A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1


avatar Gul Bano 1 , * , avatar Farheen Mir 2 , avatar Nigel Beharry 3 , avatar Philip Wilson 4 , avatar Shirley Hodgson 5 , avatar Stephen Schey 6

Cellular and Molecular Medicine, St Georges University of London, [email protected], UK
Department of Paediatrics, Watford General Hospital, UK
Department of Radiology, St. George\'s Health NHS Trust, UK
Department of Cellular pathology, St. George\'s Healthcare NHS Trust, UK
Clinical Developmental Sciences, St Georges University of London, UK
Department of Haematology, Kings College London, SE5 9RS, UK

how to cite: Bano G, Mir F, Beharry N, Wilson P, Hodgson S, et al. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1. Int J Endocrinol Metab.11(1): 52-56. doi: 10.5812/ijem.6898.


A 64-year-old male presented with neurofibromatosis 1 and Cushings syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushings secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib.

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