A Rare Case of Ectopic Cushing’S Syndrome Caused by Renal Neuroendocrine Tumor Publisher



Sehatpour F ; Panahi N ; Ramezanibinabaj M ; Yahyazadeh SR ; Sefidbakht S ; Tavangar SM ; Manafifarid R ; Soltani A ; Radmard AR ; Mirtaher FS ; Pejman Sani M ; Sajjadijazi SM
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Introduction: Ectopic Cushing’s syndrome (ECS), a paraneoplastic syndrome resulting from tumors secreting adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), often presents with severe hypercortisolism and rapid clinical deterioration. Identifying and surgically removing the ectopic source is crucial. We present a rare case of ECS originating from a neuroendocrine tumor of the kidney. Case presentation: A 36-year-old woman presented with generalized edema, muscle weakness, severe acne, hypertension, hyperglycemia, hypokalemia, and metabolic alkalosis, along with elevated ACTH and cortisol levels. The patient’s condition was managed with ketoconazole, potassium supplementation, insulin, and antihypertensive medications while awaiting localization of the ACTH source. Dynamic pituitary magnetic resonance imaging (MRI) and chest computed tomography (CT) scans were unremarkable. An abdominal CT scan revealed bilateral adrenal cortical hyperplasia and a lesion in the left kidney, but a Gallium-68 DOTATATE positron emission tomography–computed tomography (PET/CT) scan did not show any avid lesions. En-bloc resection of the left kidney mass was performed. Immunohistochemical (IHC) staining confirmed a well-differentiated neuroendocrine tumor that was negative for ACTH but positive for cytokeratin, chromogranin, synaptophysin, insulinoma-associated protein 1 (INSM1), and paired-box gene 8 (Pax8). Postoperatively, the patient received hydrocortisone to prevent adrenal insufficiency, which was gradually tapered off. The serum levels of cortisol and ACTH returned to normal values. Hypokalemia, metabolic alkalosis, hypertension, and hyperglycemia resolved, and her general condition improved significantly. Discussion: Renal neuroendocrine tumors causing Cushing’s syndrome are exceedingly rare. This case represents a unique instance of an ACTH-negative renal neuroendocrine tumor potentially secreting CRH that caused ECS. This case highlights the importance of considering renal tumors in the differential diagnosis of ECS. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.