Pathophysiology of osteoporosis (PATHOS Study): role of hidden cortisol excess (HidHyCo) and its predictors in bone fragility, preliminary results

Cristina Eller-Vainicher; Valeria Citterio; Giorgia Grassi; Elisa Cairoli; Romina Mirsepanj; Enrico Buccheri; Alberto Ghielmetti; Sabrina Corbetta; Luigi Gennari; Alfredo Scillitani; Agostino Gaudio; Iacopo Chiodini

doi:10.1530/endoabs.110.P5

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Endocrine Abstracts (2025) 110 P5 | DOI: 10.1530/endoabs.110.P5

ECEESPE2025 Poster Presentations Bone and Mineral Metabolism (112 abstracts)

Pathophysiology of osteoporosis (PATHOS Study): role of hidden cortisol excess (HidHyCo) and its predictors in bone fragility, preliminary results

Cristina Eller-Vainicher ¹ , Valeria Citterio ¹ , Giorgia Grassi ¹ , Elisa Cairoli ² , Romina Mirsepanj ^2,3 , Enrico Buccheri ⁴ , Alberto Ghielmetti ¹ , Sabrina Corbetta ^2,5 , Luigi Gennari ⁶ , Alfredo Scillitani ⁷ , Agostino Gaudio ^4,8 & Iacopo Chiodini ^9,10

Author affiliations

¹Endocrinology Unit, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy; ²Bone Metabolic Diseases and Diabetes Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy; ³Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; ⁴Unit of Internal Medicine, Policlinico “G. Rodolico”, Catania, Italy; ⁵Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; ⁶Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; ⁷Endocrine Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy; ⁸Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; ⁹Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy; ¹⁰Unit of Endocrinology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

JOINT1963

Objective: To assess the prevalence of hidden hypercortisolism (HidHyCo) in a large sample of patients with osteoporosis or osteopenia plus the comorbidities possibly associated with cortisol excess and to evaluate the characteristics predictive of HidHyCo

Methods: From April 2023 to January 2025 we enrolled, in 5 Italian hospitals, 1194 patients without clinically overt hypercortisolism or other secondary causes of osteoporosis. Patients were referred for evaluation of osteoporosis or fragility fractures, or for osteopenia associated with ≧1 of these conditions: hypertension (treated ≧2 drugs or not well controlled, severe-hypertension), diabetes, history of cardiovascular events (CVE).

Measurements: In all patients we collected data regarding history of fragility fractures, diabetes, hypertension and CVE. Bone mineral density was measured with DXA at lumbar spine and femur and the presence of vertebral fractures (mVFx) was evaluated with thoracolumbar X-ray and the Spinal Deformity Index (SDI) was calculated. All patients performed twice: 1 mg overnight dexamethasone suppression test (DST) and, as confirmatory, 2day low-dose DST (2day-ldDST) for HidHyCo diagnosis.

Results: The presence of HidHyCo was detected in 26 out of 1192 patients (2.2%). As for the characteristics predictive of HidHyCo, here we present a preliminary analysis on 318 patients. Within this group, 43 patients (13.5%) showed DST>1.8 mcg/dl, and in 14 (4.4%) HidHyCo was confirmed. Patients with and without HidHyCo showed no difference in prevalence of osteoporosis (75.0 vs 80.8%, P=0.708), CVE (8.3% vs 2.8%, P=0.314), diabetes (8.3% vs 12.7%, P=1.00) and severe-hypertension (25.0% vs 20.6%, P=0.710). Patients with HidHyCo showed a higher prevalence of mVFX or major clinical fractures (MajorFX) (75.0% vs 37.6%, P=0.014) and higher SDI (4.1±6.3 vs 1.2±2.4, P=0.001). In two separated logistic analyses, adjusted for age, osteoporosis, diabetes, severe-hypertension, the presence of a mVFX or MajorFX (odds ratio, 4.5 [CI, 1.14 to 17.37], P=0.031) and SDI (odds ratio, 1.2 [CI, 1.05 to 1.38], P=0.006) were associated with HidHyCo.

Conclusions: HidHyCo may be more common than is generally recognized in patients with bone fragility in whom other secondary causes have been excluded. The presence of mVFX or MajorFX and the SDI are associated with a higher risk of HidHyCo.