1-OXYGENATED STEROIDS IN THE URINE OF A HYPERTENSIVE, VIRILIZED INFANT WITH ADRENOCORTICAL CARCINOMA
R. W. H. EDWARDS,* G. J. A. I. SNODGRASS; AND J. R. DALY}
* Endocrine Laboratory, Institute of Child Health, 30 Guilford Street, London, WCIN 1EH and t Departments of Pediatrics and Chemical Pathology, Charing Cross Group of Hospitals, Fulham, London, W. 6
(Received 20 August 1970)
1-Oxygenated steroids were recognized during preliminary characterization of substances isolated from the urine of two hypertensive infants (Edwards, Harvey & Knight-Jones, 1968; Edwards & Trafford, 1968) with raised values of the steroid 11- oxygenation index (Edwards, Makin & Barrett, 1964; B. E. Clayton, R. W. H. Edwards & H. L. J. Makin, in preparation). Shortly afterwards, Gower, Daly, Snodgrass & Stern (1970) described a 15-month-old female child with a virilizing adrenocortical carcinoma, who was excreting large quantities of dehydroepiandrosterone and monofunctional C19-416-steroids together with increased quantities of testosterone, oestrogens and pregnanediol. Since this child was also hypertensive (blood pressure ranged from 160/85 to 180/115 mmHg) and had a urinary steroid 11-oxygenation index of 1.3 (upper limit of normal 0.7 at the 90% level) it was decided to look for 1-oxygenated steroids in her urine.
Examination of qualitative, two-dimensional paper chromatograms (Edwards, 1968) of urinary extracts with the styryl tetrazolium location reagent revealed substances with essentially the same slow reaction and appearance as those of the earlier patients. Also, the Zimmermann reagent produced the red colour characteristic of 17-hydroxy-20-oxosteroids.
Gas-liquid chromatography (GLC) (unpublished observations of H. L. J. Makin & D. J. H. Trafford) of the preoperative urinary steroids after borohydride reduction, periodate oxidation (Few, 1961) and formylation (Makin, 1970) showed the presence of the substances with the same retention times as la, 3a-dihydroxy-53-androstan- 17-one and la,3a,17a-trihydroxy-50-androstane. These substances had not been observed during GLC of urinary extracts from other patients or healthy subjects.
At the operation a 50 g adrenocortical carcinoma was removed and the child was sent home well after 3 weeks. The postoperative blood pressure has remained normal for 2 years, and three urine samples examined during that time, by the paper chroma- tographic or the GLC procedures, showed no sign of 1-oxygenated steroids. Since both hypertension and excretion of 1-oxygenated steroids were abolished by removal of the adrenocortical carcinoma it is likely that a I-oxygenated steroid, although not necessarily one of the urinary steroids, had a pressor effect. It is also likely that the 1-oxygenated steroids arose in malignant adrenocortical tissue.
182 R. W. H. EDWARDS, G. J. A. I. SNODGRASS AND J. R. DALY
REFERENCES
Edwards, R. W. H. (1968). In Chromotographic and electrophoretic techniques, third edn, vol. I, p. 538. Ed. I. Smith. London: Heinemann.
Edwards, R. W. H., Harvey, D. R. & Knight-Jones, E. (1968). Archs Dis. Childh. 43, 611-615.
Edwards, R. W. H., Makin, H. L. J. & Barrett, T. M. (1964). J. Endocr. 30, 181-194.
Edwards, R. W. H. & Trafford, D. J. H. (1968). Biochem. J. 108, 185-193.
Few, J. D. (1961). J. Endocr. 22, 31-46.
Gower, D. B., Daly, J. R., Snodgrass, G. J. I. A. & Stern, M. I. (1970). Acta endocr., Copenh. 63, 562-576. Makin, H. L. J. (1970). J. Endocr. 47, 55-64.