ACTH and cortisol responses to ghrelin and desmopressin in patients with Cushing's disease and adrenal enlargement.
BACKGROUND
Overexpression of ghrelin and vasopressin (V3) receptors demonstrated on corticotrophe adenomas accounts for exaggerated ACTH and cortisol responses to ghrelin and desmopressin (DDAVP) in patients with Cushing's disease (CD).


OBJECTIVE
In this study we have compared ACTH and cortisol responsiveness to DDAVP and ghrelin in CD patients with and without adrenal enlargement.


METHODS
Ghrelin and DDAVP tests were performed in 15 patients with CD (7 with and 8 without signs of adrenal enlargement) with CRH test in 8 patients. In 7 age and sex-matched healthy subjects, ghrelin test was performed. Plasma ACTH and serum cortisol concentrations were measured after ghrelin, DDAVP and CRH. Growth hormone was measured after stimulation with ghrelin.


RESULTS
Significantly higher baseline and peak ACTH and cortisol concentrations after ghrelin were observed in all patients with CD compared to healthy control subjects. Patients with CD and adrenal enlargement had significantly lower baseline and peak ACTH concentrations after stimulation with ghrelin compared to CD patients without adrenal enlargement, while cortisol levels at baseline and after ghrelin administration were similar. Three out of seven patients with CD and adrenal enlargement did not respond to DDAVP while they responded well to CRH and ghrelin.


CONCLUSIONS
Patients with CD and adrenal enlargement pose special diagnostic problems. They may have lower baseline ACTH levels and may not respond to DDAVP while they respond to ghrelin and CRH. Despite increased endogenous cortisol levels in CD, cortisol responses to ghrelin and CRH are preserved in patients with CD and adrenal enlargement.
Institute of Endocrinology, University Clinical Center of Serbia, Belgrade, Serbia.
D
D
Miljic
M
M
Joksimovic
M
M
Doknic
M
M
Ivovic
M
M
Djurovic
S
S
Pekic
M
M
Tancic
I
I
Soldatovic
M
M
Stojanovic
Dj
Dj
Nale
Dj
Dj
Macut
S
S
Damjanovic
V
V
Popovic
D000310:Adrenal Gland Neoplasms / Q000473:pathology; D000311:Adrenal Glands / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin; D005260:Female; D054439:Ghrelin; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000503:physiopathology
D054439:Ghrelin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin; D006854:Hydrocortisone