Pulmonary embolism as the presenting symptom and a confounder in ACTH-secreting bronchial carcinoid

Ectopic ACTH-secreting pulmonary neuroendocrine tumors are rare and account for less than 5% of endogenous Cushing’s syndrome cases. We describe an unusual case of metastatic bronchial carcinoid tumor in a young woman presenting with unprovoked pulmonary emboli, which initially prevented the detection of the primary tumor on imaging. The source of ectopic ACTH was ultimately localized by a Gallium-DOTATATE scan, which demonstrated increased tracer uptake in a right middle lobe lung nodule and multiple liver nodules. The histological diagnosis was established based on a core biopsy of a hepatic lesion and the patient was started on a glucocorticoid receptor antagonist and a somatostatin analog. This case illustrates that hypercogulability can further aggravate the diagnostic challenges in ectopic ACTH syndrome. We discuss the literature on the current diagnosis and management strategies for ectopic ACTH syndrome. Learning points: In a young patient with concurrent hypokalemia and uncontrolled hypertension on multiple antihypertensive agents, secondary causes of hypertension should be evaluated. Patients with Cushing’s syndrome can develop an acquired hypercoagulable state leading to spontaneous and postoperative venous thromboembolism. Pulmonary emboli may complicate the imaging of the bronchial carcinoid tumor in ectopic ACTH syndrome. Imaging with Gallium-68 DOTATATE PET/CT scan has the highest sensitivity and specificity in detecting ectopic ACTH-secreting tumors. A combination of various noninvasive biochemical tests can enhance the diagnostic accuracy in differentiating Cushing’s disease from ectopic ACTH syndrome provided they have concordant results. Bilateral inferior petrosal sinus sampling remains the gold standard. Background Endogenous Cushing’s syndrome (CS) has an incidence of two to three cases per one million persons per year and is associated with multisystem morbidity and mortality. This includes myocardial infarction, stroke, fractures, infections, peptic ulcers and venous thromboembolism (1, 2). The most common cause of non-iatrogenic CS is an ACTH-secreting pituitary adenoma, also known as Cushing’s disease (CD), followed by adrenal tumors or hyperplasia (1). Ectopic ACTH syndrome (EAS) from a non-pituitary tumor comprises 10% of CS, of which the most common is small-cell lung cancer (27%) followed by pulmonary carcinoids (21%) (3). Bilateral inferior petrosal sinus sampling (BIPSS) can be used to exclude a pituitary source, but localizing the source of ectopic ACTH is often difficult. Here we describe a case of an ACTH-secreting metastatic bronchial carcinoid in which spontaneous pulmonary emboli at first interfered with the visualization of the lung lesion and further complicated the diagnosis. Because 73% of patients harboring well-differentiated neuroendocrine tumors (NETs) with distant metastasis die within 5 years, timely identification and source localization are important (4).