Clomiphene-Test for Evaluation of Residual Pituitary Activity after Yttrium Implantation in Patients with Advanced Breast Carcinoma

Abstract

It has been suggested that tumor regression following hypophyseal implantation of Yttrium sources is not always related to the endocrine effect of this procedure. It has been observed that although relief of pain was obtained in the majority of patients with bone metastases from breast cancer with hypophyseal implantation of radioactive Yttrium, only a small proportion showed endocrinological evidence of complete hypophyseal destruction. Nevertheless, it has been shown that patients with tumor regression after hypophyseal irradiation included a higher proportion with a marked fall in gonadotropin excretion than did the non-responding patients. In order to obtain more information on the residual pituitary ability to synthesize gonadotropins, after hypophyseal implantation of Yttrium, oral Clomiphene was administered to 3 women with advanced breast cancer treated by implantation of radioactive Yttrium twenty days before. One of these patients (12R-50) was subjected to bilateral ovariectomy 4 years before Yttrium implantation. In another patient (11R-61) the Clomiphene-test was done seven months after hypophyseal irradiation with Yttrium. The dose of Clomiphene used was 100 mg daily for five days. Urinary interstitial cell stimulating hormone (ICSH), determined by using competitive hemoagglutination based upon the cross-reaction between the antiserum to HCG and ICSH, estrogens (estrone and estradiol-17beta) and testosterone were determined before hand, after 5 days of treatment with Clomiphene (500 mg) and 4 days after clomiphene therapy. In all patients before clomiphene therapy, ICSH was present in the urine and its value was very elevated in the patient treated with Yttrium implantation 7 months before. After Clomiphene therapy, at 5th day of treatment, in three patients instead of observing, as expected, a rise in ICSH output, a rise in urinary estrogens was shown, together with a decrease in the urinary ICSH level. In these patients 4 days after Clomiphene therapy the urinary level of ICSH increased to high levels, whereas the estrogen level decreased. We suggest that Clomiphene acted upon the ovaries of these patients and the adrenals giving up an increase in urinary estrogens which inhibited the progressive rise of ICSH. In the absence of ovarian or adrenal activity, as in case (12R-59), shown by the absence of estrogens before and during Clomiphene therapy, Clomiphene can induce an early rise in urinary ICSH. There is still uncertainty as to the site of action of Clomiphene and two basic hormone changes have been put forward, one an initial rise in estrogens, the other a primary increase in gonadotropins. From our data we presume that either the hypothalamic-pituitary axis or ovary and adrenals may be the target organ for clomiphene. In this way the Clomiphene-test would give not only better information on the residual pituitary activity after radiological (or surgical) ablation but also on the relationship between the pituitary and peripheral endocrine organs in breast cancer patients.