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Biomedical subjects

J P Bercovici

Publications and source records attributed to J P Bercovici.

At least 19 recordsLinked to original sources

[Primary hyperaldosteronism and adenoma of the adrenal cortex. Suppression of aldosterone with dexamethasone].

The aim of the study was to evaluate dexamethazone test in a patient with primary aldosteronism caused by an adrenocortical adenoma. We observed a 50% decrease of plasma aldosterone as in glucocorticoid suppressible aldosteronism (GSA) but absolute value of aldosterone remained higher than 40 pg/ml. Basal plasma and urinary values of 18 OXO and 18 OH cortisol were not significantly elevated as in GSA. Inversely, the evaluation of 11 beta-hydroxylase activity of mineralocorticoids was in favor of a benign adrenal tumor.

Adenoma↗

[Cushing's disease: role of feeding].

We report a clinical case of a patient with corticotropin dependent Cushing disease. In this patient ingestion of mixed meals is followed by an increase of ACTH and cortisol. This effects seems secondary to ingestion of proteins, and it can be reproduced by intravenous injection of aminoacids. The pattern observed is similar to what is observed in normal subjects. Neurotransmitter substrate from protein meals or after intravenous injection of aminoacids may influence the factors controlling ACTH secretion in the studied patient.

Adrenocorticotropic Hormone↗

[Polycystic ovary and diazoxide. In vivo study].

The suppression of hyperinsulinism with diazoxide (300 mg/d during 30 days) in a young woman with PCOS and hirsutism, hyperinsulinism and insulinoresistance was followed by a modification of plasma androgens. Testosterone (T) and free testosterone (fT) were reduced after ten days and then increased but always remained below the baseline level. DHEAS had increased 200% by day 10, and 3 alpha-adiol G to three times its basal value by day 20. These modifications were constant during the treatment. fT decrease was secondary to reduction of hyperinsulinism which was followed by an increase of TeBG and a modest and transient reduction of androgen theca cells production. DHEAS increase was due to hyperinsulinism suppression which stimulated adrenal 17-20 lyase activity. 3 alpha-adiol G increase was concomittant, and can be considered as an index of adrenal androgen secretion.

Adolescent↗

Longitudinal study of maternal plasma bioavailable testosterone and androstanediol glucuronide levels during pregnancy.

OBJECTIVE: The aim of this study to evaluate during normal pregnancy plasma bioavailable testosterone and androstanediol glucuronide levels. MEASUREMENTS: Bioavailable testosterone, androstanediol glucuronide and SHBG levels were evaluated every 4 weeks from week 6 to week 38 in 10 normal pregnant women. We also measured plasma oestradiol, oestriol, delta 4-androstenedione, 17-hydroxyprogesterone, progesterone and testosterone. RESULTS: The mean bioavailable testosterone levels were within the range of non-pregnant women but with an increasing trend until delivery. Androstanediol glucuronide had increased at weeks 6 and 8, decreased at week 14, remained low at week 30, and increased again at week 34. SHBG was significantly correlated with testosterone, oestradiol and oestriol. No correlation could be established between androstanediol glucuronide and any other parameter. DISCUSSION: Bioavailable testosterone (non-SHBG bound testosterone) represents the sum of free testosterone plus albumin bound testosterone. The increase in testosterone concentrations with decreased albumin levels during pregnancy, could suggest reduced metabolic clearance of testosterone throughout pregnancy. No correlation was established between the decrease in androstanediol glucuronide and increase in progesterone, suggesting that the decrease in androstanediol glucuronide is not a consequence of the inhibitory effect of progesterone on 5 alpha-reductase activity.

17-alpha-Hydroxyprogesterone↗

[Mid-term and long-term outcome in Leydig cell estrogen tumors].

A study has been realized in six patients with estrogen secreting Leydig cell tumors from 18 to 120 months after hemicastration. Testicular contralateral volume is normalized, gynecomastia can be completely reduced, sex steroids are normalized while gonadotropins can be temporary increased. Spermogram which is abnormal can be normalized. These results confirm the heterogeneity of these tumors.

Adult↗

[Intracardiac ectopic thyroid].

Intracardiac ectopic thyroid tissue was removed in a 51 years old woman, after echography has discovered a tumor in the right ventricle. There was a normal thyroid gland in the neck and thyroid function tests were normal. Intra-cardiac ectopic thyroid tissue is very rare; it is due to an abnormality of embryological development, when thyroid anlage is in close contact with the embryonic heart.

