Overt hypercortisolism causes reduction in bone mass and density. The effects of subclinical Cushing’s syndrome (SCS) on bone markers and structure are still debated. We therefore studied 56 patients with adrenal incidentaloma: group A=35 (20 F 15 M, age 43–79, mean 64.6±1.5; BMI 29.9±0.9 kg/m2) without evidence of hypercortisolism, and group B=21 (10 F 11 M, age 51–76, mean 63.4±1.9, BMI 28.0±1.2 kg/m2) with SCS (i.e. with 2 or more alterations in biochemical tests of HPA axis). All patients underwent evaluation of HPA axis (plasma ACTH, plasma cortisol at 8 and 24, 24 h UFC, Nugent test), bone markers (serum BGP and urinary DPD), lumbar spine DEXA and bone ultrasonography of the phalanx. Group B showed lower values compared to group A of DEXA BMD, T-score, Z-score (P<0.05), and bone transmission time (BTT) (P<0.05), an ultrasonographic parameter who reflects bone structure. No significant differences in bone markers were detected in the two groups. We found significant inverse correlations between midnight serum cortisol and indicators of bone density, such as AD-SoS, UBPI (P<0.05) and DEXA T-score (P <0.01). A direct correlation between midnight serum cortisol and urinary DPD (P<0.01) was found. BTT correlated directly with BGP and inversely with urinary DPD (P<0.0001). There was also a significant direct correlation between BTT and DEXA BMD (P<0.001). Taken together, these data indicate that bone structure is compromised in SCS patients. Moreover, our results suggest that ultrasonographic densitometry is a useful tool in the assessment of bone alterations occurring in SCS. Midnight serum cortisol correlates with parameters of bone structure, providing a highly sensitive marker, that could be used to identify patients with higher risk for osteoporosis
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