Effect of protracted treatment with rosiglitazone, a PPARgamma agonist, in patients with Cushing's disease.
OBJECTIVE
Cushing's disease, hypercortisolism due to a pituitary ACTH-secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH-secreting pituitary adenomas have yielded variable results.


METHODS
Ten patients with Cushing's disease were treated with 4-16 mg rosiglitazone p.o. daily for 1-8 months (median 3 months) and plasma ACTH and cortisol, urinary free cortisol (UFC), as well as parameters of insulin sensitivity, were recorded. An acute challenge with 8 mg rosiglitazone for 2 days preceded long-term rosiglitazone administration.


RESULTS
The acute challenge with rosiglitazone did not significantly modify plasma ACTH and cortisol levels. During protracted treatment with rosiglitazone, four patients showed a persistent reduction in UFC levels (up to 24% of pretreatment values), achieving normalization in three. In the others, UFC as well as plasma ACTH and cortisol decrements were inscribed within wide, random oscillations indicating that disease activity was substantially unchanged. Insulin sensitivity was ameliorated in most patients, without relation to ACTH or cortisol secretion. Untoward effects, such as weight gain, oedema and worsening of ecchymoses, were reported in several patients.


CONCLUSIONS
Although effective in a subset of patients, protracted rosiglitazone administration did not consistently restrain ACTH and cortisol secretion in patients with Cushing's disease. Further investigations are needed to fully define the therapeutic potential of PPARgamma agonists in this disorder.
Pecori Giraldi
Francesca
F
Chair of Endocrinology, University of Milan, Ospedale San Luca, Istituto Auxologico Italiano, Milan, Italy.
Scaroni
Carla
C
Arvat
Emanuela
E
Martin
Martina
M
Giordano
Roberta
R
Albiger
Nora
N
Leao
Adriana A S
AA
Picu
Andreea
A
Mantero
Franco
F
Cavagnini
Francesco
F
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000188:drug therapy*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D001786:Blood Glucose; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone