J. Sancho

Ovarian suppression with triptorelin and adrenal stimulation with adrenocorticotropin in functional hyperadrogenism : role of adrenal and ovarian cytochrome P450C17α

OBJECTIVESnTo validate combined ovarian suppression with triptorelin and adrenal stimulation with ACTH in the diagnosis of female hyperandrogenism and to provide new insights into the adrenal-ovarian relationship present in this disorder.nnnDESIGNnComparison of sexual steroids and basal and ACTH-stimulated steroid levels before and after ovarian suppression induced by triptorelin.nnnSETTINGnDepartment of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.nnnPARTICIPANTSnThirty-nine nonselected women with hyperandrogenism.nnnMAIN OUTCOME MEASURESnSerum levels of T, 17-hydroxyprogesterone (17-OHP), 17-hydroxy-pregnenolone, DHEA and DHEAS, androstenedione (delta 4-A), 11-deoxycortisol, and cortisol.nnnRESULTSnElevated T independent of ovarian suppression pointed to an adrenal disorder in six patients (one with an androgen-producing adenoma, two with late-onset 21-hydroxylase deficiency, three with functional adrenal hyperandrogenism). Nineteen patients had functional ovarian hyperandrogenism as elevated T normalized after ovarian suppression and were subdivided into ovDHEAS+ (n = 7) and ovDHEAS = (n = 12) subgroups depending on the presence of DHEAS hypersecretion. Finally, 14 patients had idiopathic hirsutism according to normal T before and after ovarian suppression. Comparisons of initial hormonal values between groups and with reference values obtained from normal women (n = 11) disclosed in functional adrenal hyperandrogenism an elevation of T and basal and stimulated DHEAS, delta 4-A, and 17-OHP with respect to normal women. These abnormalities were also present in ovDHEAS+ except for basal delta 4-A, which was normal, whereas only T and stimulated 17-OHP were elevated in ovDHEAS =. In the idiopathic group all steroids were normal with the exception of a mild elevation in stimulated DHEAS.nnnCONCLUSIONSnThese results show a continuum of abnormalities in hyperandrogenic women, suggesting an enhanced cytochrome P450c17 alpha activity in the adrenal and the ovary as the shared mechanism between functional adrenal hyperandrogenism and functional ovarian hyperandrogenism.

The Role of Urinary PGE2 and Renin-Angiotensin-Aldosterone System in the Pathogenesis of Essential Hypertension

In a group of 26 patients diagnosed as essential hypertensive (EH) and in a control group (CG) of 27 normotensive volunteers the urinary excretion of PGE2, plasma renin activity (PRA) and plasma aldosterone were measured. EH patients were classified into normoreninemic (NREH) (n = 21) and hyporeninemic (LREH) (n = 5) by the response of PRA to the combined stimuli of ambulation and furosemide. Urinary PGE2 excretion was higher in NREH than in CG (p less than 0.05) while LREH showed values lower than in CG (p less than 0.001). Plasma aldosterone levels were similar in the three groups. In CG and EH patients PRA and urinary PGE2 were closely related (CG r = 0.516, p less than 0.05, EH patients r = 0.674, p less than 0.001). Indomethacin administration induced a decrease of PGE2 in both CG (n = 8) and NREH (n = 8) (p less than 0.01). In contrast, indomethacin induced no changes in PGE2 excretion of LREH (n = 5). Furthermore in the group of patients with NREH indomethacin induced a significant increase in blood pressure (p less than 0.01) and body weight (p less than 0.01) while glomerular filtration rate, 24 hour natriuresis PRA and plasma aldosterone decreased (p less than 0.01). On the contrary, in LREH indomethacin did not alter any of the parameters measured. These results indicate that LREH and NREH may be regarded as two different populations distinguishable not only by different secretion of PRA but also by different excretion of PGE2 in urine and by their characteristic response to indomethacin.

Interference by ranitidine with aldosterone secretion in vivo

SummaryThe effect of a 3-day oral course of ranitidine on plasma aldosterone level has been studied in 6 normotensive volunteers maintained in a state of sodium depletion. A significant fall in plasma aldosterone (p<0.05–0.02), in both the overnight recumbency levels and in the levels obtained during a two hour period of ambulation was observed. The change took place in the absence of variation in plasma renin activity and potassium. Plasma cortisol and prolactin levels were lower after ranitidine at the beginning of the test but their values were not significantly different after ambulation during ranitidine therapy. Ranitidine appears to interfere with aldosterone secretion in vivo.

Diuretic and natriuretic properties of fenoldopam in chronic renal failure.

The effect of intravenously administered fenoldopam on diuresis and natriuresis was investigated in a group of 10 patients with advanced chronic renal failure. After an initial basal period of 1 h, a fenoldopam infusion was started and maintained for 12 h at rates varying between 0.025 and 0.1 microgram/kg per min. During the study, blood pressure was measured every 10 min and urine volume, natriuresis and creatinine clearance were measured hourly. Fenoldopam induced a significant increase in urine volume, natriuresis and creatinine clearance (P less than 0.05-0.001) accompanied by a small but significant drop in blood pressure (P less than 0.05-0.01). These results show that for advanced chronic renal failure, fenoldopam has diuretic and natriuretic properties that could be of clinical relevance.