Ectopic Cushing syndrome in metastatic castration‑resistant prostate cancer: A case report and review of literature

Abstract

Cushing's syndrome (CS), as a result of ectopic adrenocorticotropic hormone (ACTH) production, constitutes a common paraneoplastic manifestation of various malignancies, with the most common being small cell lung carcinoma. In the literature, fewer than fifty cases associating ectopic CS with prostate cancer have been documented. In the present study, the case of a 76-year old man suffering from castration-resistant prostate adenocarcinoma that had been treated with enzalutamide and luteinizing hormone-releasing hormone (LHRH) analogue for the last four years is presented. The patient presented to the emergency department with lower extremity muscle weakness, bradypsychia and hypokalemia. Following a thorough diagnostic evaluation, hypercortisolemia was identified. No suppression after low- and high-dose dexamethasone challenge, increased cortisol 24 h excretion and normal pituitary magnetic resonance imaging led to the diagnosis of ectopic CS. Immediate targeted therapy was initiated with adrenal steroidogenesis inhibitors, including metyrapone and ketoconazole along with chemotherapy with docetaxel and prednisolone. There was a remarkable decrease in cortisol levels within days and hospitalization was no longer required. The patient managed to complete three cycles of chemotherapy; unfortunately, he succumbed within three months of the diagnosis of ectopic CS. In the present study, all existing cases of paraneoplastic CS related to prostate cancer are reviewed. The aim of the current study was to highlight the need of early diagnosis and treatment of this entity as it may present with atypical clinical findings and potentially evolve to a life-threatening condition.

Keywords: Cushing syndrome; ectopic adrenocorticotropic hormone; neuroendocrine dedifferentiation; paraneoplastic syndrome; prostate cancer.

Figure 1.

Pituitary magnetic resonance imaging T2 with no pathological findings.

Figure 2.

(A) Response of ACTH levels with adrenal blockage therapy. ACTH reference interval: <46 pg/ml (B) Response of serum cortisol levels within 10 days of therapy with ketoconazole and metyrapone. Serum cortisol reference interval: 138–690 nmol/l. ACTH, adrenocorticotropic hormone.

Figure 3.

Flowchart presenting the successive steps during the selection of studies.