Endocrine Abstracts

Cushing’s syndrome due to ectopic ACTH production is extremely rare in childhood. Ectopic ACTH secretion is most often due to tumours in the chest, but rare cases of carcinoid tumours, neuroblastoma, phaeochromocytoma and pancreatic and ovarian carcinoma have been reported. We describe a 2 year old girl with ectopic Cushing’s syndrome due to a malignant epithelial abdominal tumour producing POMC. She presented with rapid weight gain, hypertension, body odour, lethargy and moodiness. Urinary cortisol excretion was severely elevated. Cortisol was partly suppressed on low (22%) and high dose dexamethasone (43%) suppression test. CRH test results (12% increase in ACTH) suggested ectopic ACTH secretion. Further imaging led to the identification of an abdominal tumour with marked peritoneal infiltration secreting AFP. Histology revealed a malignant yolk sac tumour, strongly expressing AE1/3 (a pancytokeratin marker) but not CD117, Oct3/4, CD56, desmin, WT1 and S100.

Posttranslational processing of POMC results in the generation of ACTH, the N-terminal POMC fragment, and β-lipotrophin which is cleaved to β-endorphin (bEP). Circulating POMC concentrations (measured by specific ELISA) were increased and then decreased during chemotherapy, whereas ACTH (measured by ELISA which cross-reacts 1% with POMC) concentrations were not elevated. Immunohistochemistry of the tumour utilised antibodies recognising POMC (N1C11) or POMC+ACTH (A1A12) or ACTH and not POMC (A2A3) or, POMC+ β-LPH + bEP but not ACTH, (E6B2). This immunohistochemistry also suggested that POMC rather than ACTH was being produced by the tumour. Chemotherapy led to a reduction in tumour mass, AFP concentration and features of Cushing’s syndrome.

To conclude, we describe a malignant yolk sac tumour as a new source of ectopic POMC production leading to Cushing’s Syndrome in a young girl. Our data suggest that POMC is stimulating cortisol production either directly by binding to the adrenal ACTH receptor or after cleavage within the adrenal to generate ACTH.