Glucocorticoid excess, either from exogenous exposure or through endogenous overproduction, is a common cause of secondary osteoporosis. We report a 52-year-old woman presenting with multiple stress fractures of the lower extremities, despite various osteoporosis therapeutic regimens. Investigations led to the diagnosis of hypercortisolism of pituitary origin. Pituitary surgery was unsuccessful, justifying a treatment of ketoconazole. In the absence of densitometric osteoporosis, assessment of bone microstructure using high resolution peripheral quantitative computed tomography revealed alterations of both the cortical and trabecular compartments. This case illustrates that hypercortisolism may cause bone fragility in the absence of marked changes in areal bone mineral density.