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Adrenal responsiveness to high, low and very low ACTH 1-24 doses in obesity
M MacCario1, S Grottoli, L Divito
1Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy.
Objective:
To investigate adrenal activity in visceral obesity in which adrenal hyperactivity has been hypothesized. This could reflect hypothalamus-pituitary alterations leading to slight hyperfunction of the adrenal. Primary adrenal hypersensitivity to ACTH drive in obesity has also been suggested. However, it has also been reported that dehydroepiondrosterone (DHEA) levels in obesity are reduced and it has been hypothesized that this could play a role in the increased cardiovascular risk in obese patients.
Subjects:
We have studied seven obese women with visceral adiposity (OB, age: 33.6+/-3.3 years, BMI: 33.8+/-1.3 kg/m2, WHR: 0.88+/-0.01). The results in OB were compared with those recorded in a group of age-matched normal women (NS, age: 30+/-1.3 years, BMI: 19.9+/-0.4 kg/m2, WHR: 0.76+/-0.02).
Methods:
We have studied the cortisol (F), aldosterone (A) and DHEA responses to ACTH 1-24 administered at low (LD, 0.5 microg/m2) or very low (VLD, 0.125 microg/m2) dose followed by a second challenge with supramaximal dose (HD, 250 microg).
Results:
Basal F, A and DHEA levels in OB were similar to those in NS. The peak F responses to ACTH were dose-related in both groups. At each dose the F peaks in OB (VLD: 495.6+/-43.9 nmol/l, HD: 722.3+/-67.7 nmol/l; LD: 519.2+/-46.0 nmol/l, HD: 729.6+/-44.7 nmol/l) were similar to those in NS (VLD: 556.7+/-45.9 nmol/l, HD: 704.8+/-20.7 nmol/l; LD: 511.8+/-22.8 nmol/l, HD: 726.7+/-26.5 nmol/l). The peak A responses to ACTH were dose-related in both groups. At each dose, the A peaks in OB (VLD: 0.55+/-0.03 pmol/l, HD: 0.79+/-0.09 pmol/l; LD: 0.63+/-0.04 pmol/l, HD: 0.78+/-0.09 pmol/l) were similar to those in NS (VLD: 0.8+/-0.10 pmol/l, HD: 0.86+/-0.09 pmol/l; LD: 0.8+/-0.10 pmol/l, HD: 0.95+/-0.12 pmol/l). The peak DHEA responses to ACTH were dose-related in both groups. At each dose the DHEA peaks in OB (VLD: 58.6+/-13.3 nmol/l, HD: 61.9+/-13.1 nmol/l; LD: 55.18+/-6.4 nmol/l, HD: 72.3+/-9.8 nmol/l) were similar to those in NS (VLD: 54.3+/-8.2 nmol/l, HD: 57.8+/-8.2 nmol/l; LD: 42.2+/-3.7 nmol/l, HD: 56.9+/-4.3 nmol/l).
Conclusions:
This study shows that the cortisol, aldosterone and dehydroepiondrosterone responses to high, low and very low ACTH doses in obese women overlap with those in age-matched lean controls; these findings suggest normal sensitivity of the different zones of the adrenal cortex to ACTH in obesity.