Is muscle strength an overlooked parameter in patients affected by mild autonomous cortisol secretion?

Adrenal incidentalomas are an increasing clinical concern and, while most are non-functioning adrenal adenomas (NFAA), a relevant subset is associated with mild autonomous cortisol secretion (MACS), condition linked to various comorbidities, including metabolic and musculoskeletal alterations. However, the association with a reduction in muscle strength and mass is still controversial.

We evaluated the effects of mild cortisol excess on skeletal muscle health, body composition, and quality of life (QoL) in patients with adrenal incidentalomas associated with MACS, compared with those with NFAA and healthy controls. Sixty-two participants were enrolled: 21 with MACS, 21 with NFAA, and 20 healthy controls. Skeletal muscle strength was assessed using handgrip dynamometry, the sit-to-stand test, and the Medical Research Council (MRC) scale. Body composition was analyzed by bioelectrical impedance analysis (BIA), and quality of life was assessed using the EQ-5D and SARC-F questionnaires.

Patients with MACS had a significantly higher prevalence of osteopenia and osteoporosis compared to NFAA and controls (61.9% vs. 28.6% and 25%, respectively; p= 0.03). No significant differences were observed in fat-free mass (FFM), muscle mass (MM), or fat mass (FM) among groups. MACS patients showed significantly reduced MRC scores for biceps and quadriceps compared to controls (p=0.04). Patients with osteoporosis/osteopenia and reduced muscle strength exhibited higher post-dexamethasone suppression test (DST) cortisol concentrations although not significant. Similarly, QoL scores showed a trend toward greater impairment in the MACS group.

It's one of the first studies assessing muscle mass and performance in MACS compared to NFAA and healthy controls. Our results underline the impact of mild hypercortisolism on proximal myopathy, suggesting an under-recognized musculoskeletal impact supporting the clinical relevance of MACS.