Baseline and CRH-stimulated ACTH and cortisol levels after administration of the peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone, in Cushing's disease.
The ability of acute rosiglitazone administration in influencing ACTH/cortisol secretion in basal conditions and after CRH stimulation was studied in patients with Cushing's disease. Ten patients (8 women and 2 men, aged 18-65 yr) with Cushing's disease were enrolled in the study: 6 of them had previously undergone unsuccessful surgery and 4 were untreated. Plasma ACTH and serum cortisol levels were evaluated at serial time points for 3 h during saline infusion and after the administration of rosiglitazone (8 mg, po) and for 1 h after the injection of CRH (1 microg/kg iv) given alone or 30 min following rosiglitazone administration. The 4 tests were performed in all subjects in randomized order on different days. No significant difference was observed between the pattern of hormone secretion during saline alone and after rosiglitazone, as evaluated by two-way analysis of variance (ANOVA). The integrated areas under the curves (AUCs) were also not significantly different (ACTH: 5683 +/- 1038 vs 6111 +/- 1007 pg/ml/180 min; cortisol: 2333 +/- 267 vs 2902 +/- 486 microg/dl/180 min). In addition, there was no difference for ACTH and cortisol responses to CRH given either alone or after rosiglitazone, when evaluated as peak, increment or AUC; the pattern of the responses analyzed by two-way ANOVA was also similar.


CONCLUSIONS
1) the administration of a single dose of rosiglitazone did not decrease ACTH/cortisol levels or blunt their response after CRH injection; 2) the activation of PPAR-gamma receptors by rosiglitazone seems unable to affect ACTH and cortisol secretion, at least in acute conditions, in patients with ACTH-secreting pituitary adenomas.
Department of Medicine and Pharmacology, Unit of Endocrinology, University of Messina, Messina, Italy. salvatorecannavo@hotmail.com
S
S
Cannavò
B
B
Ambrosi
I
I
Chiodini
T
T
Vigo
A
A
Russo
C
C
Milici
L
L
Barbetta
C
C
Dall'Asta
G
G
Adda
M
M
Arosio
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism; D000328:Adult; D000368:Aged; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism / Q000652:urine; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000378:metabolism; D047748:Pituitary ACTH Hypersecretion / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone