Endocrine Abstracts

Background: A rare cause of ectopic Cushing’s Syndrome (ECS) is pulmonary neuroendocrine neoplasm (NEN) with a broad spectrum of clinical behavior. At the time of diagnosis, pulmonary NENs may present as occult tumors or well-defined round-to-oval lesions in close relationship to the bronchus. Herein, we describe a NEN that developed ECS three years later in a patient followed up for a solitary pulmonary nodule (SPN).

Case Presentation: A 56-year-old female patient with diabetes, hypertension, and obesity presented with complaints of excessive swelling in the hands, feet and legs for the last two months and fatigue in July 2022. Adrenocorticotropic hormone (ACTH)-dependent CS was detected in the patient whose physical examination suggested CS (moon face, buffalo hump, purple stria, and easy bruising) based on the following test results: ACTH= 149 pg/ml (reference range (RR):0-46), low-dose dexamethasone suppression test (DST)= 34.6 mg/dl, midnight salivary cortisol= 23.03 ng/ml (RR:0.7-2.2), and 24-hour urine cortisol= 1915 mg/day (RR:3-45). The presence of severe hypercortisolemia not suppressed by high-dose DST and deep hypokalemia (K⁺= 2.49 mmol/l (RR:3.5-5.1)) and the absence of any lesion on pituitary MRI suggested an ectopic focus. Subsequently, thin-slice thorax CT showed a 20 mm SPN in the middle lobe of the right lung. The retrospective evaluation revealed that the present SPN was first detected as 15 mm in June 2019. At that time, the nodule had low FDG uptake (SUVmax=2.7) in ¹⁸FDG PET/CT, and a pulmonologist followed up the patient for about 2 years. During this period, the patient did not have any complaints suggesting CS. Moreover, serum cortisol level was suppressed after 1 mg DST which was examined as part of an obesity evaluation in 2019. With this clinical history, Gallium-68 PET/CT was performed but no uptake was detected. Since no extrathoracic focus was detected, a transthoracic fine-needle aspiration biopsy of the nodule was performed. Immunohistochemical studies demonstrated diffuse staining with chromogranin and ACTH and moderate staining with synaptophysin and CD56 in tumoral monomorphic epithelial cells. The absence of mitosis and necrosis in the samples suggested a typical bronchial carcinoid. During the evaluation, hypercortisolemia was controlled with metyrapone at a dose of 1250 mg/day. The multidisciplinary council made the surgical decision.

Conclusions: The present case demonstrates that a stable SPN followed without any clinical findings may actually be a NEN and may lead to ECS over time. Therefore, we believe that rare bronchial carcinoids should be kept in mind during SPN follow-up.