ACTH-secreting pheochromocytoma with false-negative ACTH immunohistochemistry

Since 1955, when Roux published the first association between pheochromocytoma and Cushing’s syndrome, we have come to appreciate the unique features of this unusual clinical entity. Pheochromocytoma represents a rare cause of hypercortisolism, accounting for less than 5 % of ectopic Cushing’s syndrome while less than 1 % of pheochromocytomas is accompanied by Cushing’s syndrome. Pheochromocytomas are known to be heterogeneous, both functionally and clinically, a likely consequence of their ability to synthesize and secrete peptides in addition to catecholamine, such as vasoactive intestinal polypeptide, somatostatin, and calcitonin. As regards hypothalamo– pituitary–adrenal axis peptides, both adrenocorticotropin (ACTH) and other proopiomelanocortin (POMC)-derived peptides [6, 7] as well as, occasionally, corticotropinreleasing hormone (CRH) [8] have been demonstrated in pheochromocytomas associated with ectopic Cushing’s syndrome. The diagnosis of ectopic Cushing’s syndrome is known to be fraught, as the most common cause of ACTHdependent hypercortisolism, i.e., pituitary Cushing’s disease, must first be excluded. This is accomplished by extensive diagnostic procedures, such as stimulation with CRH, suppression with high dose dexamethasone and inferior petrosal sinus sampling [9]. Imaging does not play a pivotal role in the diagnostic work-up as both pituitary and ectopic ACTH-secreting pituitary tumors may prove elusive and, conversely, false-positive imaging may lead to erroneous tumor localization [10–12]. The diagnosis of ectopic ACTH-secreting Cushing’s syndrome is therefore confirmed by remission of hypercortisolism after removal of the causative lesion and positive ACTH immunostaining in surgical specimens. We here present a thought-provoking ACTH-secreting pheochromocytoma with negative immunostaining for ACTH