title: Favourable response of a virilizing adrenocortical carcinoma to preoperative treatment with ketoconazole and postoperative chemotherapy.
abstract: A 25-year-old woman presented with an extensive adrenocortical carcinoma with severe virilization and mild Cushing's syndrome. In the tumour there was a primacy of the P450C17 (17,20-lyase) over the P450C21 (21-hydroxylase) route, favouring the synthesis of androgens over corticoids. Preoperatively, the patient was treated with the antimycotic agent ketoconazole, a known inhibitor of steroid synthesis, at a dose of 600 mg/day and after a week 1200 mg/day, to reduce operation risks and to achieve a better metabolic control. This treatment markedly decreased hyperandrogenism and normalized the hypercortisolism. The main effect of ketoconazole was at the 17,20-lyase level and probably at a locus prior in steroidogenesis, i.e. at the P450SCC and/or 17 alpha-hydroxylase level. In contrast with other studies no effect at all was seen on the 11-hydroxylase activity of P450C11. After removal of a massive adrenal carcinoma, extending into the vena cava, vena cava resection and hemihepatectomy because of liver invasion, plasma cortisol and androgen values normalized. Despite adjuvant chemotherapy with o,p'-dichlor-diphenyl-dichloretan (4000 mg daily) hyperandrogenism soon recurred and lung metastases became manifest. Within 2 months after starting combined chemotherapy with 5-fluorouracil, cisplatin, and doxorubicin lung metastases almost completely disappeared with clinical and biochemical resolution of the hyperandrogenic state.
authors.affiliation: Department of Medicine, University of Nijmegen, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Kruimel
authors.forename: A G
authors.initials: AG
authors.lastname: Smals
authors.forename: L V
authors.initials: LV
authors.lastname: Beex
authors.forename: L M
authors.initials: LM
authors.lastname: Swinkels
authors.forename: G F
authors.initials: GF
authors.lastname: Pieters
authors.forename: P W
authors.initials: PW
authors.lastname: Kloppenborg
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D000328:Adult; D000446:Aldehyde-Lyases / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D003480:Cushing Syndrome / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007654:Ketoconazole / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D011182:Postoperative Care; D011300:Preoperative Care; D013254:Steroid 17-alpha-Hydroxylase; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D014770:Virilism / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000728:Androgens; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases; D007654:Ketoconazole; D006854:Hydrocortisone