Conversion of hydrocortisone to estrogen in carcinoma of the breast after oophorectomy and adrenalectomy.

PIP: This case report concerns a 52-year-old woman who underwent radical mastectomy. Microscopic study revealed the tumor to be infiltrating ductal carcinoma. Axillary lymph nodes contained metastatic tumor. About a year later tumor recurrence was demonstrated in the lumbar vertebrae. The disease progressed under local irradiation. After another year bilateral oophorectomy and adrenalectomy were performed. The patient died about 17 months after the last surgery with widespread metastatic disease. This study was conducted with the patient on hydrocortisone replacement therapy beginning about 1 month after removal of the ovaries and adrenal glands. 5 microcuries of 4-14C-hydrocortisone were administered and 3 successive 24-hour urine specimens were collected and kept frozen. The steroid conjugates were extracted from the urine, hydrolyzed, and the free steroids removed by solvent extraction. The estrogen fraction from the urine was separated by sodium hydroxide extraction and purified by counter-current distribution, then analyzed. It was found that the administered 4-14C-hydrocortisone was converted to 11 beta-hydroxyestradiol which possesses estrogenic activity. The identified conversion product represented 5% of the radioactivity of all the extracts and .7% of the total administered radioactivity. Other metabolic products of hydrocortisone isolated included cortol, urocortisol, and cortolone. The site of conversion and the mechanisms involved require further study. Such conversion to estrogens of circulating hormone used in adrenal replacement therapy could affect the mammary malignancies of these patients.^ieng