Endocrine Abstracts

Dopamine receptors (DR) are expressed in the majority of corticotroph pituitary tumors and the dopamine agonist cabergoline is effective in controlling cortisol hypersecretion in around 50% of patients with Cushing’s disease (CD). In order to characterize the tumors expressing D₂ receptors and the profile of patients which might respond to the treatment with D₂ agonists, the current study has the aim to correlate D₂ receptor expression and the effects of cabergoline with clinical, biochemical and radiological features of patients, as well as to pathological features of tumors removed form the patients. The study included 72 patients with CD. In all patients, D₂ receptor expression, evaluated by immunohistochemistry (IHC), was correlated with the pathological features of the tumors and the characteristics of the patients, whereas in a subgroup of them, D₂ receptor expression, evaluated by RT-PCR, or the cabergoline responsiveness was correlated with the pathological features of the tumors and the characteristics of the patients. The results of the study demonstrated that D₂ receptor expression is significantly associated with the presence of neural pituitary tissue close to the tumors and/or nerve fibers within or surrounding the tumors, presumably expression of the tumor origin from the intermediate zone of the pituitary gland, as well as with the presence of a corticotroph hyperplasia rather than adenoma at the histological evaluation, and PRL staining within the tumor. Moreover, dividing the tumors according to the intensity of D₂ staining, those with the highest D₂ expression, are also associated with lower age, longer disease duration, a relative resistance to dexametasone and CRH and higher prevalence of hyperprolactinemia, together with an undetectable tumor at the imaging techniques and failure at neurosurgery. The initial response to cabergoline treatment was also associated with some of these characteristics of patients and tumors. However, the long-term responsiveness to cabergoline treatment was only associated with the tumor expression of the short isoform of D₂ receptor and/or D₄ receptors. In conclusion, the current study demonstrated that the corticotroph tumors expressing D₂ receptors derive from either the intermediate zone or the anterior lobe of the pituitary gland. Moreover, whereas the tumors originating from the intermediate zone generally express higher number of D₂ receptors and are associated to the best initial responsiveness to cabergoline treatment, those with the expression of short isoform of D₂, deriving from both the intermediate zone and the anterior lobe of the pituitary gland are associated with a long-term responsiveness to cabergoline treatment.