title: DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS INCREASES CENTRAL BODY FAT ACCUMULATION IN MALES AFFECTED BY DIABETES MELLITUS AND LATE-ONSET HYPOGONADISM.
abstract: OBJECTIVE
  Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH).
  
  
  METHODS
  Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered.
  
  
  RESULTS
  The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 [interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 [interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 [P<.001]; β = 1.156 [P<.001]; β = -7.675 [P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH.
  
  
  CONCLUSIONS
  Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tirabassi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Muscogiuri
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Balercia
mesh_terms: D017668:Age of Onset; D000368:Aged; D050218:Body Fat Distribution; D003480:Cushing Syndrome / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000503:physiopathology*