Obesity is associated with lower basal state cortisol, and diminished cortisol response to the low dose ACTH: time to depart from the obesity/pseudo-Cushing myth

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 690-701-Obesity Pathophysiology
Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-697
Yael Sofer*1, Etty Osher2, Yonit Marcus3, Yona Greenman1, Galina Shenkerman4, Yaffa Moshe5, Sigal Shaklai6, Mariana Yaron5, Rona Limor7, Karen Michele Tordjman2 and Naftali Stern1
1Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel, 2Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 3Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel,, 4Tel Aviv Sourasky Medcl Ctr, Tel Aviv, Israel, 5Tel Aviv-Sourasky Medical Center, 6Sourasky Medical Center - Ichilo, Tel-Aviv, Israel, 7Tel Aviv Sourasky Med Ctr, Tel Aviv-Yafo, Israel
Background: Obesity can resemble Cushing's syndrome not only with respect to some clinical and biochemical features such as visceral adiposity, hypertension and metabolic abnormalities but also in terms of increased urinary excretion of cortisol and cortisol metabolites. This has subsequently led to some confusion regarding activity level of the hypothalamic-pituitary axis in obesity. Here we re-examined this question using several tools developed after the evolution of the concept of "pseudo-Cushing in obesity", namely, the measurement of serum free cortisol, salivary cortisol and the dynamic changes of these measures in response to the low dose 1ug ACTH test.

 Goals: To characterize the relationship between basal and dynamic cortisol response to an intravenous bolus dose of 1 ug ACTH in obesity.

Methods:  Total, free and salivary cortisol were tested at the basal state and after a standard challenge with 1 ug ACTH in 22 healthy obese subjects (mean BMI= 42) and 17 healthy lean controls (mean BMI=22).

Results: Mean (+/-SD) basal state total cortisol was significantly lower in obese than in lean subjects (11.7+/-3.6 vs. 15.5+/- 4.4 ug/dl, p=0.006) as were also basal state serum free cortisol (0.53+/-0.24 vs 0.76+/-0.36 ug/dl, p=0.004) and basal statesalivary cortisol (0.23+/-0.10 vs. 0.56+/-0.66 ug/dl, p=0.004). Additionally, baseline total cortisol was inversely related to BMI (r= -0.45; p<0.05), to waist circumference (r= -0.49; p<0.05) and to systolic blood pressure (r= -0.39; p<0.05). Upon challenge with 1ug ACTH, total cortisol response as assessed by either repeated measure ANOVA (p=0.019) or area under the response curve ((P=0.028) was also lower in obese than in lean subjects. Concordant with these findings peak post-1ug ACTH salivary cortisol was lower in the obese relative to the lean subjects (1.14 +/- 0.10 vs. 1.65+/- 0.66 ug/dl, p<0.05)

Conclusion: Basal state as well as peak stimulated cortisol and integrated post-1ug ACTH-stimulated total serum cortisol levels, while within the test-defined normal range, were significantly lower in obese subjects. Obesity is not associated with higher basal cortisol or ACTH-stimulated cortisol reserve and indeed is linked to diminished circulating cortisol which is negatively related to body mass index and waist circumference. In fact, increased serum or salivary cortisol is atypical for obesity and should not be viewed as probable "pseudo-Cushing syndrome".

Nothing to Disclose: YS, EO, YM, YG, GS, YM, SS, MY, RL, KMT, NS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm