SAT321 Ectopic ACTH Cushing's Syndrome Caused By A Large-cell Neuroendocrine Lung Carcinoma Responding To Desmopressin

Disclosure: S. Larose: None. D. Rioux: None. R. Albadine: None. A. Lacroix: None. Background: Ectopic ACTH secretion (EAS) is a less frequent cause of ACTH-dependent Cushing’s syndrome (CS), most often caused by a thoracic neuroendocrine tumor (NET). Large-cell neuroendocrine carcinomas (LCNEC) with EAS are rare and usually present a more severe phenotype of ACTH secretion and hypercortisolism. Clinical Case: We report the case of a 44-yo non-smoking man, who presented clinical and biochemical evidence of ACTH-dependent severe CS complicated by pulmonary emboli. In the context of an initial equivocal pituitary MRI, desmopressin and CRH stimulation tests were performed. Desmopressin produced a 157% increase in ACTH (basal: 59.0 pmol/L to peak: 151.9 pmol/L) and a 25% increase in cortisol from baseline; there was no stimulation of ACTH or cortisol during a CRH test and no suppression with high dose dexamethasone tests. Repeat pituitary MRI identified a 5 mm lesion, but inferior petrosal venous sinus sampling (IPSS) under desmopressin did not identify a central ACTH source. Thorax and abdominal imaging including Indium-111 octreoscan identified a left lung 3 mm micronodule which became more evident when pulmonary emboli resolved. In this context of probable ectopic ACTH secretion, the patient was treated with left inferior lung lobectomy for a suspected NET. Pathological studies confirmed a lung LCNEC with morphologic features of carcinoid tumor and strongly positive ACTH immunohistochemistry (IHC) in the primary lesion and lymph node metastasis. The patient was in CS remission after surgery and adjuvant chemotherapy, but developed a CS recurrence 9.5 years later, with a morning ACTH of 56.9 pmol/L, (N <11.0 pmol/L), a non-suppressed AM cortisol of 633 nmol/L after 1mg of dexamethasone overnight and urinary free cortisol of 1717 nmol/24 hours (N:< 789). Imaging showed signs of recurrence, with a hypermetabolic, 14 x 11 mm left hilar lymph node lesion on a TEP-DOTATATE scan in the left lung, near the surgical suture. An endobronchial ultrasound-guided biopsy confirmed the recurrence of the LCNEC. Surgery was performed and demonstrated again positive ACTH IHC of the lesion. The patient achieved remission of CS with secondary adrenal insufficiency, treated with hydrocortisone. Six months later, there was no response of ACTH or cortisol to a desmopressin test. Conclusion: This is the first report of LCNEC with morphologic feature of carcinoid tumor of the lung with ectopic ACTH secretion stimulated by desmopressin. Long delay prior to metastatic recurrence indicates relatively indolent NET. This case report indicates that response to desmopressin can occur in malignant LCNEC. Combining the desmopressin test with other dynamic tests, sellar MRI, IPSS and thoraco-abdominal functional imaging improves diagnostic accuracy of ectopic ACTH source. Presentation: Saturday, June 17, 2023