Content area
Full Text
Endocr Pathol (2012) 23:191195 DOI 10.1007/s12022-012-9212-0
ACTH-Secreting Pheochromocytoma with False-Negative ACTH Immunohistochemistry
Maria Francesca Cassarino &
Alberto Giacinto Ambrogio & Luca Pagliardini &
Martina De Martin & Valeria Barresi &
Francesco Cavagnini & Francesca Pecori Giraldi
Published online: 27 May 2012# Springer Science+Business Media, LLC 2012
Introduction
Since 1955, when Roux [1] published the first association between pheochromocytoma and Cushings 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 Cushings syndrome [2, 3] while less than 1 % of pheochromocytomas is accompanied by Cushings syndrome [4]. 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 [5]. As regards hypothalamo pituitaryadrenal axis peptides, both adrenocorticotropin (ACTH) and other proopiomelanocortin (POMC)-derived peptides [6, 7] as well as, occasionally, corticotropin-releasing hormone (CRH) [8] have been demonstrated in
pheochromocytomas associated with ectopic Cushings syndrome.
The diagnosis of ectopic Cushings syndrome is known to be fraught, as the most common cause of ACTH-dependent hypercortisolism, i.e., pituitary Cushings 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 [1012]. The diagnosis of ectopic ACTH-secreting Cushings 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.
Methods
Case Report
A 69-year-old woman was referred for generalized weakness and fatigue, facial plethora, truncal obesity, slight striae rubrae, diffuse ecchimoses, leukocytosis (10.2109/l WBC), severe hypertension, mild hypokalemia, and diabetes mellitus developed over the course of several months. Initial testing revealed ACTH-dependent hypercortisolism [urinary free cortisol, 409.7 g/24 h; normal range, 1080; unsuppressed serum cortisol after 1 mg dexamethasone (28 g/dl); ACTH,43.3 pg/ml; normal range, 850] and moderately elevated urinary catecholamines (epinephrine, 80.5 g/24 h; normal
M. F....