Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The practicability and tolerability of trilostane, a competitive inhibitor of 3 beta-hydroxysteroid-delta 5-dehydrogenase, for the therapy of primary aldosteronism was assessed in 1 patient with aldosterone-producing adenoma (APA) and 3 subjects with idiopathic adrenal hyperplasia (IHA). Trilostane afforded reduction of plasma levels of aldosterone, progesterone, deoxycorticosterone, 17-OH progesterone, cortisol, delta 4-androstenedione, and urinary excretion of 17-hydroxycorticosteroid. Conversely, circulating levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and urinary excretion of 17-ketosteroids were increased following this drug therapy. Suppression of mineralo- or glucocorticoid biosynthesis was accompanied by an increase in plasma renin activity. One patient with APA or 3 subjects with IHA showed slight or remarkable improvement of hypertension and hypokalemia. Based on these findings, efficacy and tolerability of trilostane appear to aid in the treatment of IHA.
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PMID:Primary aldosteronism treated by trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor). 298 27

(2 alpha, 4 alpha, 5 alpha, 17 beta)-4, 5-[Epoxy-17-hydroxy-3-oxo-androstane-2-carbonitrile (Trilostane, Win 24450) is a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase currently being introduced into therapy of Cushing's disease and primary aldosteronism and being investigated in the treatment of low-renin essential hypertension. In adult male rats and in healthy, young, male volunteers the effect of trilostane on testosterone production was studied. Rats were treated with trilostane 150 mg or 300 mg/kg/d for 7 or 14 days. Testosterone in serum was measured by radioimmunoassay, testes were weighed and Leydig cell nuclear volume determined. In healthy volunteers, dehydroepiandrosterone sulphate (DHEAS) and responses of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone to luteinizing hormone releasing hormone (LHRH) stimulation were measured by radioimmunoassay before and during trilostane treatment (240 mg/d). In rats, trilostane treatment decreases testosterone and increases Leydig cell nuclear volumes without affecting testicular weight. In volunteers, basal testosterone is not changed during trilostane treatment but testosterone response to LHRH is impaired. DHEAS increases. LH or FSH levels are not altered. It is concluded that trilostane treatment may decrease testosterone synthesis.
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PMID:The inhibiting effect of trilostane on testosterone synthesis. Hormonal and morphologic alterations induced by subchronic trilostane treatment in rats and healthy volunteers. 640 30

An aldosterone-producing adenoma (APA) was associated with chronic renal failure. Following treatment with Trilostane (a 3 beta-hydroxysteroid dehydrogenase inhibitor), furosemide and continuous ambulatory peritoneal dialysis (CAPD), a left adrenal adenoma was successfully removed. This patient, still being treated with CAPD, is a unique example of primary aldosteronism without showing suppressed plasma renin activity.
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PMID:Primary aldosteronism associated with chronic renal failure. Report of a case. 646 82

A 58-year-old man with primary aldosteronism associated with chronic chronic renal failure was treated with CAPD, oral administrations of Trilostane and furosemide. No adverse clinical or laboratory response could be attributed to these combination therapies. After subsequent removal of aldosterone-producing adenoma from left adrenal gland, his clinical symptoms were slightly improved. This case, still received CAPD treatment, is a unique presentation for primary aldosteronism without showing suppressed plasma renin activity.
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PMID:[Therapeutic experience of primary aldosteronism associated with chronic renal failure]. 664 11

In adult male rats the effect of a subchronic treatment with trilostane, a new, orally active, competitive inhibitor of 3 beta-hydroxysteroid dehydrogenase, on adrenal steroid production and morphology was studied. Rats were treated with 150 mg or 300 mg trilostane/kg/day for 7 or 14 days and with 150 mg trilostane/kg/day for 10 days in combination with 75 mg propranolol/kg/day or 1 mg indomethacin/kg/day. Trilostane leads to a dose-dependent increase in adrenal weight and to a rather uniform increase in nuclear volumes of zona glomerulosa and zona fasciculata cells. The basal secretion of aldosterone and corticosterone is not significantly altered. Trilostane increases the excretion of sodium and potassium in urine. The stimulating effect of trilostane on plasma renin activity and the adrenal enlargement are not inhibited by propranolol or indomethacin. We conclude that trilostane induces latent adrenal insufficiency. Increased renin and ACTH maintain normal basal steroid levels, and might impair the therapeutic effectiveness of trilostane.
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PMID:The inhibiting effect of trilostane on adrenal steroid synthesis: hormonal and morphological alterations induced by subchronic trilostane treatment in normal rats. 704 68

Here we report a case of a renin-producing adrenocortical carcinoma. A 57-year-old woman was referred to our hospital complaining of thirst and generalized muscle weakness. She was diagnosed as being hypertensive and diabetic with associated hypokalemia and she had a hard elastic mass with a diameter of 10 cm on the left side of her neck. An abdominal computed tomography scan revealed a suprarenal mass on the left side (8.5 x 8 x 6.5 cm). Endocrinological examination demonstrated a marked elevation in the patient's serum glucocorticoid and sex steroid hormones as well as plasma renin activity. Histological examination of a sample taken from the neck mass revealed a metastasis from an adrenal carcinoma, which was stained positively with antibodies against cytochrome P450 and renin, establishing the diagnosis of a renin-producing adrenocortical carcinoma. Trilostane was effective in reducing serum cortisol levels, but mitotane was ineffective.
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PMID:A case of renin-producing adrenocortical cancer. 1094 35

The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (+/-SD) dose rate of trilostane to achieve good clinical control was 2.8+/-1.0mg/kg bodyweight. Trilostane treatment resulted in a significant decline in basal plasma cortisol concentrations. The median plasma ACTH concentration (39 pmol/L, range 7-132 pmol/L; n=60) at the optimal trilostane dosage time was significantly higher (P<0.001) than before treatment (13 pmol/L, range 2-102 pmol/L). These values did not overlap with plasma ACTH concentrations (range 212-307 pmol/L) of five PDH dogs with trilostane-induced hypocortisolism. The median cortisol/ACTH ratio in well-controlled dogs (0.23, range 0.03-2.5; n=46) was significantly lower (P<0.001) than before treatment (2.59, range 0.27-13.25). Trilostane treatment resulted in an insignificant decrease in plasma aldosterone concentration (PAC), but the median plasma renin activity (PRA) at the time the trilostane dosage was considered optimal (265 fmol/L/s, range 70-3280 fmol/L/s; n=18) was significantly higher (P<0.001) than prior to treatment (115 fmol/L/s, range 15-1330 fmol/L/s). Similarly, the median PAC/PRA ratio during trilostane treatment (0.16, range 0.003-0.92; n=17) was significantly lower (P<0.001) than before treatment (median 0.44, range 0.04-1.33). Trilostane affected both the hypothalamic-pituitary-adrenocortical and the renin-aldosterone axes. The results also suggested that basal plasma ACTH concentration may be used to detect trilostane overdosage.
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PMID:Effects of trilostane on the pituitary-adrenocortical and renin-aldosterone axis in dogs with pituitary-dependent hypercortisolism. 1904 43