TY - JOUR
T1 - New avenues in the medical treatment of Cushing's disease
T2 - Corticotroph tumor targeted therapy
AU - Fleseriu, Maria
AU - Petersenn, Stephan
N1 - Funding Information:
Conflict of interest Dr. Fleseriu has received consultant fees from Novartis Pharmaceuticals and Ipsen, and is a principal investigator in clinical trials sponsored by Novartis Pharmaceuticals, Corcept Therapeutics, and Ipsen, with research support to OHSU. Dr. Petersenn has received consultant fees from Novartis Pharmaceuticals, Pfizer and Ipsen, and is a principal investigator in clinical trials sponsored by Novartis Pharmaceuticals and Ipsen. Partial financial support (Ken Scholtz and David Wolff) has been provided by Novartis Pharmaceuticals. The authors are solely responsible for all content.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Cabergoline
KW - Cushing's disease
KW - Pasireotide
KW - Pituitary corticotroph adenoma
KW - Retinoic acid
KW - Somatostatin analog
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U2 - 10.1007/s11060-013-1151-1
DO - 10.1007/s11060-013-1151-1
M3 - Article
C2 - 23673515
AN - SCOPUS:84877635563
SN - 0167-594X
VL - 114
SP - 1
EP - 11
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -