An Endocrine Picture In Disguise: A Progressive Olfactory Neuroblastoma Complicated With Ectopic Cushing Syndrome

Abstract

Objective:To describe a unique case of a 61-yearold patient presenting with ectopic Cushing syndrome as a paraneoplastic phenomenon due to adrenocorticotropic hormone (ACTH)-secreting bone metastasis of an olfactory neuroblastoma (ON).Methods: We report a detailed case, with clinical, biochemical, and imaging findings and compare it with existing literature.Results: A patient with an ON, with subsequent 10-year stable disease after initial craniofacial surgery, presented with paraparesis due to progressively metastasized ON disease located in the thoracic spine. During palliative chemotherapy, severe hypokalemia and muscle weakness developed, being part of paraneoplastic Cushing syndrome. Examination showed that metastatic bone lesions were mostly responsible for the ectopic secretion of ACTH, with just a few ACTH-secreting tumor cells located in the primary tumor. She was treated with a combination of ketoconazole and metyrapone that controlled cortisol levels. However, low potassium levels persisted. Finally, she underwent a bilateral adrenal resection, after which most cushingoid symptoms disappeared. She died 1 month later. Conclusion:Our case shows a growing ON with several bone metastases, which is a rare clinical condition. Moreover, this is the first report that ON is associated with bone metastases that express excessive ACTH secretion (and suggesting dedifferentiation of the primary tumor during chemotherapy treatment). Ectopic Cushing syndrome (with ACTH secreted by ON bone metastasis) can present late in the clinical trajectory. Finally, a bilateral adrenalectomy was needed to correct the life-threatening hypokalemia as part of the ectopic Cushing syndrome. (AACE Clinical Case Rep. 2017;3:e278-e283) Abbreviations: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; IPSS = inferior petrosal sinus smapling; ON = olfactory neuroblastoma

Case-series of paraneoplastic Cushing syndrome in small-cell lung cancer

“…ECS is not responsive to these 2 tests (2, 5). Serum and urinary cortisol levels in ECS are not suppressed to a level <5 µg/dL after 8 mg dexamethasone overnight and after 0.5 mg every 6 h for 8 doses respectively, like our cases.…”

“…Two-thirds of endogenous elevated cortisol is caused by ACTH-secreting pituitary tumors, 15% by primary adrenal glands and 15% by ectopic paraneoplastic Cushing (5). Differentiation between the latter and Cushing disease is often difficult (6).…”

“…It is rare, appearing in 50% of cases in lung cancer (30–46% in carcinoid tumors from which 80% are intrabronchial, 8–20% in SCLC and rarely in adenocarcinoma), in addition to thymic neoplasms in 15%, pancreatic neuroendocrine tumors, medullary thyroid cancers, pheochromocytomas and unidentified tumors in 12–19% of cases as in our last case. Less commonly, it is associated with paragangliomas, breast, kidney, prostate and esophagus cancer (3, 5, 7). …”

A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome with Recurrent Olfactory Neuroblastoma

“…Kadoya et al reported a case study on ectopic ACTH syndrome that occurred at the time of ONB recurrence (10)(11)(12)(13). They proposed several hypotheses as to why Cushing's syndrome developed when it recurred years after its initial onset.…”

“…Olfactory neuroblastomas (ONBs) are rare tumors that arise from the olfactory epithelium. They may occasionally develop paraneoplastic syndrome, and more than 28 cases associated with ectopic ACTH syndrome (8) have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”