Massive weight loss decreases corticosteroid-binding globulin levels and increases free cortisol in healthy obese patients: an adaptive phenomenon?
OBJECTIVE
Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.


METHODS
Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method.


RESULTS
No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P < or = 0.01) as was the decrease in dehydroepiandrosterone (P < or = 0.05 and P < or = 0.01, respectively). CBG decreased from 51.50 +/- 12.76 to 34.33 +/- 7.24 mg/l (P < or = 0.01) following BPD. FCI increased from 11.15 +/- 2.85 to 18.16 +/- 6.82 (P < or = 0.05). Insulin secretion decreased (52.04 +/- 16.71 vs. 30.62 +/- 16.32 nmol/m(-2); P < or = 0.05), and insulin sensitivity increased by 163% (P < or = 0.0001). Serum CBG was related to BMI (r(0) = 0.708; P = 0.0001), body weight (r(0) = 0.643; P = 0.0001), body fat percent (r(0) = 0.462; P = 0.001), C-reactive protein (r(0) = 0.619; P = 0.004), and leptin (r(0) = 0.579; P = 0.007) and negatively to M value (r(0) = -0.603; P = 0.005).


CONCLUSIONS
After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.
Manco
Melania
M
Liver Unit, Bambino Gesù Hospital and Research Institute, Rome, Italy. melaniamanco@tiscali.it
Fernández-Real
José M
JM
Valera-Mora
Maria E
ME
Déchaud
Henri
H
Nanni
Giuseppe
G
Tondolo
Vincenzo
V
Calvani
Menotti
M
Castagneto
Marco
M
Pugeat
Michel
M
Mingrone
Geltrude
G
D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D050110:Bariatric Surgery; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D049628:Body Size; D002784:Cholesterol / Q000097:blood; D003907:Dexamethasone; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D020738:Leptin / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000601:surgery; D012016:Reference Values; D014156:Transcortin / Q000378:metabolism*; D015431:Weight Loss
D001786:Blood Glucose; D020738:Leptin; D019382:Human Growth Hormone; D003907:Dexamethasone; D014156:Transcortin; D002784:Cholesterol; D006854:Hydrocortisone