Pituitary

, Volume 7, Issue 4, pp 265–269 | Cite as

PPAR-γ in Cushing's Disease

Article
First Online:

Abstract

The majority of pituitary tumors that cause Cushing's disease are small (<1 cm diameter), and most disease morbidity is due to the effects of elevated, non-suppressible, ACTH levels that these tumors secrete. Tumor-derived ACTH leads to adrenal-derived steroid hypersecretion and results in many disabling and sometimes life-threatening symptoms including abnormal fat deposition, skin thinning, psychological disturbances, hypertension, diabetes, osteoporosis and muscle weakness. Cushing's disease is associated with high morbidity and ultimately mortality. In experienced specialized centers, 70% of corticotroph microadenomas can be successfully resected by transsphenoidal pituitary surgery. However, surgical “cure” rates for larger ACTH-secreting pituitary tumors are achieved in only 30% of cases, and recent reports highlight a significant recurrence rate after longer term follow-up even in smaller tumors. Post-surgical persistence of ACTH hypersecretion may require pituitary-directed radiation, but this treatment may take some time to be effective, and like extensive surgical pituitary tumor resection, ultimately leads to partial- or total hypopituitarism in ∼80% of cases. Although hypercortisolism may be completely resolved by adrenalectomy, this procedure does not suppress, and may act as a stimulus to pituitary tumor growth, and is associated with other co-morbidity. Although some currently available drug-based treatments for Cushing's disease effectively control hypercortisolism, their drawback has been that they do not impact on pituitary tumor growth. Recent studies have identified the potential utility of peroxisome-proliferator activating receptor-gamma (PPAR-γ) novel ligands in in vitro, and in vivo Cushing's disease models, and have paved the way for early clinical studies to develop novel therapeutic approaches in Cushing's disease.

Keywords

Pituitary Tumor Hypopituitarism Pituitary Surgery Psychological Disturbance Early Clinical Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Division of Endocrinology, Cedars-Sinai Research Medical CenterDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Division of EndocrinologyCedars-Sinai Medical CenterLos Angeles

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