Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone-secreting adrenal phaeochromocytoma: review of the literature and report of a case

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochromocytoma, causing ectopic Cushing’s syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous, 9-cm mass in the right adrenal gland, and ¹¹¹In-DTPA⁰] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region, corresponding to the adrenal mass. The patient underwent laparoscopic surgery and formalin-fixed and paraffin-embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed. Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma, which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR₁, SSTR_2A, SSTR_2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing’s disease was dependent on CRH overproduction by the pheochromocytoma, in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas, and provide further evidence for functional SSTR subtype SSTR_2a in a subgroup of pheochromocytomas, suggesting that these tumours may represent potential target for octreotide treatment.Key words: phaeochromocytoma, neuroendocrine tumours, somatostatin receptors, octreotide, corticotropin releasing hormone.Phaeochromocytomas are tumours derived from the chromaffin cells of the sympathoadrenal system, generally associated with cathecolamine overproduction. They represent a rare condition, occurring in less than 0.2% of patients with hypertension. The diagnosis of sporadic phaeochromocytoma is based on clinical history and features characterized by the triad episodic headache, sweating, and tachycardia, but an increasing number of these tumours are diagnosed in patients without classical symptoms (Pacak et al., 2001). Ectopic Cushing’s syndrome is one of the possible, albeit unusual, expression of pheochromocytoma. Up to date, there are few reports of pheochromocytomas producing adrenocorticotropic hormone (ACTH) and/or ACTH precursors (O’Brien T et al., 1992; Chen et al., 1995; White et al., 2000), and even more limited is the number of cases in which pheochromocytoma secrete corticotropin releasing hormone (CRH) (Eng et al., 1999; Bayraktar et al., 2006).Similar to other neuroendocrine tumours, pheochromocytomas often express somatostatin receptors (SSTR) (De Herder and Hofland, 2004), but data on the specific SSTRs subtypes expressed within the tumours are thus far sparse and conflicting and the real therapeutic effectiveness of somatostatin analogue in these tumours is still debated (Reubi et al., 1992; Kubota et al., 1994; Epelbaum et al., 1995; Hofland et al., 1999; Mundschenk et al., 2003; Unger et al., 2004; Ueberberg et al., 2005; Unger et al., 2007).