Dopamine receptor expression predicts cabergoline response in persistent somatotroph adenoma.

Background: In a resource limited setting, cabergoline remains an important part of medical management in acromegaly patients with persistent disease after surgery. Response to medical treatment may depend on the receptor expression in these tumors.

Objectives: To study the dopamine receptor subtype2 (D2R) and somatostatin receptor subtypes2&5(SSTR2&SSTR5) expression in somatotropinomas by immunohistochemistry (IHC) and real time/quantitative polymerase chain reaction(qPCR). Also, to determine the relation between density of D2R expression and remission with cabergoline therapy.

Methods: This study included 30 patients with somatotropinomas who underwent surgery and had persistent disease post-surgery treated with cabergoline. Immunostaining and qPCR for D2R, SSTR2&5 were performed on archived GH secreting pituitary adenoma specimens. The clinical, biochemical and radiological details were collected from the hospital electronic medical records.

Results: D2R was the predominantly expressed receptor followed by SSTR2 and SSTR5. The median(range) duration of cabergoline therapy was 20(6-72) months. 23% (7/30) of patients achieved normalization of IGF-I or GH < 1ng/ml (random/post glucose suppression) with cabergoline. Subjects with baseline IGF-1 < 1.5 times the upper limit of normal were more likely to achieve remission with cabergoline. D2R mRNA expression was significantly higher in patients in remission. On ROC curve analysis, a D2R ^ΔΔ CT of 19.2 (19-fold higher expression compared to normal tissue) predicted remission with cabergoline with a sensitivity of 71% and specificity of 74% (AUC 0.745).

Conclusion: D2 receptor profiling of growth hormone secreting pituitary tumors and post-operative IGF-1 level at 3 months are helpful to predict response to medical treatment with cabergoline.