Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?

PURPOSE: Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels. METHODS: Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51-138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation). RESULTS: There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS. CONCLUSIONS: AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.

Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin.

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.