New avenues in the medical treatment of Cushing's disease

Corticotroph tumor targeted therapy

Maria Fleseriu, Stephan Petersenn

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cushing's disease (CD) is a condition of chronic hypercortisolism caused by an adrenocorticotropic hormone-secreting pituitary adenoma. First-line transsphenoidal surgery is not always curative and disease sometimes recurs. Radiotherapy often requires months or years to be effective, and is also not curative in many cases. Consequently, effective medical therapies for patients with CD are needed. Corticotroph adenomas frequently express both dopamine (D2) and somatostatin receptors (predominantly sstr5). Pasireotide, a somatostatin analog with high sstr5 binding affinity, has shown urinary free cortisol (UFC) reductions in most patients with CD in a large phase 3 trial, with UFC normalization and tumor shrinkage in a subset of patients. Adverse events were similar to other somatostatin analogs, with the exception of the degree and severity of hyperglycemia. Two small trials (one prospective and one retrospective) have suggested that cabergoline, a D2 receptor agonist, could be effective in normalizing UFC, but current long-term data results are conflicting. Combination treatment with pasireotide plus cabergoline and the adrenal steroidogenesis inhibitor ketoconazole has been successful, but further investigation in larger trials is necessary. Retinoic acid also showed interesting results in a recent very small prospective study. Glucocorticoid receptor blockade with mifepristone has recently demonstrated improvement in signs and symptoms of Cushing's and glycemic control; however, this modality does not address the etiology of the disease and has inherent adverse events related to its mechanism of action. Pituitary-targeted medical therapies will soon play a more prominent role in treating CD, and may potentially become first-line medical therapy when surgery fails or is contraindicated.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Neuro-Oncology
Volume114
Issue number1
DOIs
StatePublished - Aug 2013

Fingerprint

Corticotrophs
Pituitary ACTH Hypersecretion
Hydrocortisone
Somatostatin
Neoplasms
ACTH-Secreting Pituitary Adenoma
Mifepristone
Somatostatin Receptors
Ketoconazole
Dopamine D2 Receptors
Cushing Syndrome
Glucocorticoid Receptors
Pituitary Neoplasms
Therapeutics
Tretinoin
Hyperglycemia
Adrenocorticotropic Hormone
Signs and Symptoms
Radiotherapy
Prospective Studies

Keywords

  • Cabergoline
  • Cushing's disease
  • Pasireotide
  • Pituitary corticotroph adenoma
  • Retinoic acid
  • Somatostatin analog

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

New avenues in the medical treatment of Cushing's disease : Corticotroph tumor targeted therapy. / Fleseriu, Maria; Petersenn, Stephan.

In: Journal of Neuro-Oncology, Vol. 114, No. 1, 08.2013, p. 1-11.

Research output: Contribution to journalArticle

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