Ectopic ACTH Syndrome Secondary to Small Cell Lung Cancer Presenting as Acute Anxiety

ABSTRACT

Small cell lung cancer (SCLC) can be complicated by paraneoplastic syndromes including ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Early recognition is vital, given the poor prognosis noted in this subset of patients. We present a case of EAS due to SCLC manifesting as acute anxiety. A 55-year-old male former smoker with a history of recently diagnosed diabetes mellitus, hypertension, and anxiety presented with complaints of worsening anxiety and confusion, which he attributed to the ongoing COVID-19 pandemic. Initial examination revealed hypertension (177/73 mmHg), anxious affect, and mild confusion. Laboratory work-up was notable for leukocytosis (18,510/mm3), hypokalemia (2.4 mg/dL, and metabolic alkalosis (33 mmol/L). Workup for refractory hypokalemia revealed elevated serum cortisol level (91.3 μ g/dL), elevated 24-hour urinary free cortisol level of (18,965 mcg/hour), and elevated serum adrenocorticotropic hormone (ACTH) (294 pg/mL). Magnetic resonance imaging (MRI) of the brain was unremarkable. Computed tomography (CT) scan of the chest, abdomen, and pelvis revealed a 2.8 cm soft tissue mass in the right paratracheal mediastinum with lymphadenopathy, suggestive of malignancy. Bronchoscopy with transbronchial needle aspiration of a mediastinal lymph node was performed, and histopathology confirmed the diagnosis of small cell carcinoma complicated by ectopic ACTH production. Progressive hyperactive delirium and metabolic derangements prompted the initiation of ketoconazole and continuous infusion of etomidate in the intensive care setting, with improvement in symptoms. Concurrent radiotherapy and a chemotherapy regimen of etoposide and cisplatin was initiated. Mitotane was administered given persistently elevated cortisol levels. His subsequent hospital course was complicated by septic shock, diverticulitis, and multi-organ failure, leading to a change in goals of care to comfort measures only. EAS is an uncommon manifestation of SCLC, affecting about 1% of these patients. EAS is typified by high levels of cortisol and ACTH which are not suppressed by high dose dexamethasone. EAS portends a poor prognosis in patients with SCLC, with a median survival ranging from 3.5 to 5.5 months. Given the broad range of symptomatology of hypercortisolism, the identification of EAS is often delayed, with a mean duration of 14 months from symptom onset to diagnosis. Our case uniquely presented with the deceptively benign symptom of acute anxiety without any associated respiratory symptoms that would suggest lung cancer. Hormonal suppression was challenging, requiring concurrent use of etomidate, ketoconazole, and mitotane, apart from chemotherapy.