Paraneoplastic Cushing Syndrome: A Sign of Occult Malignancy

Abstract

SESSION TITLE: Metastatic and Other Primary Lung Tumors SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Cushing Syndrome (CS) results from prolonged hypercortisolism. While often caused by iatrogenic administration of exogenous steroids or Cushing Disease, CS is also rarely caused by secretion of ACTH from ectopic sources, such as malignancies. Though rare - with ectopic ACTH secretion (EAS) accounting for only >15% of endogenous CS cases - diagnosis of CS can lead to earlier discovery of occult malignancy and increase potential for successful treatment. Clinicians therefore need a high degree of suspicion when faced with such presentations. CASE PRESENTATION: 57-yo man with CKD, CAD, HTN, DM and a long smoking history was admitted with respiratory failure due to CAP with dyspnea, weight gain, abdominal distention, and extremity weakness x 1 month. Physical exam showed reduced breath sounds over his right lower lung fields and abdominal obesity, but no Cushingoid appearance. He had marked refractory HTN. Labs showed profound hypokalemia with metabolic alkalosis, hypoxemia, hypercapnia and leukocytosis. CXR showed a right pleural effusion and basilar infiltrate. Elevated serum cortisol and ACTH levels helped diagnose CS. Abdominal CT showed no adrenal mass. Lab tests ruled out pheochromocytoma. A negative dexamethasone suppression test led to suspicion for EAS. CT Chest showed a mass with RML bronchial obstruction, mediastinal LAD and bilateral noncalcified lung nodules concerning for metastatic disease. While pleural fluid analysis showed a transudative effusion and microbiology was negative, cytology showed atypical cells suspicious for malignancy. Biopsy of the RML mass allowed for a unifying diagnosis of small cell carcinoma (SCLC) as the cause of the paraneoplastic CS. Chemotherapy was promptly started. DISCUSSION: Current standard practice for CS diagnostic work-up includes 8 mg dexamethasone suppression and CRH stimulation tests, inferior petrosal sinus sampling (IPPS), and imaging including CT, MRI, octreotide scans and venous sampling. In cases of EAS, the majority did not respond to CRH stimulation or dexamethasone suppression. IPPS was found most likely to identify the disease. Hypercortisol control treatments range from medications such as ketoconazole, metyrapone, or etomidate to surgical bilateral adrenalectomy. The highest rate of cure, up to 65%, came with the surgical removal of the ectopic ACTH-secreting neoplasm though recurrence was a possible complication. While cure in nonsurgical candidates is relatively rare, survival was common except in those cases of paraneoplastic CS caused by aggressive diseases. CONCLUSIONS: Though rare and difficult to recognize, Paraneoplastic CS may be the first sign of malignancy. While the source of EAS may be benign, it can be seen with SCLC, gastrinoma, medullary thyroid cancer and other such aggressive malignancies. Early identification may be lifesaving. Reference #1: Bertherat J. Cushing syndrome due to ectopic ACTH secretion. Orpha Net. 2012; ORPHA:99889 DISCLOSURE: The following authors have nothing to disclose: Vandana Pai, Kim Phung Nguyen, Jennifer Treece, Badar Siddiqui, Lisa McKinney-Smith No Product/Research Disclosure Information