MON-512 - Challenging Cases of Cushing'S Syndrome Due to Ectopic ACTH Secretion

Introduction: The estimated annual incidence of ectopic ACTH syndrome (EAS) is 0.56 per one million people. Severe hypercortisolism complicates management and accelerates clinical decline. We present two cases of EAS from different ectopic sites and the challenges in the management of this uncommon condition. Case 1: A 42-year-old male with lung carcinoid tumor with osseous metastasis presented with polydipsia, polyuria, puffiness, and worsening hypertension for 3 weeks. On admission, lab work showed hyperglycemia, severe hypokalemia, and metabolic alkalosis. CT abdomen showed a 16 mm, 90 Hounsfield unit right adrenal nodule enlarged from 1 year ago. Hormonal investigations showed elevated plasma cortisol, 24-hour urinary free cortisol, unsuppressed cortisol following 1 mg dexamethasone suppression test, and a high level of ACTH. Aldosterone and renin levels were normal. Head MRI was negative for a pituitary adenoma. With markedly elevated cortisol and ACTH values, EAS from metastatic carcinoid tumor was suspected. Given the rapid onset of intense hypercortisolism, bilateral adrenalectomy (BA) was performed on hospital day 12. Immunohistochemical staining of the adrenal glands demonstrated metastatic deposits but lacked expression of ACTH. Following hospitalization, he received physiologic hydrocortisone and treatment for lung carcinoid before succumbing to complications of malignancy 1.5 years later. Case 2: A 28-year-old female presented with polyuria, puffiness, and new onset diabetes. Lab work showed hyperglycemia, hypokalemic alkalosis and transaminitis. CT abdomen revealed a 3.7 cm pancreatic mass and multiple liver lesions. Patient was noted to have elevated morning cortisol that remained unsuppressed with 1 mg and 8 mg dexamethasone overnight testing. ACTH level was found to be very high consistent with EAS. Biopsy of the liver lesion confirmed pancreatic neuroendocrine tumor with liver metastasis positive for ACTH staining. Patient was started on ketoconazole to decrease cortisol levels and chemotherapy with FOLFOX. Patient was initially planned for BA if cortisol levels did not improve with ketoconazole. Despite initial improvement, patient developed bacteremia. Patient died on hospital day 43 before further treatment. Autopsy revealed disseminated Aspergillosis.

Discussion: These patients illustrate the rapid progression and grave prognosis of EAS. The main cause of death is either complications of Cushing's syndrome as in case 2 or disease progression as in case 1. EAS is an endocrine emergency, with hypercortisolism requiring BA in almost 50% of cases. If the primary tumor or hypercortisolemia cannot be directly and promptly treated, the experience of these patients infers that expeditious BA will at least control the catabolic symptoms of EAS, allowing more time to treat the primary tumor.

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