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Biomedical subjects

P Vecsei

Publications and source records attributed to P Vecsei.

At least 91 records · Page 5Linked to original sources

Aldosterone metabolites and possible aldosterone precursors in hypertension.

The value of the urine tests: free aldosterone, aldosterone-18-glucuronide, tetrahydroaldosterone 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone in distinguishing primary aldosteronism from essential hypertension was studied in patients with typical and atypical primary aldosteronism and in patients with essential hypertension. The discriminating function of the tetrahydroaldosterone determination was the best, followed by 18-hydroxycorticosterone, free aldosterone and aldosterone-18-glucuronide. The measurement of 18-hydroxydeoxycorticosterone was without distinguishing value. Three cases with hypertension, adrenal adenoma, elevated 18-hydroxycorticosterone but normal aldosterone values were observed. In longitudinal studies the excretions of aldosterone, aldosterone metabolites and possible precursors periodically varied independently of each other. Determinations of urine aldosterone, aldosterone metabolites, 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone were not applicable for differential diagnosis of the adenoma and hyperplasia forms of primary aldosteronism.

Adenoma↗

Urinary free 18-hydroxycorticosterone, plasma aldosterone, and urinary aldosterone metabolites in normal pregnancy.

The final steps in aldosterone biosynthesis are unclear. Undecided is whether 18-hydroxycorticosterone is a precursor of aldosterone or an end product. 18-Hydroxycorticosterone is secreted in close relationship to aldosterone. To get adequate information on the status of aldosterone in pregnancy, determination of more than one parameter of aldosterone seems to be necessary. Urinary excretion of free 18-hydroxycorticosterone, tetrahydroaldosterone, aldosterone-18-glucuronide, free aldosterone, and the plasma concentration of aldosterone were measured by radioimmunoassay in 16 primigravid women in the last trimester of normal pregnancy and in 13 healthy nonpregnant women. All steroids measured were significantly increased in pregnancy. The ratios of aldosterone-18-glucuronide to tetrahydroaldosterone in the two groups were not significantly different, so that significant changes in renal or hepatic aldosterone metabolism could not be demonstrated in pregnancy. When pregnant women with ankle edema (n = 7) were compared to pregnant women without edema (n = 9), no differences in steroid patterns could be found. The increased excretion of 18-hydroxycorticosterone in pregnancy confirms the state of hyperaldosteronism in normal pregnancy which is associated with an increase in biologically active, free aldosterone. Dissociation in the excretion of the two aldosterone metabolites and free aldosterone was found in three pregnant women, in whom excretion of aldosterone-18-glucuronide was increased but excretion of tetrahydroaldosterone and free aldosterone was in the normal nonpregnant range.

18-Hydroxycorticosterone↗

Characterisation of aldosterone metabolites cross reacting with aldosterone and tetrahydroaldosterone antibodies.

Metabolites of aldosterone were extracted from human urine collected over three days following the intravenous injection of a tracer dose of tritium labelled hormone. After enzymic hydrolysis, steroids were separated by column, paper and thin-layer chromatography and the polarities of the labelled metabolites were compared with the chromatographic properties of known aldosterone products. The pattern of metabolites changed over the three days, from that associated with typical aldosterone metabolites, to less polar metabolites. Materials in the organic extract from a pH-1 hydrolysate of pooled pregnancy urine, were located by their ability to bind with aldosterone and tetrahydroaldosterone antisera and exhibited similar chromatographic properties to the radioactive metabolites. Using GC-MS, the identity of this immunoactive material could not be established in extracts after purification from 200 ml pregnancy urine but some synthetic derivatives of aldosterone as candidate compounds, were excluded.

Adrenal Cortex Neoplasms↗

Met-enkephalin inhibits mineralocorticoid production in isolated human aldosteronoma cells.

In vitro application of the morphinomimetic met-enkephalin resulted in inhibition of mineralocorticoid production by aldosterone-producing adenomas. Aldosterone, deoxycorticosterone, and corticosterone production by adrenocortical cells isolated from aldosteronomas has been studied under basal conditions and after stimulation with ACTH-(1-24). The blocking effect of met-enkephalin on the rate of aldosterone, deoxycorticosterone, and corticosterone release was significant at a concentration as low as 10(-11) M (P less than 0.001, P less than 0.01, and P less than 0.001, respectively). Dose-dependent inhibition of steroid biosynthesis became more apparent with increasing amounts of met-enkephalin in the incubation medium (10(-11)-10(-5) M); at a concentration of 10(-5) M, met-enkephalin decreased the production of aldosterone by 45%, that of deoxycorticosterone by 51%, and that of corticosterone by 44%. Increased steroid biosynthesis stimulated by ACTH-(1-24) was also significantly blocked by met-enkephalin. In a concentration of 10(-5) M, met-enkephalin produced significant decreases in aldosterone (P less than 0.001), deoxycorticosterone (P less than 0.05), and corticosterone (P less than 0.001) production compared to the peak values obtained after stimulation with 0.85 X 10(-10) M ACTH-(1-24). These data allow us to conclude that the inhibitory effect of met-enkephalin on mineralocorticoid production exerted at the level of the adrenals might be complementary to the factor(s) thought to be involved in the regulation of adrenal steroid production, playing a role similar to that of the biogenic amines originating in the adrenal medulla and regulating the adrenal cortex by a peripheral neurohumoral paracrine mechanism.

