Chief Cushie ~MaryO~ Posted July 22, 2008 Chief Cushie Report Share Posted July 22, 2008 From Reviews in Endocrine & Metabolic Disorders Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome C. de Bruin, R. A. Feelders, S. W. J. Lamberts and L. J. Hofland(1) Department of Internal Medicine, Erasmus Medical Center, room Ee569 's Gravendijkwal 230, 3015, CE Rotterdam, The Netherlands Received: 11 February 2008 Accepted: 12 June 2008 Published online: 19 July 2008 Abstract Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2 is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5 (pasireotide, or SOM230) or D2 (cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin?dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2 receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases. Keywords Corticotroph adenoma - Cushing's disease - ACTH - Cortisol - Pituitary - Adrenal Disclosure statement: The authors of this manuscript have nothing to disclose. C. de Bruin (Corresponding author)Email: email@example.com R. A. FeeldersEmail: firstname.lastname@example.org S. W. J. LambertsEmail: email@example.com L. J. HoflandEmail: firstname.lastname@example.org Link to comment Share on other sites More sharing options...
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