A rare case of ectopic ACTH syndrome originating from malignant renal paraganglioma

Abstract

SUMMARYEctopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of a non-pituitary ACTH-secreting tumor leading to Cushing's syndrome. Only a few cases have been reported previously as causing ectopic ACTH related to paraganglioma. Herein, we present a case of Cushing's syndrome, in who was proved to be attributable to an ACTHsecreting renal malignant paraganglioma. A 40-year-old woman presented with a five-month history of newly diagnosed hypertension and diabetes, weakness, hyperpigmentation, oligomenorrhea, hirsutism, and acneiform lesions. She showed cushingoid features, including moon face, facial hirsutism, facial and truncal acne, hyperpigmentation, and severe muscle weakness of the limbs. She did not have other findings such as striae, supraclavicular fat accumulation, and buffalo hump. Laboratory examination showed the presence of hypopotasemia, hyperglycemia, hyperthyroidism, and leukocytosis. The serum levels of ACTH, cortisol, and urine-free cortisol were markedly elevated. Results of an overnight 2-mg dexamethasone suppression test included a basal serum cortisol of 61.1 mcg/dL (normal range: 4.6-22.8 mcg/dL) and a cortisol value of 46.1 mcg/dL after dexamethasone administration. There was no suppression found after 2-day 8-mg dexamethasone administration. Magnetic resonance imaging (MRI) of the pituitary gland indicated two microadenomas. An abdominal MRI scan revealed horseshoe kidney, bilateral adrenal hyperplasia, and masses with dimensions of 35 x 31 mm in the left kidney. Inferior petrosal sinus sampling showed no evidence of a central-to-peripheral gradient of ACTH. A positron emission tomography/computed tomography scan showed intense increased activity in the lower pole of the left kidney. Left adrenalectomy and left partial nephrectomy were performed. The resected tumor was diagnosed as the ACTH-secreting paraganglioma in the pathological examination, which was confirmed by immunohistochemical studies with chromogranin A, synaptophysin, and ACTH. Only a few cases of paragangliomas as a cause of ectopic ACTH syndrome have been reported. To our knowledge, this is the first case of renal paraganglioma resulting in Cushing's syndrome due to ectopic ACTH hypersecretion. Arch Endocrinol Metab. 2017;61(3):291-5.

Malignant Pheochromocytomas/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature

“…A total of 150 cases (Table 3) with ectopic secretion from PCs/PGLs have been reported (data presented in Table 3). ACTH secretion accounted for 33% of all cases (n = 49), whereas CRH, VIP, vasopressin, PTH, renin, aldosterone, insulin or somatostatin, GHRH, and neuropeptide Y secretion have also been described [16,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,…”

“…It is probable that ectopic secretion of bioactive compounds from these tumors is often overloooked or clinical manifestations are masked by the hypersecretion of catecholamines. The most frequent ectopically-secreted hormone is ACTH, mostly reported in benign PCs [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Ectopic secretion of hormones or peptides from malignant PCs/PGLs has been reported even more scarcely.…”

“…Ectopic secretion of hormones or peptides from malignant PCs/PGLs has been reported even more scarcely. In particular, only four cases of metastatic PCs/PGLs with biochemically or immunohistochemically confirmed ectopic secretion of hormones or peptides have been described in the English literature so far [25,30,75,80]. In two other cases of malignant PCs/PGLs, ectopic secretion has been suspected but not confirmed biologically or immunohistochemically [97,98].…”

Case Report: An Unusual Case of Ectopic ACTH Syndrome Caused by Mediastinal Paraganglioma

“…Paraganglioma originates from widely distributed specific neural crest chromaffin cells and is relatively rare in clinical practice. Paraganglioma could occur in the kidney ( 7 ), paranasal sinuses ( 8 ), and pulmonary ( 9 , 10 ) and cervical ( 11 ) sites, while the mediastinum is an uncommon site of occurrence. According to the reference, the total incidence of pheochromocytomas and paragangliomas is only about 3 per million ( 12 ).…”

Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization

“…Наиболее часто причиной АКТГ-ЭС являются НЭО, локализующиеся в органах грудной клетки [2], несколько реже -в поджелудочной железе [3] и надпочечниках [4]. Исключительно редко (<1% случаев) НЭО, секретирующие АКТГ, можно встретить в желудочно-кишечном тракте [5], яичниках [6], предстательной железе [7], почках [8], при медуллярном раке щитовидной железы (МРЩЖ) [9]. Несмотря на современные методы диагностики, в 10-30% случаев первичный опухолевый очаг остается неустановленным [10].…”