ESA-SRB-AOTA 2019

Ectopic adrenocorticotropic hormone syndrome secondary to prostate carcinoma: an uncommon cause of Cushing’s syndrome (#584)

Kay Hau Choy 1 , Alexia Pape 2
  1. Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, NSW, Australia
  2. Department of Endocrinology, Wollongong Hospital, ISLHD, Wollongong, NSW, Australia

A 67-year-old male with hormone-refractory metastatic prostate carcinoma was admitted with back pain due to pathological vertebral fractures, recent onset weight gain and increasing pedal oedema. His admission was complicated by profound hypokalaemia, metabolic alkalosis, new onset insulin-requiring diabetes, resistant hypertension requiring multiple antihypertensives and worsening thrombocytopaenia. Cushing’s syndrome (CS) due to ectopic adrenocorticotropin secretion (EAS) was confirmed (table), as evidenced by failure of cortisol suppression following low-dose dexamethasone administration, with significantly raised adrenocorticotropic hormone, markedly elevated urinary free cortisol and absence of pituitary adenoma on neuroimaging. However, he lacked the typical signs of CS. Computed tomography demonstrated bilateral adrenal gland hypertrophy. Investigation for thrombocytopaenia revealed bone marrow infiltration by neuroendocrine tumour with prostatic markers, reflecting neuroendocrine differentiation of the pre-existing prostate carcinoma. Hypercortisolaemia and its consequent metabolic derangements were temporarily controlled with metyrapone. He was a poor surgical candidate and subsequently received palliative-intent chemotherapy. He died two months later from respiratory sepsis.

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Prostate carcinoma is a rare cause of EAS.1 Neuroendocrine differentiation in prostate cancer can result in concomitant ectopic hormone production and is associated with tumour progression and poor prognosis.2 Several cases of EAS in prostate cancer have been reported and the common features included metabolic alkalosis, hypokalaemia, hypertension and lack of classic somatic signs of CS.1-4 Treatment modalities of EAS are limited, as definitive management is surgical, either with excision of primary tumour, bilateral adrenalectomy or both. Despite previous reports showing temporary biochemical control of hypercortisolism with adrenal steroidogenesis inhibitors, there is limited evidence that medical therapy is effective in lengthening survival of affected individuals.2-5 Of cases where the cause of death was reported, most patients died from sepsis, likely due to uncontrolled hypercortisolaemia.1-4 Our case highlights the clinical presentation of EAS in prostate cancer and illustrates its diagnostic and treatment challenges.  

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