ESA-SRB-AOTA 2019

Introduction:
Ectopic ACTH/CRH production accounts for <5% of cases of Cushing’s syndrome. We describe two patients with neuroendocrine small cell transformation of prostate adenocarcinoma leading to ectopic Cushing’s syndrome. This is a rare cause of ectopic Cushings’ syndrome with only 30 cases reported in the literature.  

Case 1:
An 81-year-old gentleman presented with dyspnoea, lower limb oedema and weight loss over four weeks. He had a history of prostate cancer, which was treated with androgen deprivation therapy. His investigations were consistent with ACTH dependent Cushing’s syndrome due to an ectopic source (Table 1).

FDG-PET showed a lesion in the prostatic bed. Biopsy revealed small cell neuroendocrine tumour. He was commenced on metyrapone and ketoconazole therapy for hypercortisolism. He developed brachiocephalic vein thrombosis and hospital acquired pneumonia. He declined palliative treatment, after which  he survived a further 26 days before succumbing to his illness 64 days after presentation.

Case 2:
A 70-year-old gentleman presented with facial and peripheral oedema, and cognitive decline. He had a history of prostate cancer treated with prostatectomy in 2010 followed by salvage radiotherapy and androgen deprivation therapy. He then had bicalutamide therapy but required docetaxel chemotherapy six months before presentation. Investigations were consistent with ACTH dependent Cushing’s syndrome due to an ectopic source (Table 2).

CT scan revealed subtle hypodense lesions within the liver; when biopsied they showed high grade neuroendocrine metastases. Metyrapone was trialled unsuccessfully. Chemotherapy normalised cortisol levels but was complicated by pancytopenia and urosepsis. He was then commenced on goserelin. ACTH-dependent hypercortisolism recurred six months later with abiraterone trialled unsuccessfully. A palliative approach was adopted and he died twelve months after presentation.

Conclusions:
Prostate cancers have the potential for neuroendocrine transformation. These two cases illustrate the difficulties controlling both the underlying malignancy and hypercortisolism.