The negative association between total ghrelin levels, body mass and insulin secretion is lost in hypercortisolemic patients with Cushing's disease.
OBJECTIVE
Ghrelin exerts a wide spectrum of endocrine and non-endocrine actions. The stomach is the major source of circulating ghrelin levels that are negatively associated with body mass, insulin and glucose levels. The role of glucocorticoids in ghrelin secretion and action is still unclear.


METHODS
In 8 patients with Cushing's disease (CD, BMI 29.8 +/- 1.6 kg/m(2)), 7 normal (NS) and 6 obese subjects (OB, BMI 32.9 +/- 1.1 kg/m(2)) we studied: a) total ghrelin levels (every 15 min over 3 h) and their correlation with BMI, insulin, glucose, homeostatic model assessment (HOMA) index, ACTH and cortisol levels; b) GH, ACTH, cortisol, insulin and glucose responses to acylated ghrelin administration (1.0 mug/kg i.v. at 0 min).


RESULTS
CD patients had BMI, insulin and glucose levels as well as HOMA index higher than those in NS (P < 0.05) but similar to those in OB. Despite this, total ghrelin levels in CD were similar to those in NS and both were higher (P < 0.05) than those in OB. No correlation was found among total ghrelin and BMI, insulin, glucose, ACTH and cortisol levels in CD patients. The GH responses to ghrelin in CD and OB were similar and both were lower (P < 0.002) than those in NS. In CD ghrelin induced exaggerated ACTH and cortisol responses clearly higher (P < 0.005) than in OB and NS. Ghrelin administration increased glucose in all groups; insulin levels showed slight decrease that was significant (P < 0.05) in OB only.


CONCLUSIONS
Hypercortisolism in humans is associated with impaired ghrelin secretion and action. In fact, total ghrelin secretion in CD is not reduced despite increased BMI, insulin and glucose levels, while the GH and ACTH responses to acylated ghrelin are clearly reduced and enhanced, respectively.
Giordano
Roberta
R
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
Picu
Andrea
A
Pagotto
Uberto
U
De Iasio
Rosaria
R
Bonelli
Lorenza
L
Prodam
Flavia
F
Broglio
Fabio
F
Marafetti
Lisa
L
Pasquali
Renato
R
Maccario
Mauro
M
Ghigo
Ezio
E
Arvat
Emanuela
E
D000215:Acylation; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D054439:Ghrelin; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology; D036361:Peptide Hormones / Q000009:adverse effects / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000150:complications*
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone