BIOCHEMICAL MARKERS OF BONE AND COLLAGEN TURNOVER IN ACROMEGALY OR CUSHINGS-SYNDROME

We evaluated serum bone Gla-protein (osteocalcin, BGP), carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) in 15 patients with active acromegaly (6 M aged 27-54, 4 PMF aged 39-51, 5 MP aged 54-65 years), 12 with active Cushing's syndrome [(CS) 2M of 32 and 42 years; 4PMF aged 25-40; 6 MF aged 50-64)] and controls evenly matched for age, sex and menstrual status. Patients with acromegaly were evaluated before and at regular intervals on octreotide treatment (50-150 mu g t.i.d., s.c.); the duration of the follow-up was 5-49 months (median 28). Endocrine evaluation included measurements of serum GH, IGF-I, BGP, PICP and PIIINP. In a case-control analysis, acromegalic patients showed increased BGP (14.3+/-2.1 vs 8.3+/-2.1 ng/ml p<0.001) and PIIINP concentrations (4.8+/-1.4 vs 3.1+/-0.7 mu g/l, p<0.02). During octreotide treatment we observed a roughly parallel decline of GH, IGF-I and BGP. BGP and log-transformed 24-h mean GH concentrations were positively correlated (r=0.48, p<0.001) as was the case for BGP and IGF-I (r=0.43, p<0.001). Also PIIINP correlated with log-transformed GH (r=0.58, p<0.001) and IGF-I (r=0.35, p<0.05). Serum PICP did not differ in the two groups (152+/-55 vs 120+/-55 mu g/l, NS) and did not correlate either with GH or IGF-I. Patients with CS were evaluated measuring serum and urinary cortisol (UFC), ACTH, BGP, PICP, PIIINP. They showed decreased levels of BGP (3.6+/-2.4 vs 8.2+/-3.2 ng/ml, p<0.01) and PIIINP (2.8+/-0.8 vs 3.7+/-0.8 mu g/l, p<0.05), no differences were evident for PICP (128+/-46 vs 117+/-44 mu g/l). A negative correlation was demonstrated between log-transformed cortisol (24-h mean) and log-transformed BGP (r=-0.60, p<0.05). No correlation was found among the other examined variables. The present study suggests that patients with active acromegaly have increased BGP and PIIINP levels, reflecting enhanced osteoblastic activity and soft tissue overgrowth respectively, that may be reverted by octreotide treatment. In patients with CS reduced levels of BGP and PIIINP and the inverse correlation between BGP and cortisol suggest an inhibitory effect of cortisol on osteoblastic activity and soft tissue collagen synthesis. The apparent discrepancy between BGP and PICP, both major osteoblastic products, could be due to different catabolic pathways.