Cardiomyopathies↗

Nature of cytochromes P450 involved in the 2-/4-hydroxylations of estradiol in human liver microsomes.

Kinetics of the 2- and 4-hydroxylations of estradiol (E2) by human liver microsomal samples were studied to determine the major P450 isoform involved in these endogenous reactions. Thirty human liver microsomal samples were analysed. Metabolism of 25 microM [14C]E2 produced 2-hydroxy and 4-hydroxy derivatives with a ratio of 3.2 +/- 1.5 and a great inter-individual variation. Kinetic analysis of the 2- and 4-hydroxylations of E2 exhibited a curvilinear double reciprocal plot with an apparent Km of 15 microM. Further experiments demonstrated that alpha-naphthoflavone, testosterone and progesterone increased the 2-hydroxylation activity, suggesting the involvement of a substrate activation mechanism. These two hydroxylations of E2 were shown to be catalysed by cytochrome P450 with an apparent dissociation constant Ks of 0.8 microM. These 2- and 4-hydroxylations inter-correlated significantly (r = 0.93; N = 30). The 2-hydroxylation of E2 correlated with four monooxygenase activities known to be supported by P450 3A4/3A5, namely nifedipine oxidation (r = 0.78; N = 29); erythromycin N-demethylation (r = 0.69; N = 27), testosterone 6 beta-hydroxylation (r = 0.66; N = 25) and tamoxifen N-demethylation (r = 0.64; N = 29). On the other hand, E2-hydroxylations did not correlate with activities supported by P450 1A2 and P450 2E1. Furthermore, drugs as cyclosporin, diltiazem, triacetyl-oleandomycin and 17 alpha-ethynylestradiol inhibited more than 90% of the E2-hydroxylations at concentrations < 250 microM, while weak inhibition was shown with 500 microM cimetidine and no significant inhibition with caffeine, phenacetin and omeprazole. Finally, 2- and 4-hydroxylations of E2 correlated significantly with the content of P450 3A4/3A5 immunodetected by a monoclonal antibody anti-human P450-nifedipine (r = 0.84; N = 28). E2-hydroxylation activities were inhibited by more than 80% with polyclonal anti-human anti-P450-nifedipine. Preincubation of human liver microsomes with 100 microM gestodene (a suicide substrate of P450 3A4) inactivated this P450 isoform and accordingly allowed evaluation of the contribution of other P450 isoforms to the E2 metabolism to about 21% (+/- 17%, N = 29). All these results taken together suggest that P450 3A4/3A5 are the major forms involved in the formation of catecholestrogens in the human liver microsomes.

Adolescent↗

[Serologically detected HY antigen and its regulation].

The serologically detected, male predominant s HY Ag is a surface glycoprotein. The structural gene would be located on the 6th chromosome and regulated by gonosomal genes. The presence of testes (or testicular remenants) is linked to the s HY antigen expression in most abnormalities of sexual differentiation. However, the basal s HY Ag value is sometimes increased in the absence of any testicular tissue, as in virilized females (21-hydroxylase deficiency, idiopathic or ovarian hirsutism). Homogametic sex s HY Ag may increase to heterogametic sex values under the action of androgens in mammals and that of oestrogens in birds.

Female↗

Oestrogen secreting Leydig cell tumour and GnRH agonist in-vivo and in-vitro studies.

OBJECTIVE: The purposes of our study concerning two patients with oestrogen secreting Leydig cell tumour were to determine whether endogenous LH levels are involved in testicular tumour steroidogenesis and whether aromatase activity of oestrogen secreting Leydig cell tumours is directly or indirectly dependent on LH levels. MEASUREMENTS: E2 and T were evaluated after hCG injection (5000 IU) during 96 hours. Bio and immuno LH, T, E2, were determined at the basal state and after administration of D-Trp-6-GnRH agonist (3.75 mg) every 3 weeks. The abnormal testis was removed after the third injection and testicular venous blood was collected during the operation. Testicular tumour was incubated with 4-14C-T. RESULTS: Oestradiol (E2) response to hCG injection (5000 IU) was prolonged and exaggerated while that of testosterone (T) was similar to that of the controls. The aromatase index (E2/T) remained elevated even 96 hours after hCG. Intramuscular injection of the GnRH agonist, D-Trp-6-GnRH (3.75 mg) resulted in a reduction of immunoreactive and bioactive LH. T was decreased to about 10% of baseline levels and E2 fell from 240 to 36 pmol/l. In the blood of the spermatic veins collected in the course of surgery, E2 levels were found to be lower in comparison with the controls. E2 was found to be twofold higher in the spermatic vein draining the tumoral side than in that of the contralateral testis. Incubation of the testicular tumours with 4-14C-T, displayed a reduced aromatase activity (conversion of T to E2: 0.3 and 0.1% in patients 1 and 2 respectively). CONCLUSIONS: The kinetics of E2 response to hCG administration would suggest a modification of the regulation of the aromatase activity in this type of oestrogen secreting tumour. A certain endogenous LH level may be necessary to supply a sufficient quantity of T substrate, and to maintain aromatase activity of such Leydig cell tumours secreting oestrogens. These tumours seem to be responsive to endogenous LH levels.

