Screening for Reversible Osteoporosis: Is Cortisol a Culprit?

In this issue, Chiodini and colleagues (1) measured the prevalence of subclinical hypercortisolism in 219 consecutive patients 44 to 72 years of age with suspected idiopathic osteoporosis. These individuals had no known secondary cause of osteoporosis, had not received drugs known to influence bone or cortisol, and had no apparent signs or symptoms of cortisol excess (including moon facies, red striae, skin atrophy, or buffalo hump). The investigators screened each patient for hypercortisolism with a 1-mg dexamethasone suppression test and required an abnormal response to the 2-mg, 2-day dexamethasone test, in addition to abnormal urine cortisol levels and midnight cortisol values to establish the diagnosis. Overall, 3.3% of the patients had abnormal responses to these tests. Because the patients did not have clinically recognized hypercortisolism, the authors used the term subclinical hypercortisolism to describe the disorder. The study suggests that hypercortisolism may contribute to few cases of osteoporosis, at least in a restricted subpopulation that is older and has experienced fractures. This editorial addresses several questions raised by this unexpectedly high rate of hypercortisolism.

First, are these results believable, given the rarity of the Cushing syndrome? The 3.3% prevalence of subclinical hypercortisolism in patients with suspected idiopathic osteoporosis is surprisingly high. Clinically apparent Cushing syndrome is rare, being diagnosed in 0.7 to 2.4 per 1 million persons annually (2). As a result, until recently, clinically inapparent hypercortisolism has not been considered as an important—and potentially reversible—cause of disorders associated with hypercortisolism. However, studies of patients with diabetes, hypertension, and hirsutism showed a prevalence of the Cushing syndrome of 2% to 4%, 1%, and 0.25%, respectively. In light of these relatively high prevalences and the findings reported by Chiodini and colleagues, it seems reasonable to screen patients with these disorders for hypercortisolism and perhaps even investigate the prevalence of pathogenic …