C51-16 Invasive Aspergillosis in Paraneoplastic Cushing’s Syndrome Secondary to Small Cell Lung Cancer

Abstract Introduction Ectopic ACTH production occurs in 1-6% of small cell lung cancer (SCLC) cases, causing severe hypercortisolism and profound immunosuppression. We present a rare case of invasive pulmonary aspergillosis developing from endogenous immunosuppression in SCLC-associated Cushing’s syndrome early after cancer diagnosis. Case Presentation A 63-year-old woman with diabetes and newly diagnosed SCLC developed rapidly progressive hypoxemic respiratory failure requiring mechanical ventilation two days following initiation of chemotherapy with carboplatin and etoposide. Physical examination revealed cushingoid features and laboratory evaluation confirmed ectopic ACTH production with elevated cortisol (106 µg/dL) and ACTH (1,356 pg/mL). Chest CT revealed worsening middle lobe obstruction and atelectasis consistent with known SCLC, along with bilateral upper lobe nodules (Figure 1A) and new dense left lower lobe consolidation (Figure 1B) demonstrating the classic “halo sign”. Initial blood cultures grew Klebsiella pneumoniae and appropriate antibiotics were initiated. Antifungal therapy with isavuconazonium was started empirically given immunocompromised state and suspicious appearance of chest imaging. Ultimately serum β-D-glucan, serum galactomannan, and tracheal aspirate for Aspergillus fumigatus PCR resulted as positive. Micafungin was added to isavuconazonium for synergistic properties. Metyrapone followed by etomidate infusion was utilized for management of hypercortisolism. Despite aggressive therapy, respiratory failure and shock progressed and the patient’s family decided to withdraw care in line with her advanced directives. Discussion This case highlights the importance of recognizing the invasive potential of aspergillus in patients with solid tumors with ectopic ACTH production. Specifically, in patients with neoplastic lung involvement and hypercortisolemia, any rapidly progressing lung findings should be investigated with bronchoscopy and serum fungal markers. The patient’s cortisol level exceeded 100 µg/dL, equivalent to more than 100 mg of prednisone daily, which impairs cell mediated immunity and consequently created an environment primed for a rapidly progressing invasive fungal infection.Optimal management of concurrent invasive aspergillosis, lung cancer, and hypercortisolemia is complex and no standard approach exists. Simultaneous antifungals, reduction of immunosuppression (hypercortisolemia), glycemic control, management of co-infections are important therapeutic strategies. A strong index of suspicion is critical for early diagnosis and management. Conclusion Invasive aspergillosis can complicate SCLC-associated Cushing’s syndrome early on in disease course. Recognizing the clinical presentation of this complex entity is crucial for early diagnosis. This abstract is funded by: None