THU503 An Unusual Case Of Ectopic ACTH Syndrome Secondary To Non-small Cell Lung Cancer
Authors: Hernandez Natalia , Askar Esraa , Fredrick Jason Regis , Schulman-Rosenbaum Rifka C 
Published: October 2023

Disclosure: N. Hernandez: None. E. Askar: None. J.R. Fredrick: None. R.C. Schulman-Rosenbaum: None.

Background: Cushing syndrome (CS) is a clinical entity characterized by HTN, DM, peripheral edema, hypokalemia, metabolic alkalosis, and myopathy. CS can be clinically classified into Corticotropin-dependent vs Corticotropin-independent processes. Those categorized as corticotropin dependent can further be subclassified into Eutopic CS (i.e. from the pituitary) vs Ectopic CS (i.e. extra-pituitary). The extra-pituitary source of ACTH most often comes from intra-thoracic neoplasms, of which small cell lung cancer (SCLC) is the most prevalent. However, here we present a case of a patient with Ectopic ACHT Syndrome (EAS) due to non-small cell lung cancer. Clinical Case: 87-year-old woman with pmhx of RA and HTN was admitted for 2-week history of constipation and lower abdominal pain. Physical exam was notable for hypertension and tachycardia, along with lower abdominal tenderness. Laboratory results showed WBCs of 32,000 (3,800-10,500), K of 2.7 mmol/L (3.5-5.5 mmol/L) and HCO3 was 38 mmol/L (22-29 mmol/L). CT chest and abdomen showed a left perihilar necrotic mass 6.6 X 6.0cm, with loco-regional lymphadenopathy with destructive osseous lesion on the right pedicle of L1 and metastatic disease to the liver and adrenal glands. Paraneoplastic ACTH production was suspected in the setting of metastatic lung cancer. Serum ACTH level was 105 pg/mL (7.2-63.6 pg/mL). Initial 8AM cortisol was 41 ug/dL (6.8-18.4 ug/dL) and 24 hr urine cortisol was 2327 mcg/24 h (3.5-45 mcg/24 h) which proved the diagnosis of ACTH-dependent hypercortisolemia.

The AM cortisol was 62.3 ug/dL (6.0-18.4 ug/dL) after the 1mg dexamethasone test consistent with hypercortisolemia secondary to ectopic ACTH. IR biopsy of the right axillary LN showed poorly differentiated non-small cell carcinoma with squamous differentiation. The patient was started on chemotherapy, as well as, mifepristone 300 mg daily and ketoconazole 200 TID for hypercortisolism. She was also considered for Metyrapone. However, cortisol levels did not improve despite optimized therapy due to the aggressive nature of the cancer. Later chemotherapy was discontinued and was discharged on hospice with ketoconazole and mifepristone.

Conclusion: EAS is associated with neuroendocrine tumors of which up to 50% are caused by SCLC and rarely with adenocarcinoma. However, our case is novel as the source of ACTH was a lung tumor of squamous cell origin. Treatment strategies for ACTH secreting tumors combine chemotherapy as well as medications that target the hormonal imbalance such as steroidogenesis inhibitors and cortisol receptor blockers. Unfortunately, patients with ACTH producing tumors tend to have low median survival rates which limits our ability as clinicians to determine the effectiveness of such interventions. Given the uniqueness of her case, it would be even harder to predict the type of clinical response obtained from such treatment.

Presentation: Thursday, June 15, 2023