Increased Risk of Vertebral Fractures in Patients With Mild Autonomous Cortisol Secretion

Abstract

Context The risk of vertebral fractures (VFx) in patients with adrenal incidentalomas (AI) and mild autonomous cortisol secretion (MACS) is debated. Objective To evaluate the VFx prevalence and incidence in patients with AI and MACS. Design Cross-sectional and longitudinal study on retrospective data. Setting Four Italian endocrinology units. Patients 444 patients (cross-sectional arm) and 126 patients (longitudinal arm, follow-up 24.9 ± 5.3 months) to evaluate prevalent and incident VFx, respectively, in patients with MACS (MACS-yes) and without MACS (MACS-no). Main outcome measures serum cortisol after 1 mg-dexamethasone test (F-1mgDST), bone mineral density (BMD) by dual-energy x-ray absorptiometry at spine (LS) and femur (FN), and the VFx presence by x-ray. Results Cross-sectional arm: 214 and 230 patients were MACS-yes and MACS-no, respectively, based on F-1mgDST >1.8 µg/dl (50 nmol/L). Patients with MACS had higher VFx prevalence (62.6%) than those without MACS (22.9%, p < 0.001); MACS was associated with prevalent VFx (odds ratio, OR, 5.203, 95%Confidence Interval, 95%CI, 3.361-8.055, p < 0.001; relative risk, RR, 2.07), regardless of age, body mass index (BMI), gender distribution, LS-BMD and presence of type 2 diabetes mellitus (T2D). Longitudinal arm: 66 and 60 were MACS-no and MACS-yes patients, respectively. Patients without MACS showed higher incident VFx (36.4%) than those without MACS (10.0%, p < 0.001); MACS was associated with incident VFx (RR 4.561, 95%CI 1.600-13.003, p = 0.005) regardless of age, LS-BMD, gender distribution, presence of prevalent VFx and T2D. Results were confirmed in women and men when separately evaluated Conclusions Women and men with AI and MACS are at higher risk of VFx.

Prevalence and Incidence of Fractures in Patients With Nonfunctional Adrenal Tumors

“…Previous studies in patients with adrenal tumors have found increased fracture risk in individuals with higher cortisol levels. 11 , 12 , 17 In contrast to the current study, these studies did not exclude individuals with MACS. Moreover, a control group without known adrenal masses is very rare in studies of adrenal tumors.…”

“…Previous studies in patients with adrenal tumors have found increased fracture risk in individuals with higher cortisol levels . In contrast to the current study, these studies did not exclude individuals with MACS.…”

“…However, Li et al had medical records available since 1966 in their examined county, whereas we had only national data using ICD-10 , which was introduced in Sweden in 1997 (ie, an almost 20-year difference, which may explain the prevalence difference). Moreover, our vertebral fracture prevalence rate of 1.5% in patients with NFATs (compared with 0.9% in controls) was also much lower than the 6.4% reported by Li et al but even lower compared with the rates of 22.9% to 24.7% reported by other recent studies . We suspect that this drastic difference in prevalence is due to inclusion of asymptomatic vertebral fractures in the previous studies because all patients with NFATs had their spines evaluated radiologically, whereas our study and the study by Li et al possibly included only symptomatic vertebral fractures.…”

“…Moreover, our vertebral fracture prevalence rate of 1.5% in patients with NFATs (compared with 0.9% in controls) was also much lower than the 6.4% reported by Li et al 13 but even lower compared with the rates of 22.9% to 24.7% reported by other recent studies. 11 , 12 We suspect that this drastic difference in prevalence is due to inclusion of asymptomatic vertebral fractures in the previous studies 11 , 12 because all patients with NFATs had their spines evaluated radiologically, whereas our study and the study by Li et al 13 possibly included only symptomatic vertebral fractures. Moreover, these studies with very high vertebral fracture rates were from tertiary specialized endocrine clinics, likely introducing a selection bias, whereas our study and the study by Li et al 13 were population based, minimizing the risk of selection bias.…”

“… 9 MACS has been reported to be associated with mainly increased cardiometabolic risk, 10 but increased occurrences of fractures have also been found in studies. 11 , 12 Interestingly, in a population-based cohort study conducted in 1 county, patients with NFAT were more likely to have previous fractures when diagnosed with an NFAT and an increased incidence of new fractures during follow-up. 13 However, larger studies are needed.…”