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Bone Demineralization and Vertebral Fractures in Endogenous Cortisol Excess: Role of Disease Etiology and Gonadal Status

Departments of Molecular and Clinical Endocrinology and Oncology (L.T., R.P., C.D.S., R.R., M.C.D.M., G.L., A.C.) and Biomorphological and Functional Sciences (L.C., M.K., M.S.), Federico II University of Naples, 80131 Naples, Italy

Address all correspondence and requests for reprints to: Annamaria Colao, M.D., Ph.D., Department of Molecular, Clinical Endocrinology, and Oncology, Federico II University of Naples, via Sergia Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it.

Introduction: The effects of endogenous cortisol (F) excess on bone mass and vertebral fractures have still not been thoroughly investigated. The aim of this cross-sectional case-control study was to investigate factors influencing bone demineralization and vertebral fractures in different conditions of F excess, i.e. Cushing’s disease and adrenal and ectopic Cushing’s syndrome.

Materials and Methods: Eighty consecutive patients and 80 controls were prospectively enrolled: 37 patients (21 females) with pituitary ACTH-secreting adenoma, 18 (14 females) with adrenocortical adenoma, 15 (11 females) with adrenal carcinoma of mixed secretion, and 10 (three females) with ectopic ACTH secretion. The groups had similar age. At diagnosis, bone mineral density (BMD) was determined by the dual-energy x-ray absorptiometry technique at the lumbar spine (L1–L4) and femoral neck; vertebral fractures were investigated by standard spinal radiographs.

Results: When comparing the groups with different etiology of F excess, the patients with ectopic ACTH secretion had higher F and lower BMD values than the other subgroups. Morning F (P = 0.03) and testosterone levels (P = 0.04) correlated with lumbar BMD. Vertebral fractures were found in 61 (76%) of the patients, were multiple in 52 (85%) of the cases, and clinically evident in 32 (52%). Only multiple fractures were more frequent in patients with ectopic ACTH hypersecretion (P < 0.05). Lumbar spine BMD was the best predictor of vertebral fractures (P < 0.01). Surprisingly, amenorrheic and eumenorrheic women had similar BMD values and fracture prevalence.

Conclusion: A high prevalence (76%) of vertebral fracture was revealed, regardless of the etiology of the patients’ hypercortisolism. The harmful effects of F excess at the spine were partly counterbalanced by the increased androgen production but were not affected by gonadal status in women.

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