Ectopic Cushing's Syndrome

Abstract

images in clinical medicineT h e n e w e ng l a n d j o u r na l o f m e dic i n e n engl j med 365;25 nejm.org december 22, 2011 e46 A 23-year-old man presented with a 1-year history of diabetes mellitus, hypertension, and hypogonadism and a weight gain of 22 kg. Abdominal striae were present on physical examination (Panel A). An endocrine evaluation showed a corticotropin-dependent hypercortisolism: his morning cortisol level after an overnight dexamethasone suppression test was 38 µg per deciliter (1048 nmol per liter) (reference range, <1.8 µg per deciliter [<49.7 nmol per liter]) and his corticotropin level was 287 pg per milliliter (63.2 pmol per liter) (reference range, <46 pg per milliliter [<10.1 pmol per liter]). Endogenous cortisol production could not be suppressed with the administration of high-dose dexamethasone and could not be stimulated with the administration of corticotropin-releasing hormone, a finding that suggested a diagnosis of Cushing's syndrome resulting from the ectopic secretion of corticotropin. Axial computed tomographic images of the chest revealed an anterior mediastinal tumor (Panel B, arrow). The mass was assumed to be a thymic carcinoid tumor and was completely resected. Histologic analysis suggested a tumor with a nested, or zellballen, pattern of growth (Panel C, left inset, hematoxylin and eosin), strong and diffuse positivity for synaptophysin (Panel C, upper-right inset), and S-100 positivity for sustentacular cells (Panel C, bottom-right inset, arrows); there was no histologic evidence of cancer. These findings confirmed a diagnosis of corticotropin-producing mediastinal paraganglioma. Postoperative levels of serum cortisol and corticotropin were low. On follow-up 3 months later, the patient showed nearly complete clinical recovery.

MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

“…They are usually aggressive, poorly differentiated NEC, frequently accompanied by locoregional invasion and metastases (42,43,44,45,46). More rarely, EAS can be due to a thoracomediastinal paraganglioma (52,53,54).…”

“…Pheochromocytoma/paraganglioma: These catecholamine-secreting endocrine tumors are a rare cause of EAS, and are responsible for less than 5% of all reported EAS cases (56,57,58,59). They are mostly unilateral, localized and retroperitoneal (18,51,52,53,54). In rare cases, EAS can be due to a bilateral pheochromocytoma associated with MEN2A (18,51,52,53,54).…”

“…They are mostly unilateral, localized and retroperitoneal (18,51,52,53,54). In rare cases, EAS can be due to a bilateral pheochromocytoma associated with MEN2A (18,51,52,53,54).…”

“…From a diagnostic perspective, it is therefore crucial to assay methoxyamines, in addition to urinary cortisol, in EAS associated with adrenal/ abdominal mass especially in cases of severe hypertension. Pheochromocytomas responsible for EAS also raise specific issues for management of blood pressure (21,54,55,56,57). The potentiation of catecholamines-induced hypertension by cortisol-induced stimulation of the pheno l-eth olami ne-N-methy l-tra nfera se enzyme, which is responsible for the transformation of noradrenaline to adrenaline, has been described in the rare instance of catecholamine and ACTH co-secreting pheochromocytomas (60).…”

Ectopic Cushing’s syndrome due to retroperitoneal ACTH-producing paragangliomas

“…EAS cases due to paraganglioma have been reported in only 10 patients (Table 1). [4][5][6][7][8][9][10][11][12][13] The tumour was located in the mediastinum in four of them, in paranasal sinus in three, and in the retroperitoneum in three patients. Only one patient had malignant tumours located throughout the thorax and abdomen.…”