Fragility Fractures and Cortisol Secretion in Patients With Nonfunctioning Adrenal Incidentalomas

Abstract

Context: The risk of vertebral fractures (VFx) in patients with nonfunctioning adrenal incidentalomas (NFAI) is unknown.

Objective: This work aimed to assess in NFAI patients the prevalence and incidence of VFx and a hormonal marker to identify patients at risk.

Methods: A retrospective, cross-sectional, and longitudinal study of outpatients was conducted. A total of 306 NFAI patients (cross-sectional arm) and 213 controls were evaluated for VFx prevalence; 85 NFAI patients (longitudinal arm, follow-up 30.3 ± 17.5 months) were evaluated for VFx incidence. Main outcome measures included serum cortisol after 1 mg-dexamethasone test (F-1mgDST), lumbar spinal (LS), and femoral neck (FN) bone mineral density (BMD) and VFx presence, by radiograph of the spine.

Results: Cross-sectional arm: prevalent VFx associated with F-1mgDST with a cutoff of 1.2 µg/dL (33 nmol/L, area under the curve 0.620 ± 0.39; P = .002). Compared with controls and NFAI patients with F-1mgDST less than 1.2 µg/dL (group A), NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (group B) showed a higher VFx prevalence (10.8%, 12.6%, and 29.5%, respectively; P < .001 all comparisons), which was associated with F-1mgDST greater than or equal to 1.2 µg/dL (odds ratio 3.02; 95% CI, 1.63-5.58; P < .001) accounting to confounders. Longitudinal arm: the VFx incidence was higher in group B than in group A (19.3% vs 3.6%; P = .05). In group B, all incident VFx occurred in patients without low BMD. The F-1mgDST cutoff for predicting an incident VFx was 1.2 µg/dL, although statistical significance was not reached after adjustment for confounders (P = .061).

Conclusion: In NFAI patients, F-1mgDST levels greater than or equal to 1.2 µg/L (33 nmol/L) are associated with prevalent VFx and may identify patients at risk of incident VFx.

Keywords: adrenal incidentaloma; bone density; cortisol; fractures; osteoporosis.

Figure 1.

Prevalence of vertebral fractures (VFx) at baseline in relation with the presence of low bone mineral density (BMD) in control individuals, in patients from group A and from group B. Low BMD: presence of T-score at any site less than or equal to −2.5 for postmenopausal women and men older than 50 years or of Z-score at any site less than or equal to −2.0 for premenopausal women and men younger than 50 years. Normal BMD: presence of T-score at any site greater than −2.5 for postmenopausal women and men older than 50 years or of Z-score at any site greater than −2.0 for premenopausal women and men younger than 50 years. Controls: age-, sex-, and body mass index–matched control individuals. A, Patients with nonfunctioning adrenal adenoma (NFAI) with cortisol after 1-mg overnight dexamethasone suppression test (F-1mgDST) less than 1.2 µg/dL (33 nmol/L). B, NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (33 nmol/L). VFx prevalence was higher in B patients (29.5%) compared both with controls and A patients (10.8% and 12.6%, respectively; P < .001 for both comparisons). VFx prevalence in the absence of low BMD was higher in B patients (35.6%) compared both with controls and A patients (13.0% and 13.6%, respectively; P < .001 for both comparisons).

Figure 2.

Incidence of vertebral fractures (VFx) in relation with the presence of low bone mineral density (BMD) in a subgroup of patients from group A and from group B. Low BMD: presence of T-score at any site less than or equal to −2.5 for postmenopausal women and men older than 50 or of Z-score at any site less than or equal to −2.0 for premenopausal women and men younger than 50 years. Normal BMD: presence of T-score at any site greater than −2.5 for postmenopausal women and men older than 50 years or of Z-score at any site greater than −2.0 for premenopausal women and men younger than 50 years. A, Patients with nonfunctioning adrenal adenoma (NFAI) with cortisol after 1-mg overnight dexamethasone suppression test (F-1mgDST) less than 1.2 µg/dL (33 nmol/L). B, NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (33 nmol/L). VFx incidence was higher in B patients (19.3%) compared with A patients (3.6%; P < .05). In A patients all incident VFx occurred in the presence of low BMD, while in B patients the 36.4% of incident VFx occurred in the absence of low BMD.

Figure 3.

Comparison between the prevalence and incidence of vertebral fractures (VFx) in patients from group A, group B, and from a historical cohort of patients with mild autonomous cortisol secretion (MACS). Data are from [6].