BONE-MINERAL DENSITY AND BONE TURNOVER BEFORE AND AFTER SURGICAL CUREOF CUSHINGS-SYNDROME

We measured bone mineral density (BMD) using dual-energy x-ray absorpt iometry in 20 patients with Gushing's syndrome (CS) (14 pre- and 2 pos tmenopausal women, 4 men) before and in 18 of them also at regular int ervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and; 2-h fasting urine samples for measurement of biochemical paramet ers of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Ma rked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased consid erably in almost all patient s. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatm ent values). In the premenopausal patients, the increase in BMD both i n the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 9.05, r espectively). Serum levels of osteocalcin bone alkaline phosphatase, c arboxyterminal propeptide of type I procollagen, aminoterminal propept ide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 pr emenopausal patients with active GS and a control group of 18 age-matc hed healthy premenopausal women. However, the urinary hydroxyproline/c reatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 us. 16.2 +/- 3.5 mu mol/mmol, P < 0.01). In all 9 premenopausal p atients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SE M, P < 0.0001), indicating a prompt increase of osteoblast activity. A lso serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked tel opeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased Significantly between 0 and 3 months Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome. Bone density does not consistently change in the first 6 months after cure, despite an apparently rapid restoration of osteoblast activity. Thereafter remarkable improvement of bone density can be observed in almost all patients.