Clinical study on adrenal suppression and estrogens in recurrent breast cancer

Abstract

The surgical adrenalectomy has been shown to improve clinical signs in the patients with metastatic breast cancer. It was also reported by a few workers that chemical or medical adrenalectomy had similar effects on the patients. In these reports, it was pointed out that the administration of hydrocortisone or synthetic glucocorticoids in larger doses could not be continued, because side effects of these agents soon appeared. On the other hand, it has never been proved that urinary adrenal estrogens remarkably diminished or disappeared during medical adrenalectomy, because the quantitative determination of adrenal estrogens has not been established. In this study, I intended to clarify whether or not urinary adrenal estrogens disappeared during medical adrenalectomy in castrated cases with metastatic breast cancer, when doses of synthetic glucocorticoids were administered with few dominant side effects.Fourteen cases with metastatic breast cancer, 13 cases surgically castrated and 1 case postmenopausal, were studied. Doses of three to six mg/24 hrs. of Paramethasone were administered during 3 weeks and 1 to 2 mg/24 hrs. successively. The administration had no side effects, except for slight obesity in some cases.Urinary 17-hydroxycorticosteroids (17-0HCS) and 17-ketosteroids (17-KS) were quantitatively determined by the method of Seki & Matsumoto (1963). Urinary estrogens were quantitatively determined by the method of Matsumoto & Seki (1963), but impurity from the urine disturbed the exact determination of small amounts of adrenal estrogens in some cases. So, each estrogen fraction was further purified by a partition chromatography on Dowex50w × 4. Purified phenolic fraction was separated on Dowex50w × 4 as a stationary phase using a mixture of ethanol, benzene, hexane and water (30 : 100 : 40 : 1, by vol.) as a moving phase. Estriol fraction containing little fluorescence background was added with diluted sulfuric acid and determined fluorimetrically. The estrone and estradiol-17β fractions were further purified by the elution chromatography on Amberlite IRC-50 using a mixture of ethanol and water (3 : 2, by vol.) as a eluent and determined fluorimetrically. The fluorescence background caused by urine in each estrogen fraction was so small that 0.1 to 0.2μg/24 hrs. of each estrogen could be determined by the method.With these methods, following data were obtained.17-0HCS 17-KS Estrogens before administration 2636 ± 287 1426 ± 267 3.4 ± 0.8after administration 238± 33 191 57 1.0 0.2after administration 'negligible' 40% (18/45) 71% (32/45) 74% (20/27) (μg/24 hrs.) From the data, it was concluded that urinary adrenal estrogens diminished as remarkably as urinary 17-hydroxycorticosteroids and 17-ketosteroids or almost disappeared during medical adrenalectomy, with the administration of doses of Paramethasone with few dominant side effects.