Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery.
BACKGROUND
Ghrelin, an endogenous ligand of the GH secretagogue receptor that exerts orexigenic activity, is negatively correlated with body mass index (BMI) and insulin resistance. Conversely, low levels of adiponectin (ApN), a circulating adipocytokine with antidiabetic, antiatherogenic and anti-inflammatory properties, have been found in several insulin-resistant conditions. Although Cushing's syndrome causes several metabolic and hormonal changes leading to insulin resistance and central obesity, few data concerning the impact of glucocorticoid excess on ghrelin and ApN levels are so far available.


METHODS
We evaluated ghrelin and ApN levels in 14 women (age +/- SE 39.5 +/- 3.9 years, BMI +/- SE 25.8 +/- 1.4 kg/m2) with Cushing's disease (CD) at baseline and after successful transsphenoidal surgery (TSS) and in 14 age- and BMI-matched healthy women.


RESULTS
Despite similar levels of fasting glucose, insulin, homeostatic model assessment-estimated insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) values, patients with CD had ghrelin levels lower than controls (117.8 +/- 21.5 vs. 269.6 +/- 51.4 pmol/l, P < 0.01), and ghrelin levels did not correlate with ACTH, cortisol, androgen and GH levels. Patients and controls showed similar ApN levels (11.1 +/- 1.6 vs. 11.5 +/- 2.0 mg/l), which correlated negatively with insulin, HOMA-IR and BMI and positively with QUICKI and high density lipoprotein (HDL)-cholesterol only in controls. At 10.2 +/- 0.7 months after successful TSS, patients showed a significant increase in ghrelin levels compared to pretreatment values (342.5 +/- 25.6 vs. 117.8 +/- 21.5 pmol/l, P < 0.005) along with significant modifications in BMI, insulin, HOMA-IR and HDL-cholesterol and no change in ApN levels. In two patients tested on days 2-4 after TSS, no modification in ghrelin and ApN levels was observed, despite a dramatic reduction in cortisol levels.


CONCLUSIONS
Cortisol excess did not directly affect ghrelin and ApN levels in patients with CD. The observation that ghrelin levels were low during the active phase of CD and increased after recovery suggests that glucocorticoids may influence ghrelin levels indirectly by modulating adiposity and metabolic signals over the long term.
Libè
Rossella
R
Institute of Endocrine Science, University of Milan, Ospedale Maggiore IRCCS, Milan, Italy.
Morpurgo
Paola Silvia
PS
Cappiello
Vincenzo
V
Maffini
Antonia
A
Bondioni
Sara
S
Locatelli
Marco
M
Zavanone
Mario
M
Beck-Peccoz
Paolo
P
Spada
Anna
A
D000208:Acute Disease; D052242:Adiponectin; D000328:Adult; D016022:Case-Control Studies; D003480:Cushing Syndrome / Q000097:blood* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D054439:Ghrelin; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007016:Hypophysectomy; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D036361:Peptide Hormones / Q000097:blood*; D011184:Postoperative Period; D012044:Regression Analysis
D052242:Adiponectin; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D036361:Peptide Hormones; D006854:Hydrocortisone