Molecular analysis of tumor tissue enabled selection of a successful combined therapy of somatostatin and dopamine agonists in a case of TSH-secreting pituitary adenoma
Ana Quintero1, M Angeles Galvez-Moreno2, Luis Jimenez-Reina3, Antonio J Martinez-Fuentes1, Pedro Benito-Lopez2 & Justo P Castaño1
TSH-secreting pituitary adenomas (thyrotropinomas or TSH-omas) are rare. At diagnosis, TSH-omas are frequently macroadenomas presenting with variable symptoms, and signs of hyperthyroidism. Somatostatin analogs (SSA) are a very efficient treatment to improve clinical signs in patients with TSH-omas, reducing hormone levels (90%) and causing tumor shrinkage (50%).Inhibitory effects of SSA are mediated by a family of five somatostatin receptor subtypes (sst1-5), with sst2 and sst5 being most frequently expressed in most pituitary tumors and enabling treatment with SSA. Dopamine receptor D2 has also been demonstrated in TSH-omas; and its presence and intensity of expression predict the response to treatment with dopamine agonists. Furthermore, a functional interaction between D2 and sst5 receptors has recently been reported suggesting a potential benefit from the combined targeting of these receptors. Here, we report a unique case of a 27-year-old woman diagnosed and managed of a TSH-secreting pituitary macroadenoma by neurosurgical resection. During three months before surgery, patient underwent combined therapy of octreotide LAR (OCT-LAR) and carbimazol. After this period, GH and IGF-1 levels and thyroid function were found to be normal although no changes were detected in magnetic resonance imaging (MRI). After transphenoidal surgery, no intra or immediate post-operative complications were registered. To study the molecular characteristics of this TSH-oma, we evaluated the expression of different genes in a sample of this tumor by conventional PCR. This confirmed expression of somatostatin receptor 2 (sst2) and 5 (sst5) and the dopamine receptor isoforms 2 (DR2 total) and 2 long (DR2L). Taking these results into account, a combined treatment of somatostatin and dopamine analogs was the chosen as therapy. Interestingly, MRIs at 12 and 18 month after combined treatment revealed a substantial reduction of tumor mass in the pituitary gland. Thus, interactive relationship between clinical and molecular studies served to select the most effective combined therapy in this patient. Support: BIO139&CTS1705-J.Andalucia; BFU2007-60180-MEC/FEDER-SPAIN.