A Case of ACTH-Producing Pheochromocytoma Associated with Pregnancy

Abstract

Abstract. Ectopic ACTH syndrome is rarely caused by pheochromocytoma. We report a case of a 28-year-old woman with Cushing's syndrome due to ACTH-producing adrenal pheochromocytoma. She had delivered preterm baby at 32nd week of gestation with 'severe preeclampsia'. After delivery, persistent hypertension accompanied by severe headache led her to being misdiagnosed as Cushing's syndrome due to right adrenal adenoma (normal plasma ACTH level) and cerebral vasculitis of unknown etiology. She was referred to our hospital for surgical treatment. Repeated biochemical studies suggested coexistence of ectopic ACTH syndrome and pheochromocytoma. To reverse her clinical deterioration, right total and left subtotal adrenalectomy was performed with presumptive diagnosis of 1) right adrenal pheochromocytoma causing ectopic ACTH syndrome or 2) coexistence of ACTH-dependent Cushing's syndrome and right adrenal pheochromocytoma. Pathologic examination of right adrenal mass revealed pheochromocytoma which showed strong immunostaining for ACTH. Plasma ACTH and urinary cortisol excretion normalized after surgery, but she succumbed to multiple cerebral infarcts and disseminated intravascular coagulation. Pregnancy and inappropriately low plasma ACTH at initial evaluation might have hampered early diagnosis. To our knowledge, this is the first description of a case with ectopic ACTH syndrome due to pheochromocytoma associated with pregnancy.

Pheochromocytoma Presenting with Multiple Cardiovascular Manifestations

“…Dagartzikas et al [3] described an intracardiac mural thrombus that developed because of cardiomyopathy secondary to excessive catecholamine excretion, which resulted in cardiogenic cerebral embolism. Hill and Schwartzman [4] and Oh et al [5] stated that the cause of cerebral infarction is vasospasm due to excessive catecholamines. Van et al [6] stated that the cause of stroke is cerebral thrombosis because of persistent hypertension.…”

Cushing's Disease and Pregnancy

“…urinary free cortisol level, cortisol circadian rhythm and supression by low dose dexamethasone [20], can be employed also in the pregnant patient but need some adaptation. In fact, urinary free cortisol secretion increases in normal pregnancy and modestly elevated levels (≈100-300 µg/24 h) are compatible with pregnancy per se [17,21]. Conversely, urinary free cortisol levels in pregnant patients with Cushing's syndrome are reportedly extremely high [22,23] and most often do not overlap with levels observed in normal pregnant women.…”

“…This increased prevalence of adrenal Cushing's syndrome in pregnant women hints towards an involvement of "illicit" LH/ßHCG adrenal receptors [16]. A scattering of malignant adrenal tumors and patients with Carney's complex has been reported as well as four patients with ectopic ACTH secretion, three phaeochromocytomas and 1 pancreatic carcinoid [14,15,17].…”

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

“…In particular, intense ACTH release by pheochromocytomas leading to elevation of plasma ACTH concentration represents a rare but classical cause of ectopic ACTH Cushing's syndrome (101,102,103). Therefore, it can be hypothesized that modest intra-adrenal ACTH secretion by chromaffin cells present in corticomedullary mixed tumors or adrenocortical adenoma could exert a paracrine control on the proliferative and secretory activities of adrenocortical cells.…”