Fat distribution in obese women is associated with subtle alterations of the hypothalamic-pituitary-adrenal axis activity and sensitivity to glucocorticoids
M. Duclos et al., Fat distribution in obese women is associated with subtle alterations of the hypothalamic-pituitary-adrenal axis activity and sensitivity to glucocorticoids, CLIN ENDOCR, 55(4), 2001, pp. 447-454
Objectives: Obesity with abdominal body fat distribution (A-BFD) and hypoth
alamic-pituitary-adrenal (HPA) axis activity are somehow linked, but the ex
act interactions still need clarification. Obese subjects display normal ci
rculating plasma cortisol concentrations with normal circadian rhythms. How
ever, when the HPA axis is pharmacologically challenged, body fat distribut
ion matters and then A-BFD obese women differ from those with subcutaneous
body fat distribution (P-BFD). We hypothesized that lower dose provocative
and suppressive tests than those used to diagnose hypercortisolism of tumou
r origin or adrenal insufficiency would shed some light on the characterist
ics of the HPA axis activity in relation with body fat distribution.
Patients and Methods: Fifty premenopausal obese women were grouped accordin
g to their body fat mass distribution. Their plasma cortisol responses to (
i) two low doses of dexamethasone (0.25 and 0.5 mg) with (ii) low dose of t
he ACTH analogue tetracosactrin (1 mug) were assessed. Salivary cortisol wa
s also determined during the ACTH test.
Results A-BFD differed from P-BFD women in terms of HPA axis responsiveness
. They had comparatively: (i) increased nocturnal cortisol excretion (9.38
+/- 2.2 vs. 6.82 +/- 0.91 nmol/mu mol creatinine, A-BFD vs. P-BFD, respecti
vely, P = 0.03); (ii) increased salivary cortisol response to ACTH stimulat
ion (1 mug) [salivary cortisol peak: 33.4 (14.1-129) vs. 28.5 (13.2-42.8) n
mol/l; salivary AUC: 825 (235-44738) vs. 537 (69-1420) nmol/min/l; A-BFD vs
. P-BFD, P = 0.04 for both]; and (iii) increased pituitary sensitivity to d
examethasone testing [postdexamethasone (0.25 mg) plasma cortisol levels: 1
63 (26-472) vs. 318 (26-652) nmol/l and postdexamethasone (0.5 mg) plasma c
ortisol levels: 26 (26-79) vs. 33 (26-402) nmol/l; A-BFD vs. P-BFD, P = 0.0
1 for both].
Conclusions: These data demonstrate differences in the HPA axis activity an
d sensitivity to glucocorticoids between obese women differing in their bod
y fat distribution, with both enhanced negative and positive feedback in th
ose with abdominal obesity. Several mechanisms may explain these difference
s: central vs. peripheral hypotheses. Thus, abdominal obesity does not appe
ar to be linked solely to one pathophysiological hypothesis.