Metyrapone administered orally (Liddle, Estep, Kendall, Williams & Townes, 1959) or intravenously (Gold, Di Raimondo & Forsham, 1960) has been widely used as a test of corticotrophin (ACTH) reserve. Although both modes of administration are thought to be equally satisfactory (Gold, Kent & Forsham, 1961) a comparison in the same subjects has not been reported.The subjects (10 men and 4 women) received first an infusion of 30 mg. metyrapone/ kg. body weight (Metopirone, Ciba) in 0\m=.\9 % NaCl solution at the rate of 125 ml./hr. for 4 hr. starting between 8.00 and 9.00 hr. Urine collections were started at the same time. The oral test was performed 5\p=n-\7 days later, eight doses of two 250 mg. capsules being taken every 2\p=n-\3hr. Total 17-oxogenic steroid (17-OGS) excretion was estimated by the method of Few (1961).The results are shown in Table 1. After i.v. administration of metyrapone the rise in urinary 17-OGS during the following 24 hr. ranged from 2\m=.\1to 13\m=.\1 mg. but one patient showed a reduction in the 17-OGS excretion. The values after oral ingestion of the drug showed increases ranging from 4-0 to 73-2 mg. The mean increase in the i.v. test was 4-7 + 4-3 (s.E.) mg. (47% above control level); oral administration resulted in a mean increase of 24-4 + 21-1 mg. ( + 132 %). Table 1 shows that if a 100% increase in 17-OGS excretion is considered as a positive response, then six cases out of 14 (nos. 1, 3, 6, 9, 10 and 12) showed such a response in the oral test, when i.v. tests gave a falsely negative response.When urine specimens of patients undergoing an i.v. test were collected for 12 hr., 17-OGS excretion was not evenly distributed, with the exception of a few cases. Larger amounts of corticosteroids were excreted in the first 12 hr. (13 out of 22 cases) but the difference was not significant (P > 0-05).According to these results there is no advantage in fractionating the 24 hr. urine sample in order to obtain a peak of steroid excretion after the injection of metyrapone.The value of oral metyrapone tests in the diagnosis of pituitary insufficiency is well established. Gold et al. (1961) have stated that 30 mg. metyrapone bitartrate infused into healthy subjects for 4 hr. caused an increase of 100 % over the basal values of both the urinary 17-hydroxycorticosteroids and 17-ketogenic steroids in the 24 hr. after the infusion.
The effect of short term bromocriptine (5 mg/day, 5 days) on plasma epinephrine (E), norepinephrine (NE), dopamine (DA) and prolactin (PRL) was studied in 4 normal women and 6 bearing PRL-secreting tumors. When studied on placebo no significant differences were found between controls and patients in E, NE and DA plasma levels. Bromocriptine induced: a 70% decrease in PRL levels in both groups, a significant (p less than 0.05) decrease in plasma NE levels in the control group, no significant change in plasma NE levels in the hyperprolactinemic patients when considered as a group. These results do not indicate that bromocriptine is a useful tool in the diagnosis of defective central dopaminergic regulation since individual responses of the PRL-secreting tumor patients were variable. Nevertheless, the impaired response of the group as a whole may be suggesting an underlying alteration of DA2 receptor activity in these tumor patients.
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