Cushing's syndrome due to POMC secretion from a malignant yolk sac tumor in a two year old child

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 632-648-Pediatric Growth Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-640
Evelien F Gevers*1, Pratik Shah2, Suzanne Meredith3, John Torpiano4, Catherine J Peters2, Neil Sebire2, Anne White3, Olga Slater2 and Mehul Tulsidas Dattani5
1Erasmus Med Ctr-Sopia Childrens, Rotterdam, Netherlands, 2Great Ormond Street Hospital, London, United Kingdom, 3University of Manchester, Manchester, United Kingdom, 4Mater Dei Hospital, Malta, Malta, 5UCL Institute of Child Health, London, United Kingdom
Background: Cushing's syndrome due to ectopic ACTH production is extremely rare in childhood and is most often due to tumors in the chest. Rare cases of carcinoid tumors, neuroblastoma, phaeochromocytoma and pancreatic and ovarian carcinoma have been described. We describe an abdominal malignant epithelial / yolk sac tumor producing POMC causing Cushing's syndrome in a child.

Clinical Case: A 2yr old girl 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 tests. CRH test results (12% increase in ACTH) suggested ectopic ACTH secretion. Further imaging led to the identification of an abdominal tumor with marked peritoneal infiltration secreting α-feto protein (AFP, >300,000 kU/l). Histology revealed a malignant epithelial tumor, 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 beta-lipotropin which is cleaved to produce gamma-lipotropin and beta-endorphin. Monoclonal antibodies recognising POMC (N1C11) or POMC and ACTH (A1A12) or the C-terminal splicing site of ACTH specifically (A2A3) were used to assess products produced by the tumor. Plasma ACTH precursors but not ACTH concentrations were increased, and this decreased during chemotherapy. Immunohistochemistry with the same antibodies and E6B2, which recognises POMC and beta-LPH but not ACTH, also suggested ACTH precursors but not ACTH production by the tumor. Our data suggest that either POMC binds to the adrenal ACTH receptor or that POMC is cleaved within the adrenal to generate ACTH. Chemotherapy led to a temporary reduction in tumor mass, AFP and cortisol production with improvement of Cushingoid features. Repeat biopsy showed a yolk sac tumor.

Conclusion: We describe a malignant yolk sac tumor as a novel source of ectopic POMC production leading to Cushing's syndrome in a young girl.

Nothing to Disclose: EFG, PS, SM, JT, CJP, NS, AW, OS, MTD

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