoperative cortisol after overnight 1-mg dexamethasone suppression test remained significantly higher in patients with VFs, and a higher rate of cortisol > 18 ng/mL was observed in those with VFs. Conclusions: VFs may occur in newly diagnosed, short-duration CD and are independently associated with male gender and cortisol excess. A cortisol threshold > 173 ng/mL may help identify patients at increased skeletal risk. Importantly, VFs also appear to prospectively predict disease severity. Early assessment of VFs should be integrated into routine management of CD, as skeletal fragility appears to represent an early relevant marker of disease severity.