Ectopic Corticotropin-Releasing Hormone (CRH) Syndrome from a Primary Nerve Ectoderm Tumor in the Perineum: A Case Report and Review of the Literature

Context: Cushing's syndrome (CS), which is caused by the isolated production of CRH production instead of ACTH, is extremely rare. Objective: We report the case of a 12-year-old female with a primary nerve ectoderm tumor in the perineum who presented with clinical and biochemical evidence of ACTH-dependent Cushing's syndrome. Case Illustration: After an operation on her vulva, her clinical condition deteriorated rapidly, and her blood cortisol levels were significantly elevated. Pituitary imaging was normal, and cortisol was not suppressed with a high-dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. PET-CT confirmed a tumor in the left perineum and multiple lesions in both lungs. To identify the primary tumor, a biopsy of the mass in the labia was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically, a primitive neuroectodermal tumor (PNET). Results: Immunostaining was negative for ACTH but was strongly positive for CRH. Conclusion: This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis of presentations of ACTHdependent Cushing's syndrome. To the best of our knowledge, there has been no report of ectopic CRH syndrome caused by PNET in children.