An in vivo OctreoScan-negative adrenal pheochromocytoma expresses somatostatin receptors and responds to somatostatin analogs treatment in vitro

Abstract

A 52-yr-old woman presented with hypertension, elevated urinary vanillylmandelic acid, metanephrines, normetanephrines, and plasma chromogranin A (CgA), but normal urinary catecholamine levels. Abdominal ultrasonography and subsequent MRI imaging showed a 3 cm nodular lesion of the right adrenal gland also visualized by 123I-meta-iodobenzylguanidine scintigraphy consistent with a pheochromocytoma (PC). Her OctreoScan was negative. The patient underwent right adrenalectomy and histological examination showed a PC. The adrenal medulla tissue was examined for somatostatin (SRIH) receptor subtypes 1 to 5 (SSTR1 to 5) expression by RT-PCR. Cultured tumor cells were treated with either SRIH, Lanreotide (Lan), or an SSTR2 (BIM-23 120) or SSTR5 (BIM-23 206) selective agonist. CgA secretion was measured in the medium by ELISA and catecholamine levels by HPLC after 6h. Cell viability was assessed after 48h. RT-PCR analysis showed that SSTR1, 2, 3 and 4 were expressed. CgA secretion was significantly reduced by SRIH (- 80 %), Lan (- 35 %), and the SSTR2 selective agonist (- 65 %). Norepinephrine secretion was reduced by SRIH (- 66 %), Lan (- 40 %), and BIM-23 120 (- 70 %). Epinephrine and dopamine secretion was also inhibited by treatment with SRIH (- 90 % and - 93 %, respectively) and BIM-23 120 (- 33 % and - 75 %, respectively) but not by Lan. Cell viability was also significantly reduced by SRIH (- 30 %), Lan (- 10 %), and the SSTR2 selective agonist (- 20 %). The SSTR5 selective agonist did not modify either CgA and catecholamine secretion or cell viability. Our data show that SSTRs may be present in a PC although OctreoScan is negative in vivo, and that SRIH and its analogs may reduce both differentiated and proliferative functions in chromaffin cells in vitro. These findings suggest that SRIH analogs with enhanced SSTR2 affinity might be useful in the medical therapy of PC, even when an OctreoScan is negative.