Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing's syndrome and in patients with adrenal incidentaloma

Although steroid-induced negative effects on bone and collagen have been well described in corticosteroid-treated patients, few studies have extensively evaluated bone and collagen turnover in patients with endogenous Cushing's syndrome. In this work serum bone-Gla protein (BGP), C-terminal cross-linked telopeptide of type I collagen (ICTP) and N-terminal propeptide of type III procollagen (PIIINP) levels were determined in patients with active (n=12) and preclinical (n= 6) Cushing's syndrome, adrenal incidentalomas (n=35) and in healthy controls (n=28). In patients with overt Cushing's syndrome, serum BGP (0.9 +/- 0.2 ng/ml),ICTP (2.7 +/- 0.2 ng/ml) and PIIINP (1.9 +/- 0.2 ng/ml) levels were significantly lower (P < 0.0001) than in controls (5.5 +/- 0.2, 3.9 +/- 0.2 and 3.2 +/- 0.2 ng/ml respectively). In preclinical Cushing's syndrome, serum BGP (2.5 +/- 0.8 ng/ml), ICTP (2.2 +/- 0.1 ng/ml) and PIIINP (2.2 +/- 0.2 ng/ml) levels were significantly lower than in normal subjects (P < 0.0001, P < 0.0001 and P < 0.02 respectively), being similar to those recorded in overt Cushing's syndrome. In patients with adrenal incidentaloma, serum BGP (4.2 +/- 0.5 ng/ml) and ICTP (2.9 +/- 0.2 ng/ml) levels were significantly lower than those found in controls (P < 0.05 and P < 0.001 respectively), while serum PIIINP levels (3.6 +/- 0.2 ng/ml) did not differ from those of normals. In particular, 9/35 patients with adrenal incidentaloma had markedly depressed BGP levels (<2.0 ng/ml; mean 0.8 +/- 0.1 ng/ml); all patients of this subgroup showed an exaggerated 17-hydroxyprogesterone increase after ACTH administration. In the same patients, serum ICTP (3.0 +/- 0.4 ng/ml) and PIIINP (3.6 +/- 0.2 ng/ml) levels did not differ from those found in the incidentaloma group. In conclusion, our study indicates that bone and collagen turnover are markedly affected in patients with overt and preclinical Cushing's syndrome. Although patients with adrenal incidentaloma do not show any signs or symptoms of overt hypercortisolism, the presence of reduced BGP and ICTP levels might be considered a further index of an 'abnormal' pattern of steroid secretion in some of them. As a consequence, the presence of early alterations in markers of bone turnover might be useful for selecting those patients who need more accurate follow-up of the adrenal mass.