Isolation of Δ3:5-androstadiene-17-one from the urine of a man with a malignant tumour of the adrenal cortex

Abstract

HYPERPLASIA or neoplasia of the adrenal gland, as is well known, may cause changes in the accessory sexual attributes of the patient. The changes differ in the two sexes. In women, in whom these adrenal disorders are more frequent than in men, virilism is commonly produced: coarse hair grows on the face and other parts of the body where its distribution comes to resemble that of the male, the breasts and genitalia atrophy, the menses no longer appear and the voice may become masculine in tone. In men, on the other hand, feminism may be caused by these adrenal disturbances: the hair of the face becomes scanty, the breasts swell and may even produce milk, the testes and genitalia atrophy and impotence ensues. Hypothetically the changes thus produced might be attributed to an incorrect proportion between the male and female hormones. An increased output of male hormone has been found in the urine of females suffering from adrenal virilism. In the case of adrenal feminism in a male about to be described there was an increased output of oestrogenic hormone. This excessive production of oestrogenic material had not hitherto been observed in a male with an adrenal tumour, though Frank [1934] has recorded two cases of adrenal tumour in women accompanied by an excessive output of oestrogenic hormone. The primary object of the work now described was the isolation and identification of the oestrogenic hormone. The following are brief clinical notes. The patient, a man of 34 years, was under the care of Dr Levy Simpson. An adrenal tumour was present and caused signs of feminism: the breasts were enlarged, the testes reduced in size and there was impotence. The adrenal tumour was removed by Mr C. A. Joll on 22 July 1934, and weighed 660 g. A specimen of urine passed on the morning of that day and submitted to qualitative tests showed an absence of the prolan reaction and the presence of oestrogenic hormone in a concentration of at least 500 mouse units per litre. At the operation the tumour was found to have invaded the adrenal vein; recurrence of the growth therefore seemed likely. After removal of the tumour the excessive output of oestrogen ceased for a while. In February 1936, however, it became clear that metastatic growths were present, and from this date until the patient's death, 3 months later, his urine was collected for analysis, some 30 1. in all being obtained. Isolation of new "hormones" After hydrolysis of the urine with hydrochloric acid, an assay of the oestro- genic hormone gave a value of approximately 3000 i.U. per 1. We have not our- selves estimated the male hormone content, but a sample of urine from this ( 950 )