The Journal of clinical endocrinology and metabolism · 2013
Medical treatment of Cushing's disease.
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Feelders Richard A, Hofland Leo J
Аннотация
CONTEXT: Cushing's disease (CD) is associated with serious morbidity and, when suboptimally treated, an increased mortality. Although surgery is the first-line treatment modality for CD, hypercortisolism persists or recurs in an important subset of patients. Considering the deleterious effects of uncontrolled CD, there is a clear need for effective medical therapy.
OBJECTIVE: In this review, we discuss molecular targets for medical therapy, efficacy, and side effects of the currently used drugs to treat hypercortisolism and focus on recent developments resulting from translational and clinical studies.
EVIDENCE ACQUISITION: Selection of publications related to the study objective was performed via a PubMed search using relevant keywords and search terms.
MAIN FINDINGS: Medical therapy for CD can be classified into pituitary-directed, adrenal-blocking, and glucocorticoid receptor-antagonizing drugs. Recent studies demonstrate that somatostatin receptor subtype 5 (sst(5)) and dopamine receptor subtype 2 (D(2)) are frequently (co-)expressed by corticotroph adenomas. Pituitary-directed therapy with pasireotide and cabergoline, targeting sst(5) and D(2), respectively, is successful in approximately 25-30% of patients. Adrenal-blocking drugs can be effective by inhibiting steroidogenic enzyme activity. Finally, the glucocorticoid receptor antagonist mifepristone induces clinical and metabolic improvement in the majority of patients. Each drug can have important side effects that may impair long-term treatment. Generally, patients with moderate to severe hypercortisolism need combination therapy to normalize cortisol production.
CONCLUSION: Medical therapy for CD can be targeted at different levels and should be tailored in each individual patient. Future studies should examine the optimal dose and combination of medical treatment modalities for CD.
OBJECTIVE: In this review, we discuss molecular targets for medical therapy, efficacy, and side effects of the currently used drugs to treat hypercortisolism and focus on recent developments resulting from translational and clinical studies.
EVIDENCE ACQUISITION: Selection of publications related to the study objective was performed via a PubMed search using relevant keywords and search terms.
MAIN FINDINGS: Medical therapy for CD can be classified into pituitary-directed, adrenal-blocking, and glucocorticoid receptor-antagonizing drugs. Recent studies demonstrate that somatostatin receptor subtype 5 (sst(5)) and dopamine receptor subtype 2 (D(2)) are frequently (co-)expressed by corticotroph adenomas. Pituitary-directed therapy with pasireotide and cabergoline, targeting sst(5) and D(2), respectively, is successful in approximately 25-30% of patients. Adrenal-blocking drugs can be effective by inhibiting steroidogenic enzyme activity. Finally, the glucocorticoid receptor antagonist mifepristone induces clinical and metabolic improvement in the majority of patients. Each drug can have important side effects that may impair long-term treatment. Generally, patients with moderate to severe hypercortisolism need combination therapy to normalize cortisol production.
CONCLUSION: Medical therapy for CD can be targeted at different levels and should be tailored in each individual patient. Future studies should examine the optimal dose and combination of medical treatment modalities for CD.