Endocrine Abstracts (2004) 7 P279

A novel 17 alpha hydroxylase mutation (CYP 17) associated with a pelvic germ cell tumour

AM Brooke1, T Ahmad4, NF Taylor2, J Shepherd3, L Lin5, JC Achermann5, G Rumsbey6, ME Gore4 & JP Monson1


1Department of Endocrinology, St. Bartholomew's and the London, Queen Mary's school of Medicine and Dentistry, University of London, London, UK; 2Department of Clinical Biochemistry, King's College Hospital, London, UK; 3Deapartment of Gynaecology, The Royal Marsden Hospital, London, UK; 4Department of Medicine, The Royal Marsden Hospital, London, UK; 5ICH and department of Medicine, University College Hospital, London, UK; 6Chemical Pathology, University College Hospital, London, UK.


A 17 year old phenotypically female Middle Eastern patient presented with a short history of abdominal pain. Laparotomy and biopsy confirmed extensive mixed germ cell tumour with yolk sac elements. After referral to London, remission was achieved with 6 cycles of Bleomycin, Etoposide and Cisplatinum (alpha feta protein decreasing from 12 714 to 5 milli units per litre). Examination revealed short stature, absent pubertal development and primary amenorrhoea. She had palmar, buccal and streak hyperpigmentation and hypertension. Serum potassium was 2.5 millimol per litre, with a serum aldosterone of 643 picomol per litre and a suppressed renin. Dehydroepiandrosterone, androstenedione, testosterone, 17 hydroxyprogesterone and 11 deoxycortisol were all low or below the assay detection limit. Serum cortisol was 15 nanomol per litre with adrenocorticotrophic hormone (ACTH) of 21 nanograms per millilitre. Serum androgens and cortisol showed no response to ACTH stimulation. Her karyotype was 46,XX, with elevated gonadotrophins and undetectable oestradiol. Computed tomography revealed bilateral adrenal hyperplasia. A clinical diagnosis of 17 alpha hydroxylase deficiency was confirmed by urine steroid chromatography profiles demonstrating grossly elevated corticosterone metabolites and pregnanediol with absent cortisol, androstenedione and DHA metabolites. Corticosterone feedback on the hypothalamic-pituitary axis explains the apparently normal levels of ACTH. Mutation analysis revealed a novel homozygous Arg96Gln missense mutation in CYP17 affecting a conserved amino acid in a putative key substrate binding region. Hypokalaemia and hypertension resolved with reverse circadian prednisolone and puberty was initiated with low dose ethinyloestradiol. Although certain disorders of sexual differentiation predispose to gonadal neoplasia, the association of 17alpha hydroxylase deficiency and germ cell neoplasia has not been described and coincidence remains possible.

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