Ectopic Cushing Syndrome Secondary to Corticotropin-secreting Wilms Tumor: A Rare Paraneoplastic Phenomenon

Ectopic Cushing syndrome (ECS) is an exceptionally rare cause of endogenous hypercortisolism in children, accounting for less than 1% of pediatric Cushing syndrome (CS) cases. We report a rare case of ECS in an 8-year-old girl secondary to an adrenocorticotrophic hormone (ACTH)-secreting Wilms tumor. She exhibited classical features of hypercortisolism, including rapid weight gain, hypertension, hyperpigmentation, easy bruisability, and a palpable abdominal mass. Laboratory evaluation revealed markedly elevated serum cortisol and ACTH levels, with absent cortisol suppression following low- and high-dose dexamethasone suppression tests, suggestive of ectopic ACTH secretion. Pituitary and thoracic imaging were unremarkable. Contrast-enhanced abdominal computed tomography identified a large left renal mass. She underwent left radical nephrectomy with perioperative hydrocortisone supplementation. Postoperatively, she showed rapid clinical improvement with a significant decline in ACTH levels. Histopathology confirmed a stage III triphasic Wilms tumor with favorable histology. Although initial ACTH immunostaining was negative, repeat staining demonstrated focal ACTH positivity, suggesting tumor heterogeneity. She was subsequently treated with chemotherapy and radiotherapy. Persistently low cortisol levels postsurgery indicated hypothalamic-pituitary-adrenal axis suppression, requiring continued glucocorticoid replacement. This case underlines the importance of considering ectopic ACTH-producing tumors in pediatric Cushing syndrome and highlights the diagnostic complexities associated with focal hormone expression.