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 (D(2)) and
somatostatin receptor subtype 5 (sst(5)), whereas sst(2) is expressed at lower levels. Activation of these receptors can inhibit
ACTH-release in primary cultured
corticotroph adenomas and compounds that target either sst(5) (
pasireotide, or
SOM230) or D(2) (
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 sst(2)-preferring compound
octreotide is able to reduce
cortisol levels effectively. A recent study showed that D(2) 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.