No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo.
Clin Neuropathol
; 28(6): 430-9, 2009.
Article
en En
| MEDLINE
| ID: mdl-19919817
ABSTRACT
OBJECTIVE:
Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD) and Nelson's syndrome (NS). However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas. First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines. Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo. MATERIALS ANDMETHODS:
Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day). In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days.RESULTS:
Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo. In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls.CONCLUSION:
In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hidrocortisona
/
Hormona Adrenocorticotrópica
/
Tiazolidinedionas
/
Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)
/
PPAR gamma
/
Síndrome de Nelson
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Neuropathol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Alemania