Inflammatory Markers Link Steroid Profiles to Bone Status in Patients with Autonomous Cortisol Secretion

Autonomous cortisol secretion (ACS) is a common cause of endogenous glucocorticoid-induced osteoporosis. Cortisol excess alone, however, does not fully explain altered bone status, and other steroid hormone changes, including androgen deficiency, may contribute. ACS is also associated with an inflammatory state, which may relate to changes in bone status and steroid profiles.

To investigate whether inflammatory markers are associated with bone status and steroid profiles in ACS and explore their potential mediating role.

Inflammatory markers and bone status were assessed in 106 patients with ACS and 95 with nonfunctioning adrenal tumors (NFAT). Of these, plasma steroid profiles were measured by liquid chromatography-tandem mass spectrometry in 64 patients with ACS and 77 with NFAT. Analyses examining associations between inflammatory markers and bone status or steroid profiles were stratified by sex and menopausal status.

ACS showed a higher systemic immune-inflammation index (SII) and lower prognostic nutritional index (PNI) than NFAT. In premenopausal women with ACS, SII negatively correlated with trabecular bone score (TBS) (r = -0.38), while PNI positively correlated with TBS (r = 0.58). Androsterone-glucuronide (AND-G), an androgen metabolite, was negatively correlated with SII (r = -0.59) and positively with PNI (r = 0.74). SHapley Additive exPlanations and Bayesian kernel machine regression identified AND-G as the strongest contributor to PNI. PNI mediated 59.9% of the association between AND-G and TBS.

Inflammatory markers were associated with deteriorated bone quality, especially in premenopausal women with ACS. Androgen deficiency was associated with inflammation, partially contributing to bone deterioration.