Leucine metabolism in patients with Cushing's syndrome before and after successful treatment

Bowes, S. B.; Benn, Jonathan; Scobie, I N; Umpleby, A. Margot; Lowy, C.; Sönksen, Peter H.

doi:10.1111/j.1365-2265.1993.tb02414.x

Cited by 17 publications

(19 citation statements)

References 38 publications

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“…The estimated duration of cortisol excess correlated negatively with QUS-determined bone density only in subclinical CS patients, who were characterized by longer duration of the disease. These findings are in accordance with previous observations describing the degree of bone loss related to dose and duration of glucocorticoid therapy (1,37). Also a protracted low-dose treatment (37), presumably not associated with clear signs and symptoms of Cushing's syndrome, has been found to decrease BMD.…”

Section: Discussionsupporting

confidence: 82%

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

Tauchmanovà¹,

Rossi²,

Nuzzo³

et al. 2001

European Journal of Endocrinology

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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 , 0X001, 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 , 0X01, both). Finger Z-scores also correlated inversely with the estimated duration of subclinical CS P , 0X05X Concerning disease activity, only UFF was confirmed by multivariate analysis to be an independent factor influencing bone loss P , 0X05X A positive correlation between the results of the two techniques was found in controls P , 0X05 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 endog...

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Section: Discussionsupporting

confidence: 82%

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

Tauchmanovà¹,

Rossi²,

Nuzzo³

et al. 2001

European Journal of Endocrinology

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“…This has been explored in Cushing's syndrome, where protein breakdown and synthesis have been reported to be proportionately reduced (2) or not different from those in normal subjects (44). In both studies the rate of protein oxidation was similar to normal subjects (2,44), an observation that is not consistent with the progressive protein loss that occurs in this condition. Cushing's syndrome is associated with severe perturbations of body composition (3,9,49).…”

mentioning

confidence: 58%

“…Differences in LBM account for 60 -80% of the explained variability of rates of all three indexes of leucine turnover (16,51), and correction of whole body leucine turnover for the size of the LBM is now standard practice. Because LBM is markedly reduced in Cushing's syndrome, failure to correct for it in previous studies (2,44) would have resulted in underestimation of all indexes of leucine metabolism. Had we failed to correct for LBM, we would have come to a similar erroneous conclusion, that L ox is normal in Cushing's syndrome (Table 3).…”

Section: Discussionmentioning

confidence: 99%

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Protein metabolism in glucocorticoid excess: study in Cushing's syndrome and the effect of treatment

Burt¹,

Gibney²

2007

American Journal of Physiology-Endocrinology and Metabolism

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How protein metabolism is perturbed during chronic glucocorticoid excess is poorly understood. The aims were to investigate the impact of chronic glucocorticoid excess and restoration of eucortisolemia in Cushing's syndrome (CS) on whole body protein metabolism. Eighteen subjects with CS and 18 normal subjects (NS) underwent assessment of body composition using DEXA and whole body protein turnover with a 3-h constant infusion of L-[13 C]leucine, allowing calculation of rates of leucine appearance (leucine Ra), leucine oxidation (Lox), and leucine incorporation into protein (LIP). Ten subjects with CS were restudied after restoration of eucortisolemia. Percentage FM was greater (43.9 Ϯ 1.6 vs. 33.8 Ϯ 2.4%, P ϭ 0.002) and LBM lower (52.7 Ϯ 1.6 vs. 62.1 Ϯ 2.3%, P ϭ 0.002) in CS. LBM was significantly correlated (r 2 Ͼ 0.44, P Ͻ 0.005) to leuceine Ra, Lox, and LIP in both groups. After correcting for LBM, leucine Ra (133 Ϯ 5 vs. 116 Ϯ 5 mol/min, P ϭ 0.02) and Lox (29 Ϯ 1 vs. 24 Ϯ 1 mol/min, P ϭ 0.01) were greater in CS. FM significantly correlated (r 2 ϭ 0.23, P Ͻ 0.05) with leucine Ra and LIP, but not Lox in CS. In multiple regression, LBM was an independent determinant of all three indexes of leucine turnover, FM of leucine R a , and LIP and CS of L ox. Following restoration of eucortisolemia, Lox was reduced (⌬Ϫ7.5 Ϯ 2.6 mol/min, P ϭ 0.02) and LIP increased (⌬ϩ15.2 Ϯ 6.2 mol/min, P ϭ 0.04). In summary, whole body protein metabolism in CS is influenced by changes in body composition and glucocorticoid excess per se, which increases protein oxidation. Enhanced protein oxidation is a likely explanation for the reduced protein mass in CS. Successful treatment of CS reduces protein oxidation and increases protein synthesis to prevent ongoing protein loss. whole body leucine turnover; body composition; resting energy expenditure

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“…Urine creatinine excretion is primarily a function of muscle mass, and muscle mass is substantially reduced in Cushing's syndrome as part of the generalized wasting of connective tissue that occurs. For example, decreases in lean body mass of 20% have been documented in Cushing's syndrome (15). Thus, much of the apparent increase in urinary bone resorption markers could be accounted for in this way.…”

Section: Mechanisms Of Glucocorticoid Effects On Bonementioning

confidence: 93%

Glucocorticoid Effects on Bone

Reid

1998

The Journal of Clinical Endocrinology & Metabolism

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Leucine metabolism in patients with Cushing's syndrome before and after successful treatment

Abstract: We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.

Cited by 17 publications

References 38 publications

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

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

Protein metabolism in glucocorticoid excess: study in Cushing's syndrome and the effect of treatment

Glucocorticoid Effects on Bone

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