Adult↗

Radioimmunoassay of plasma 21-deoxycortisol.

A reliable radioimmunoassay for the determination of plasma 21-deoxycortisol (21-DF) after chromatography on Sephadex LH20 columns of methylene chloride plasma extracts has been described and evaluated. The antiserum used was raised in rabbits injected with 21-DF-3-(O-carboxy-methyl)oxime-bovine serum albumin. In men (n = 10) the levels ranged from 0.11 to 0.29 ng/ml (mean +/- SD: 0.21 +/- 0.06). In women the mean levels were in the follicular phase: 0.16 +/- 0.06 (range: 0.05-0.22; n = 10) and in the luteal phase: 0.18 +/- 0.06 (range: 0.10-0.35; n = 12). No cyclical change and no significant difference between male and female groups were observed. In patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency very high levels were observed. The higher concentration of 21-DF found in adrenal effluent than in peripheral plasma has provided direct evidence of its adrenal origin in patients without 21-hydroxylase deficiency.

17-Hydroxycorticosteroids↗

[Long-term effects of treatment with SMS 201-995 on sleep apnea syndrome associated with acromegaly].

A 60-year-old woman with acromegaly associated with sleep apnea was treated with the somatostatin analogue SMS 201-995 (Sandoz) for several months. Growth hormone levels were normalized and a rapid improvement in sleep apnea was controlled with polygraphic nocturnal monitoring. Hypophysectomy seems to have variable effects on sleep apnea in acromegaly. The origin of obstructive apnea in acromegaly is therefore unclear.

Acromegaly↗

[Adrenoleukodystrophy in the child and adrenomyeloneuropathy. Study of 2 families].

Ten subjects from 2 families with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN), hereditary X-linked diseases, were systematically explored. We performed endocrinological, biochemical assays and neurophysiological tests; the latter consisted of nerve conductions (CNV), Hoffmann's reflex and multimodal evoked potentials: visual (flash and pattern, VEP), brainstem auditory (BAEP) and somesthetic (SEP) using median nerve stimulation at the wrist. We only considered values above 2 SD. The purpose of our study was to determine the correlation between neurophysiological and endocrinological perturbations and the presence of pathological traits. Our results suggest that the correlation is high in diseased male patients, lower for the ALD carriers (BAEP, SEP and CNV were more frequently abnormal) and very low for the AMN carriers. Only the biochemical assays appeared to have any value for the characterization of female carriers of ALD and AMN.

Adolescent↗

Increase in H-Y antigen-positive lymphocytes in hirsute women: effects of cyproterone acetate and estradiol treatment.

To investigate a possible relationship between lymphocyte H-Y antigen expression and plasma androgen concentrations in hirsute women, 27 hirsute women were studied. A significant increase in the percentage of H-Y-positive lymphocytes was found in both hirsute women with idiopathic hirsutism [13.4 +/- 2.9% (+/- SD); n = 15] and hirsute women with the polycystic ovary syndrome (13.0 +/- 2.8%; n = 12) compared to that in normal women (10.0 +/- 1.9%; n = 30; P less than 0.0005). Plasma testosterone and androstenedione concentrations, % H-Y+ lymphocytes, and hirsutism scores diminished during oral cyproterone acetate (50 mg/day) and percutaneous estradiol (3 mg/day) treatment. Significant correlations between % H-Y+ lymphocytes and hirsutism scores (P less than 0.001), % H-Y+ lymphocytes and plasma T concentrations (P less than 0.01) were found. We conclude that 1) women can produce H-Y antigen in the same way as men; 2) hirsutism is associated with an increase in H-Y antigen; and 3) the antiandrogen cyproterone acetate reduces H-Y antigen expression on lymphocytes.

Adult↗