Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glococorticoid excess due to adrenal mass

Abstract

Objective: Glucocorticoid excess is widely recognized as one of the most important causes of bone loss. The mechanism of glucocorticoid-induced osteoporosis is presumably multifactorial, and consists of the loss of organic and non-organic compounds. Efforts have been made to develop simple physical methods for the assessment of bone tissue for the screening of subjects at high risk of osteoporosis, without the use of radioactive sources or ionizing radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful method for monitoring patients undergoing glucocorticoid therapy, which is the most common cause of glucocorticoid excess. QUS appears to detect more structural bone changes than the traditional methods and allows assessment of bone density and elasticity, both characteristics influenced by organic and non-organic bone compounds. However, the use of QUS has not yet been extensively investigated in subjects with endogenous cortisol excess. The aim of this study was to evaluate the usefulness and predictive power of QUS in assessing bone loss in subjects with differing degrees of endogenous cortisol excess due to adrenal mass. Design: Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44 years) by subclinical CS, defined as lacking clinical signs of hormone excess despite the presence of at least two abnormalities in hypothalamic-pituitary-adrenal axis function, as assessed by routine endocrine tests. All women included were eumenorrhoic. Methods: QUS measurement of amplitude-dependent speed of sound was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared with bone density assessed on lumbar vertebrae (L1-L4) and femoral neck sites by dual-energy X-ray absorptiometry (DEXA). Results: A strongly significant bone loss was detected by finger QUS measurement when the patients were considered either all together or as two subgroups (P < 0.001, all). The bone density decrease in the fingers was similar to that found at the lumbar spine and femoral neck by the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h urinary free cortisol (UFF) excretion (P < 0.01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS (P < 0.05). Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss (P < 0.05). A positive correlation between the results of the two techniques was found in controls (P < 0.05) but not in patients. The lack of correlation between the two techniques in patients can probably be attributed to the different parameters of bone alteration measured by the techniques. Conclusions: The detection of bone loss in subclinical CS similar to that in overt CS suggests that all subjects with endogenous cortisol excess should be evaluated for bone mass. QUS measurement appears to be a reliable, radiation-free, simple and fast tool for the identification of bone alteration in subjects with endogenous cortisol excess.