Adenoma↗

Circadian rhythm of serum progesterone levels in human pregnancy and its relation to the rhythm of cortisol.

Progesterone and cortisol were measured in the peripheral blood of pregnant women using radioimmunoassay. Ten women were between 18 and 25 weeks of pregnancy and 10 were between 32 and 38 weeks of pregnancy. Blood for the hormone determinations was drawn at hourly intervals. A significant circadian progesterone rhythm was found with the nadir at 8.00 h and the peak around midnight. The progesterone rhythm showed a significant inverse relation to the cortisol rhythm (tau = 0.310). No difference was detected between the two groups for progesterone rhythm or its inverse relation to the cortisol rhythm.

Circadian Rhythm↗

Increased excretion of 18-hydroxycorticosterone in patients with adrenal adenomas and hypertension.

Two female patients, 54 and 34 years old, each presented with an adrenal adenoma and hypertension. Blood pressure fell after removal of the tumors. The first patient had high urinary 18-hydroxycorticosterone and periodically elevated 18-hydroxy-deoxycorticosterone excretions. The second patient had elevated 18-hydroxycorticosterone and free cortisol excretions. Urinary aldosterone, aldosterone metabolites and plasma aldosterone were not increased. Plasma renin activity was suppressed and serum potassium levels were normal. After surgery, no elevated steroid values were found. Elevated 18-hydroxycorticosterone excretion may be an indicator of yet unknown hypertensinogenic mechanisms. The role of 18-hydroxycorticosterone in the etiology of hypertension is still unknown.

18-Hydroxycorticosterone↗

[Radioimmunologic detection of triamcinolone-acetonide and its application in a study on the hydrolysis of water soluble corticoid esters].

The rate of hydrolysis of different water soluble esters of corticoids was determined with newly developed specific radioimmunoassays in healthy subjects. It can be found, that triamcinoloneacetonide phosphate was significantly faster transformed into free form after i.v. application than the reference substances prednisolone- and methylprednisolone hemisuccinate. Moreover the plasma concentration of free triamcinolone-acetonide decreases much faster than that of free prednisolone and methylprednisolone. This shows, that triamcinoloneacetonide is distributed wider and very quickly, probably in the intracellular fluid volume. At this time it is not clear, whether only free steroids are biologically active or the water soluble derivatives as well. Our results can be of clinical importance because of the different rates of hydrolysis as well as of differences in the diffusion.

Adrenal Cortex Hormones↗

Direct radioimmunoassays for "aldosterone" and "18-hydroxycorticosterone" in unprocessed urine, and their use in screening to distinguish primary aldosteronism from hypertension.

For distinguishing primary aldosteronism from essential hypertension, we use simple direct radioimmunoassays for "aldosterone" (aldosterone and other materials that react with the antibody to aldosterone) and "18-hydroxycorticosterone" (similarly) in unprocessed urine. Patients with primary aldosteronism have high values for "aldosterone." This diagnosis can be validated by assays of further urine samples from the same person and by additional direct assays for "18-hydroxycorticosterone." In none of 65 urine samples from 26 patients with primary aldosteronism were both "aldosterone" and "18-hydroxycorticosterone" values within their reference intervals. However, a few "aldosterone" and "18-hydroxycorticosterone" values for patients with essential hypertension and normal aldosterone excretion were also (moderately) increased. Thus, when high values are found, true aldosterone values must be estimated by extraction and chromatography, to eliminate false positives. The "aldosterone" and "18-hydroxycorticosterone" values by our procedure are much higher than the corresponding values for urinary free aldosterone and 18-hydroxycorticosterone. Although not identified, the immunoactive materials are probably metabolites of aldosterone and 18-hydroxycorticosterone.

18-Hydroxycorticosterone↗

[Plasma concentration and systemic effect of betamethasone after intra-articular injection (author's transl)].

Plasma concentrations of betamethasone, cortisol and corticosterone were measured before and after intraarticular injection of a betamethasone-depot preparation (Celestan-Depot) by radioimmuno-assay in 31 patients. Plasma concentration of betamethasone reached its maximum of between of 10 and 17 microgram/dl 30 min after injection. It had fallen to half after 2 hours, and practically to nil from the eighth day onwards. Lowest plasma levels of cortisol and corticosterone occurred after 6--24 hours, returning to the normal range after four days. In nine patients with knee-joint effusion and synovitis the plasma concentration of betamethasone was significantly higher after 24 hours, and cortisol and corticosterone values after 48 hours significantly more suppressed, than in patients without joint effusions and signs of inflammation. The results indicate that plasma concentration of betamethasone and the suppressant effect on the adrenal cortex after intra-articular injection is similar to that after intramuscular applications. Correspondingly, systemic application of the cortisol derivatives can cause significant side effects and be contra-indicated also after intra-articular injection.

Adolescent↗

Parallelism of 11 beta- and 18-hydroxylation demonstrated by urinary free hormones in man.

To investigate whether the functions of 11 beta- and 18-hydroxylase are parallel in the human adrenal cortex, we measured urinary free deoxycorticosterone (DOC), free 18-hydroxy-DOC (18-OH-DOC), and free corticosterone (B) in 22 subjects (aged 3 6/12 to 19 yr) before and after metyrapone administration and ACTH infusion. The substrate to product ratio was used as an index of enzyme activity. There were parallel changes in the ratios of DOC to B (11 beta-hydroxylase) and DOC to 18-OH-DOC (18-hydroxylase) in all conditions, while the B to 18-OH-DOC ratio (product ratio) was relatively constant. The correlations between the ratios of DOC to B and DOC to 18-OH-DOC as well as between B and 18-OH-DOC were highly significant under all conditions (r = 0.89; P = 0.00001). These findings are consistent with previous in vitro studies and studies in patients with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency, suggesting that a single enzyme system is responsible for both 11 beta- and 18-hydroxylation of DOC in the adrenal zona fasciculata. As part of the metyrapone study, 18-OH-B was measured: 18-OH-B values decreased significantly, and the B to 18-OH-B ratio increased during metyrapone administration (from 0.38 +/- 0.09 to 1.79 +/- 0.04; P < 0.005), showing inhibition of 18-hydroxylation of B as well. Since 18-OH-B was suppressed without a decrease in PRA, we concluded that this inhibition is a primary metyrapone effect and not the result of increased DOC and suppressed PRA.

18-Hydroxydesoxycorticosterone↗

Mineralocorticoids in the nephrotic syndrome of children.

Free aldosterone, the aldosterone precursor 18-OH-corticosterone, and 18-OH-deoxycorticosterone as well as the aldosterone metabolites 18-glucuronide and tetrahydroaldosterone were measured by radioimmunoassay in the urine of 24 children with the nephrotic syndrome. In addition renin activity, aldosterone and corticosterone were measured in plasma. All children with manifest edema showed increased values of one or more of the measured aldosterone parameters indicating hyperaldosteronism. In non-edematous patients one or more parameters were increased in 9 of 16 patients. Free aldosterone, tetrahydroaldosterone and 18-OH-corticosterone proved to be the most sensitive urinary parameters for the detection of increased mineralocorticoid function. Free urinary aldosterone was correlated with sodium excretion and with serum albumin. The pathogenesis of hyperaldosteronism in the nephrotic syndrome and its role in the development of edema are discussed.

Adolescent↗

Damage to testicular function in chronic renal failure of children.

The functional endocrine reserve of testes was studied in 58 boys before and during puberty at different stages of chronic renal failure. Plasma testosterone (T) and dihydro- T were measured before and seven days after stimulation with human chorionic gonadotrophin (HCG). The T response to HCG often appeared to be already subnormal in renal failure before puberty had started. A negative correlation was observed in prepubertal boys between serum creatinine and stimulated T levels before the start of dialysis. During puberty the response to HCG was lower in boys on conservative treatment and on haemodialysis than after transplantation.

Adolescent↗

Screening radioimmunoassay for aldosterone in preheated plasma without extraction and chromatography.

We directly estimated plasma aldosterone radioimmunologically with use of an antiserum raised against an aldosterone-3-oxime/bovine serum albumin conjugate, the estimation being on samples with and without heating (60 degrees C), and diluted and undiluted. Values so obtained were compared with those by radioimmunoassay after extraction and chromatography. The correlation--even negative values were obtained--was poorest when the steroid was directly estimated in nonheated, undiluted plasma. Correlations were best (r = 0.918) for preheated and diluted native plasma, and the interassay CV was 9.8% (n = 57). However, there were some extraordinarily high values. After equilibrium dialysis of native and preheated (60 degrees C) plasma (15 plasma samples), the percentages of apparent free aldosterone and cortisol increased from 51.4 +/- 2.6% (SEM) to 64.3 +/- 1.6% and from 11.5 +/- 2.2% to 61.1 +/- 1%, respectively. We conclude that aldosterone-binding proteins play a role in direct radioimmunoassays of aldosterone in plasma, but by heating (with or without diluting) the plasma, direct assay can be used as a simple, fast, and inexpensive screening method.

Aldosterone↗