4-HR INFUSION OF HYDROCORTISONE DOES NOT SUPPRESS THE NOCTURNAL INCREASE OF CIRCULATING ACYL- OR DESACYL-GHRELIN IN HEALTHY YOUNG ADULTS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 676-684-Central Regulation of Appetite & Feeding
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-681
Ralf Manfred Nass*1, Jianhua Liu2, Suzan S Pezzoli2, James Patrie3, Leon S Farhy2, Bruce D Gaylinn2 and Michael O Thorner2
1Univ of Virginia Hlth System, Charlottesville, VA, 2University of Virginia Health System, Charlottesville, VA, 3University of Virginia, School of Medicine, Charlottesville, VA
Ghrelin is a 28-amino acid peptide which has orexigenic and GH releasing effects and plays a role in energy homeostasis. Ghrelin is found in the circulation in two main forms: acyl- and desacyl. Both acyl- and desacyl-ghrelin increase at night, when endogenous cortisol levels are low. Exogenously-induced hypercortisolism for 5 days significantly decreased plasma total ghrelin levels (1). Similarly, low circulating total ghrelin levels have been found in patients with endogenous hypercortisolism (1). The aim of this study was to examine whether a short-term (4-hr) infusion of hydrocortisone given at the time of low endogenous cortisol levels (2300h-0300h) suppresses nocturnal acyl- and desacyl-ghrelin levels.

Subjects and Methods: Eight men, age (mean ± SD) 21.5 ± 2.7 yr; BMI 22.4 ± 2.5 kg/m2were studied in a single-blind, placebo-controlled study during two separate overnight admissions on the Clinical Research Unit. They received either a 4-hr (2300h-0300h) infusion of hydrocortisone or saline. The hydrocortisone infusion rate (mg/kg·h ) was 0.3 for the initial 3 min, 0.24 for 9 min, and then 0.135 until the end of the infusion. Plasma acyl- and desacyl-ghrelin levels (using an in-house two-site sandwich assay) and cortisol levels (Immulite 2000) were measured every 10 min for 16 hrs (1700h-0900h). Ghrelin data were analyzed by way of linear mixed models with Bonferroni correction during the sampling period from 2300h to 0300h and 0300 to 0700h. Cortisol data were analyzed using a paired t-test.

Results: Acyl- and desacyl-ghrelin responses (pg/mL) during or after saline vs hydrocortisone infusion were not significantly different from zero. Mean ghrelin differences [upper, lower 95% CI] from 2300h-0300h were: acyl- [0.22 (-7.39, 7.83), p=1.0] and desacyl- [-3.36 (-17.66, 10.95), p=1.0].  From 0300h-0700h they were: acyl- [8.68 (1.07, 16.28), p=0.056] and desacyl-[8.75 (-5.56, 23.05), p=0.4]. Cortisol levels (ug/dL) (mean ± SE) were significantly higher during the hydrocortisone infusion compared to the saline infusion: 2300h-0300h [28.9 ± 0.6 vs 3.5  ± 0.58, p<0.01] and 0300h-0700h [19 ± 0.77 vs 8.4 ± 0.55, p<0.01].

Conclusion: Short-term increase in circulating cortisol levels by exogenous hydrocortisone infusion does not suppress circulating nocturnal acyl- or desacyl-ghrelin levels. Thus, it is unlikely that endogenous cortisol levels are responsible for the diurnal pattern of ghrelin secretion; it is more likely that this reflects circadian control.

1)     Otto B et al., EJE 2004 151: 113-117

Disclosure: MOT: Founder, Ammonett Pharma, Recipient Award, Novo Nordisk, Advisory Group Member, Pfizer, Inc., Advisory Group Member, Ipsen, Advisory Group Member, Chaisma. Nothing to Disclose: RMN, JL, SSP, JP, LSF, BDG

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

Sources of Research Support: 1R01DK076037 (to MOT), R01DK082805 (to LSF)