cosyntropin and Prostatic-Neoplasms

Topics: Buserelin; Castration; Chorionic Gonadotropin; Cosyntropin; Dexamethasone; Diethylstilbestrol; Estrogens; Goserelin; Hormones; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

During a Phase I trial of suramin, a novel antineoplastic agent with activity against hormone-refractory prostate carcinoma, the authors observed two patients with clinical mineralocorticoid insufficiency in spite of hydrocortisone replacement therapy.. The authors retrospectively assessed adrenal cortical function in 20 such patients via adrenocorticotropic stimulation testing, measuring both cortisol and aldosterone responses, either at the time or treatment of immediately after discontinuation of treatment.. Two of 9 patients (22%) treated at relatively low dose levels (< or = 1200 mg/m2 on Day 1) demonstrated adrenal cortical insufficiency, as compared with 9 of 11 patients (32%) treated with relatively high doses (> 1200 mg/m2 on Day 1) (P = 0.03 by 1-tailed Fisher's exact test). There appeared to be a cumulative dose-response relationship to the development of glucocorticoid insufficiency, with no instances being observed at doses < 4.8 g/m2 and uniform toxicity occurring at doses > 7.6 g/m2. Long term glucocorticoid insufficiency was present in 1 of 5 patients (20%) tested at an interval of > 90 days after discontinuation of suramin treatment. All instances of glucocorticoid insufficiency were associated with mineralocorticoid insufficiency. Suramin did not affect the absorption or excretion of exogenously administered glucocorticoid in one patient.. Suramin causes both primary mineralocorticoid and primary glucocorticoid insufficiency. This may occur in a dose-dependent manner. Long term glucocorticoid insufficiency appears to occur in a minority of patients treated with low doses of suramin. Patients receiving high doses of suramin for treatment of advanced carcinoma should receive at least physiologic replacement doses of both mineralocorticoid and glucocorticoid. Higher doses of glucocorticoid may be required in selected patients.

Topics: Addison Disease; Adrenal Cortex Diseases; Adrenocorticotropic Hormone; Aged; Aldosterone; Antineoplastic Agents; Cosyntropin; Drug Administration Schedule; Humans; Hydrocortisone; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Suramin

A patient with stage D prostatic cancer but in reasonably good general health was discovered to have adrenal failure and tumor destruction of the adrenal glands. Because prostatic cancer is common and compatible with prolonged survival, we surveyed other patients with stage D prostatic cancer. On initial screening with the cosyntropin test, we found that 5 of 14 patients failed to respond with an increase in serum cortisol of 10 micrograms/dL, suggesting an adrenal failure incidence of 36%. Retesting, however, indicated that probably all of these were false-positive results.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Adrenal Insufficiency; Cosyntropin; False Positive Reactions; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms

Ketoconazole is an antifungal agent that, in high doses, inhibits testicular and adrenal steroid synthesis. The ability of ketoconazole to block steroid synthesis has prompted us to use it in the treatment of advanced prostatic carcinoma. This study was designed to determine the site of steroid synthetic blockade that was induced by ketoconazole. Twelve patients with metastatic prostate carcinoma on long term high dose ketoconazole therapy were compared with 12 control volunteers. Values of serum progesterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulphate, testosterone, and cortisol were measured in a baseline state and after Cosyntropin and human chorionic gonadotropin stimulation. Baseline data showed that serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulphate were lower and that plasma progesterone, luteinizing hormone, and adrenocorticotropin were higher in the ketoconazole group. With Cosyntropin, plasma cortisol, androstenedione, and dehydroepiandrosterone sulphate increased only in the control group. With human chorionic gonadotropin, testosterone increased only in the control group. Basal 17-hydroxyprogesterone and progesterone rose after Cosyntropin only in the ketoconazole group. Following human chorionic gonadotropin, progesterone rose in the ketoconazole group but not in the control group. These results suggest that ketoconazole is a potent inhibitor of steroid synthesis. The major site of action appears to be in the inhibition of 17-20 desmolase. A moderate blockade of 17-hydroxylase may be present. There is a marked inhibition of 21- and/or 11-hydroxylase. The ability of ketoconazole to inhibit steroid synthesis should have therapeutic potential in the treatment of steroid dependent disease. Frequent high dose ketoconazole therapy can inhibit adrenal steroid synthesis, which can be important for patients undergoing stressful situations.

Topics: 17-alpha-Hydroxyprogesterone; Aged; Aldehyde-Lyases; Androgens; Androstenedione; Chorionic Gonadotropin; Cosyntropin; Cytochrome P-450 Enzyme Inhibitors; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Humans; Hydrocortisone; Hydroxyprogesterones; Ketoconazole; Male; Progesterone; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Testosterone

The effect of Synacthen (beta1-24-corticotrophin) on plasma testosterone and 4-androstene-3, 17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients. The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH.

Topics: Adrenocorticotropic Hormone; Androstenedione; Cosyntropin; Cross Reactions; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms; Stimulation, Chemical; Testosterone

Topics: Adrenocorticotropic Hormone; Cosyntropin; Humans; Male; Middle Aged; Prostatic Neoplasms

Topics: Adrenal Cortex; Adrenal Glands; Aged; Castration; Cosyntropin; Dexamethasone; Diethylstilbestrol; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone