Biomedical subjects

P Vecsei

Publications and source records attributed to P Vecsei.

At least 73 records · Page 4Linked to original sources

PubMed1986

Serial dexamethasone suppression tests in psychiatric illness: Part III. The influence of intervening variables.

The effects of different intervening variables on dexamethasone suppression test (DST) results were evaluated in depressed, schizophrenic, and manic patients. There was a significant correlation between age and DST results in major depression. Some "isolated peaks" of DST nonsuppression were explained by low dexamethasone serum levels. In schizophrenic and manic patients, the dexamethasone concentrations increased to above the normal range during the study period. A significant negative correlation between dexamethasone concentrations and DST results was found in schizophrenia and mania, but not in depression. Dexamethasone levels were generally higher in men than in women. Weight loss and hospital admission affected the DST in individual cases, whereas length of episode and drug withdrawal did not. Thus, the intervening variables accounted for some of the abnormal DST results, but other factors such as severity of illness, nonspecific stress, or possibly depression itself emerged as the main causes of abnormal DST results.

Adolescent↗

PubMed1986

[Pharmacokinetics of fluocortolone in long term therapy of patients with rheumatic and hematologic diseases].

The pharmacokinetics of fluocortolone (Ultralan oral) and its effect on plasma cortisol levels were investigated during long-term treatment of patients with rheumatic and haematological diseases with different doses of fluocortolone. Fluocortolone was administered in the morning and plasma levels of fluocortolone and cortisol were measured in samples obtained 1.5, 3, 4, and 5 h p. adm. by means of specific radioimmunoassays. Maximum concentrations of fluocortolone in plasma (Cmax) and areas under the fluocortolone plasma level curves (AUC) increased linearly with the dose. The peak time (tmax = 2.04 +/- 0.85 h) and the plasma half-life (t1/2 = 1.53 +/- 0.52 h) were independent of the dose administered. Cortisol suppression as indicated by morning cortisol levels below 50 ng/ml plasma was not observed with doses below 10 mg/d.

Adult↗

PubMed1986

[Nocturnal hypoglycemias and cortisol excretion in overnight urine].

In 20 juvenile diabetic inpatients the relationship between nocturnal hypoglycemia and overnight urinary cortisol excretion was studied. Cortisol was expressed as absolute quantity per kg body weight because the cortisol/creatinine ratio does not always yield reliable results in diabetic patients. Comparison between different patients yielded no significant difference between posthypoglycemic and non-posthypoglycemic cortisol values. Testing the difference between urinary cortisol excretion in posthypoglycemic and non-posthypoglycemic urine samples for every one of the patients intraindividually, however, a significant posthypoglycemic elevation was found. Posthypoglycemic cortisol response was irregular and variable not only in different patients, but also within the same patient. If a high excretion of cortisol is found in an overnight urine sample, it is very likely to be caused by nocturnal hypoglycemia. On the other hand it is impossible to exclude nocturnal hypoglycemia by normal urinary cortisol findings. Reactive hyperglycemia as described by Somogyi was seen only rarely in this study. It is concluded that even if a distortion by falsely high creatinine measurements in diabetics is ruled out, cortisol measurement in overnight urine samples cannot be used as easy routine method for the detection of nocturnal hypoglycemia.

Adolescent↗

PubMed1985

Clinical significance of unconjugated 3 alpha,5 beta-tetrahydroaldosterone and 5 beta-dihydroaldosterone measured by radioimmunoassay.

Radioimmunoassays of two unconjugated reduced metabolites of aldosterone were developed. Excretion rates of unconjugated 5 beta-dihydroaldosterone (5 beta-DHAld) and 3 alpha,5 beta-tetrahydroaldosterone (3 alpha,5 beta-THAld) were measured in 192 hypertensive patients and 16 normal subjects and results were compared with urinary tetrahydroaldosterone-glucuronide(TH-Aldo-glu), aldosterone-18-glucuronide (Aldo-18-glu) and 'free' aldosterone. Generally, values of unconjugated reduced metabolites correlated with one another but in some cases were exceptionally elevated indicating alteration of urinary bacterial flora or impairment of the enzymatic system regulating the conjugation reaction. We suggest that in those cases of hypertension and suspected primary aldosteronism when aldosterone-18-glucuronide and tetrahydroaldosterone glucuronide values remain within normal range, determination of the free metabolite fraction may be diagnostically helpful.

Aldosterone↗

PubMed1985

21-Deoxytetrahydroaldosterone excretion in primary hyperaldosteronism.

In earlier studies by our group it was shown that the urinary tetrahydroaldosterone excretion is a more reliable test for the diagnosis of primary aldosteronism than aldosterone-18-glucuronide ('urinary aldosterone'). However, in several patients with primary aldosteronism even the tetrahydroaldosterone values remained in the normal range. As the possible cause for this observation, the role of intestinal bacteria was considered which may transform tetrahydroaldosterone into 21-deoxytetrahydroaldosterone. Using a 21-deoxytetrahydroaldosterone radioimmunoassay, this hypothesis could be confirmed. The sums of the urinary 21-deoxytetrahydroaldosterone and tetrahydroaldosterone excretions revealed to be of better diagnostic value than the tetrahydroaldosterone values alone.

Adenoma↗

PubMed1985

Combined 21- and 11 beta-hydroxylase deficiency in familial congenital adrenal hyperplasia.

Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Hyperplasia, Congenital↗

PubMed1985

The influence of dimetindene maleate on the endogenous hydrocortisone synthesis suppressing potency of betamethasone.

Plasma hydrocortisone (cortisol) levels in 7 healthy volunteers were measured following administration of 0.25 mg betamethasone or 0.25 mg betamethasone and 1 mg dimetindene maleate. The H1-receptor antagonist dimetindene maleate did not influence the hydrocortisone suppressing activity of betamethasone, which was proved by comparison with the published plasma hydrocortisone levels of 162 young healthy untreated volunteers.

Adult↗

PubMed1984

Time course of plasma corticosterone, 18-hydroxycorticosterone and aldosterone concentrations following CRF administration in the rat. A phase of corticosterone inhibition.

Synthetic ovine CRF (8 micrograms/rat) injected intravenously in nembutal anaesthetized rats increased not only plasma ACTH and corticosterone but also aldosterone and 18-hydroxycorticosterone concentrations. The maximum elevation occurred 30 min after oCRF administration. 2 h and 4 h after injection the hormone concentrations declined and after 6 h the corticosterone and 18-hydroxycorticosterone values were lower than the corresponding controls. At this time aldosterone remained slightly elevated and ACTH unchanged. 24 h after oCRF injection no difference between the control and oCRF treated animals were evident.

18-Hydroxycorticosterone↗

PubMed1984

[Primary hypoaldosteronism and secondary pseudo-hypoaldosteronism].

We observed a 23-year-old man with pronounced hyperkalemia (max. 6.8 mmol/l) and hyponatremia (min. 112 mmol/l), which had been existent for 3 years without complaint except a transitory psychorganic syndrome due to hyponatremia. Physical examination showed no abnormality except hypotension (blood pressure 100/70 mmHg). Renal function tests were normal. Fractional clearance of sodium was significantly increased (0.8%), whereas that of potassium was decreased (2.4%). Plasma renin activity was tripled and rose after furosemide. Plasma aldosterone was lowered and showed no rise after furosemide. Suppression of plasma renin and aldosterone by saline infusion was normal. Pressor dose of angiotensin II was increased (17,9 ng AT II/kg/min). Urinary excretion of aldosterone and its conjugates was below normal, and aldosterone precursors were within normal range. The findings were interpreted as selective primary hypoaldosteronism caused by corticosterone methyl oxidase defect type II. However, neither fludrocortisone (0.5 mg/day) nor sodium chloride (200 mmol/day) led to a normalization of sodium and potassium in plasma. Additional pseudohypoaldosteronism was thus assumed. Aldosterone infusion (3 mg in 1 h) decreased renal excretion of sodium; potassium excretion failed, however, to increase in contrast to its pattern in normal man. These findings resemble additional pseudohypo-aldosteronism of type II. After 8 weeks' application of additional 80 mmol sodium (as sodium bicarbonate) plasma sodium and potassium showed normal values under combined treatment with fludrocortisone (0.1 mg/day) and sodium bicarbonate (80 mmol/day). It is to be assumed that the patient suffers from a reduced aldosterone biosynthesis in the presence of an additional transitory secondary pseudohypoaldosteronism.

Adult↗

PubMed1984

Development of plasma 21-deoxycortisol radioimmunoassay and application to the diagnosis of patients with 21-hydroxylase deficiency.

Specific 21-deoxycortisol (21-DF) antiserum was raised in New Zealand white rabbits using a 21-DF-3,20-oxime-bovine serum albumin complex. Plasma radioimmunoassay of 21-DF was developed and used together with a radioimmunoassay of 17-hydroxyprogesterone (17-OH-P) for diagnosis of patients with 21-hydroxylase deficiency of congenital and postpubertal forms. The assays were performed in plasma extracts after isolation by paper chromatography. The response of plasma 21-DF and 17-OH-P to i.v. ACTH (25 IU) was studied in 15 adult controls and compared to 8 women with the late onset form of 21-hydroxylase deficiency and 23 women with idiopathic hirsutism. Normal 21-DF values for women were 6.9 +/- 3.6 ng/dl and for men 9.71 +/- 2.73 ng/dl. Newborn children (age: 3-10 days) had a value of 8.3 +/- 4.8 ng/dl. These values are definitely lower than the lowest value ever published. This is possibly due to the specificity of the antibody. During the menstrual cycle the 21-DF values did not change. The baseline and post-stimulated concentrations of hormone were similar in controls and women with hirsutism but were significantly higher in women with the late onset form of 21-hydroxylase deficiency. In the congenital form of 21-hydroxylase deficiency the 21-DF values (baseline) were high. In general, the 21-DF and 17-OH-P values have shown parallel changes. However, one case of 21-hydroxylase deficiency with elevated 21-DF but normal 17-OH-P was observed. The use of 21-DF for the diagnosis of 21-hydroxylase deficiency is suggested.

17-Hydroxycorticosteroids↗

PubMed1984

Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone secretion.

To determine the effect of CRF administration on in vivo mineralocorticoid release, we performed experiments in rats and in man. In man, plasma aldosterone and 18-hydroxycorticosterone levels increased following i.v. CRF injection. In sitting subjects, the response was greater than in supine subjects, indicating an influence of posture. In the rat, CRF-induced increases in corticosteroid levels were dose-related, the largest response being for corticosterone, followed by 18-hydroxycorticosterone and then by aldosterone. Thus synthetic ovine CRF stimulates not only glucocorticoid but also mineralocorticoid secretion from the adrenals.

18-Hydroxycorticosterone↗

PubMed1984

Cushing's disease associated with an intrasellar gangliocytoma producing corticotrophin-releasing factor.

A 58-year-old woman had Cushing's disease with elevated plasma adrenocorticotrophin and an intrasellar tumor. Light microscopy showed that the tumor was a gangliocytoma containing immunoreactive corticotrophin-releasing factor accompanied by pituitary corticotroph hyperplasia. Ultrastructural examination identified an intimate association and desmosomal attachments between interdigitating cell processes of neurons and corticotrophs. It is suggested that Cushing's disease was due to the effect of corticotrophin-releasing factor on corticotrophs; this case represents a syndrome supporting the concept that, in some patients, Cushing's disease may have a hypothalamic origin.

Corticotropin-Releasing Hormone↗

PubMed1984

The pharmacokinetics of fluocortolone and prednisolone after intravenous and oral administration.

The pharmacokinetics of fluocortolone and of prednisolone were examined following a single intravenous injection of 5 mg and oral administrations of 10 and 20 mg to five healthy male volunteers. After intravenous injection the plasma levels of fluocortolone decreased biexponentially with half-lives of 9 +/- 5 min and 1.3 +/- 0.3 h. Total plasma clearance of fluocortolone was calculated to be 7.0 +/- 1.5 ml/min/kg. Oral administrations of fluocortolone revealed maximum plasma levels of 86 +/- 12 ng/ml (10-mg dose) and 174 +/- 34 ng/ml (20-mg dose) after 1.4 +/- 0.2 h. Intravenously administered prednisolone was rapidly distributed (t 1/2 alpha = 5 +/- 3 min) but more slowly eliminated from plasma than fluocortolone (t1/2 beta = 3.1 +/- 0.8 h). Correspondingly a total plasma clearance of 2.2 +/- 0.2 ml/min/kg was calculated. Oral administrations revealed maximum prednisolone plasma levels of 172 +/- 25 ng/ml (10-mg dose) and 278 ng/ml (20-mg dose) after 1.6 +/- 0.7 h. The absolute bioavailability of both corticosteroids was higher than 80% and independent of both dose levels investigated.

Administration, Oral↗

PubMed1984

Plasma dexamethasone concentrations and differential suppression response of cortisol and corticosterone in depressives and controls.

After a dexamethasone suppression test (DST), cortisol, corticosterone, and the test substance were determined by a direct radioimmunoassay in 42 samples obtained from 22 depressed patients and 8 controls. The DST results of both glucocorticoids agreed in most of the tests. In all seven cases with elevated but not definitely abnormal post-DST (1600 hr) cortisol levels (transitional range 30-50 ng/ml) the concurrent determination of corticosterone indicated that this corticosteroid may serve as a potent additional discriminator. Dexamethasone plasma concentrations at 1600 hr after a 1-mg test dose of dexamethasone at 2300 hr were significantly (p less than 0.01) lower in cortisol and corticosterone nonsuppressors than in suppressors. Since these data were obtained 17 hr after ingestion of dexamethasone (half-life 3.5-5 hr) any conclusions about an inverse correlation between dexamethasone and corticosteroid plasma concentrations would be speculative. However, the dexamethasone pharmacokinetics might be an important variable and may contribute to some of the recent uncertainty about the DST.

Adult↗

PubMed1984

[Renal acid excretion and renal molar load in healthy children and adults].

The urinary excretion of the quantitatively prevalent ions and nonionic solutes and of aldosterone-18-glucuronide was investigated in 49 healthy children and 22 healthy adults living at home. The median of renal net-acid-excretion was 0.99 meq/kg/day or 48 meq/day/1.73 m2 in children, and 0.75 meq/kg/day or 50 meq/day/1.73 m2 in adults. The median of osmolar load was 12.8 mosmol/kg/day or 643 mosmol/day/1.73 m2 in children, and 10.6 mosmol/kg/day or 661 mosmol/day/1.73 m2 in adults. High urinary osmolality was more frequently observed in children than in adults. The data may define a desirable range of renal net-acid-excretion (0.5-1.5 meq/kg/day) in children receiving synthetic diets.

Acid-Base Equilibrium↗

PubMed1983

Pineal modulation of ACTH 1-17 effect upon murine corticosterone production.

In tests of corticosterone production in vitro, aqueous pineal homogenate (APH) modulates the effect of a short-chain ACTH analogue, ACTH 1-17, added to adrenals from different circadian stages. Adrenal and pineal glands from female B6D2F1 mice, standardized on staggered LD 12:12 regimens, were obtained at the same clock-hour from each room, in order to cover 6 different circadian stages. Adrenals from each circadian stage were bisected and incubated with APH from the same circadian stage (isophasic incubation) or from one of the other 5 circadian stages (heterophasic incubation). ACTH 1-17 (0.05 IU) was added to each incubation medium. After 4 hours of incubation at 37 degrees C with 95% O2 and 5% CO2, the media were stored at -20 degrees C until corticosterone RIA were done. APH was found to have a statistically significant modulatory effect upon the stimulation by ACTH 1-17 of adrenal corticosterone production in vitro. This APH effect changed rhythmically as a function of circadian stage from amplification over no effect to attenuation, as a so-called feed-sideward.

Adrenal Glands↗

PubMed1983

Circadian pineal modulation of pituitary effect on murine corticosterone in vitro.

An old controversy is resolved as a novel effect: In a rhythmic fashion, aqueous pineal homogenate (APH) enhances, attenuates or leaves unaffected the production of corticosterone by mouse adrenals incubated with pituitary media. All glands stem from the same circadian stage in these (isophasic) studies on 72 female CD2F1 mice, standardized for two weeks in L 0600-1800 and D 1800-0600. Every 4 hours during a 24-hour span, 12 mice were killed. Pineals were removed for the preparation of APH and stored at 4 degrees C. Hypothalami, pituitaries and adrenals were removed, bisected and placed in wells containing 1 ml Krebs-Ringer buffer (K), at 4 degrees C, until incubation. At each circadian stage, bisected adrenals were incubated with 95% O2 and 5% CO2 at 37 +/- 1 degree C for 5 hours, with K only or with the addition of 0.05 IU ACTH 1-17 or APH or with isophasic pituitary or hypothalamic preincubation media with and without APH or muscle. Media were stored at -20 degrees C until corticosterone RIA. A circadian rhythm (p less than 0.05) characterized corticosterone production after stimulation by the pituitary alone or with APH. The overall modulatory effect of APH is an increased circadian amplitude of adrenal corticosterone production, in response to the isophasic pituitary.

Adrenal Glands↗

PubMed1983

Effect of cytotoxic drugs on the function of the hypothalamo-pituitary-adrenal axis.

We measured the serum concentration of thyroid-stimulating hormone (TSH), its response to exogenic TSH-releasing hormone (TRH), as well as cortisol plasma levels before and after stimulation with adrenocorticotrophic hormone in 15 patients before, during and after a chemotherapeutic cycle. 3/6 patients receiving only cytotoxic drugs developed a marked suppression of the TSH response to TRH and 1 of these patients showed an impairment of the adrenal function under chemotherapy. This was also observed in 7/9 patients receiving both cytotoxic drugs and corticosteroids; however, the individual pattern of the impairment was quite variable. 5/9 patients in this group developed a suppression of the TSH response to TRH. Impairment of the hypothalamo-pituitary-adrenal axis function under cytotoxic drugs and/or corticosteroids occurs with great variability and the mechanisms involved in its etiology are not yet fully understood.

Adrenocorticotropic Hormone↗