Skeletal involvement in adult patients with endogenous hypercortisolism

Overt endogenous glucocorticoid excess is a well-recognized cause of bone loss and osteoporotic fractures. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut, and affects the secretion of several hormones (in particular gonadotropins and GH), cytokines, and growth factors, influencing bone metabolism. The glucocorticoid excess mainly affects trabecular bone, leading to vertebral fractures in up to 70% of patients. Osteoporotic fractures may be the presenting symptom of an otherwise silent glucocorticoid excess and can precede the diagnosis of hypercortisolism by up to 2 yr. The removal of glucocorticoid excess leads to a recovery of bone mass which is, however, often incomplete and delayed, although it reduces the risk of osteoporotic fractures. Bisphosphonate therapy has been suggested to be useful in maintaining bone mass in these patients. Subclinical hypercortisolism, a condition of impaired hypothalamic-adrenal-axis homeostasis without the classical signs and symptoms of glucocorticoid excess, is a recently defined entity, which has been shown to be associated to increased bone resorption, bone loss, and high prevalence of vertebral fractures regardless of gonadal status. However, data about the effect of this subtle glucocorticoid excess on bone are still scarce and conflicting. Moreover, it is not yet known whether removing the cause of subclinical hypercortisolism leads to a recovery of bone mass and reduces the risk of osteoporotic fractures. Finally, recent data suggest that subclinical hypercortisolism is a common and underrated finding in patients with established osteoporosis. In summary, it is crucial to evaluate the risk of osteoporosis and fractures in patients with glucocorticoid excess; on the other hand, it also seems advisable to screen for glucocorticoid excess patients with osteoporotic fractures without known secondary causes of osteoporosis.