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Biomedical subjects

V Kerlan

Publications and source records attributed to V Kerlan.

17 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

Ocular naevus and melanoma in acromegaly.

Acromegaly favours the development of extrapituitary neoplasms presumably promoted through increased GH and IGF-I levels. We describe here two patients which acromegaly and benign and malignant melanocytic tumours of the eye choroid. The first patient had a 15 year history of progressive acromegaly despite trans-sphenoidal surgery, radiation and bromocriptine therapy when she presented with melanoma of the eye and a contralateral benign melanocytic tumour. The second patient was referred with typical acromegaly. The initial fundal examination revealed a right sided benign melanocytic tumour of the choroid. Subsequent follow up of the naevi has not shown any change in the tumours after one and three years respectively. The occurrence of melanoma has not been reported in acromegaly. Increased growth of benign naevi might be expected as GH and IGF-I receptors have been described on melanocytes. As naevi may degenerate into melanomas in normal subjects and radiation therapy could trigger their transformation, we suggest that prior to irradiation, acromegalic subjects should undergo a careful ocular examination in order to assess the presence of ocular naevi.

Acromegaly

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

[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

[Pregnancy: a way of recovering from prolactin-secreting adenoma? 18 cases].

Fifteen patients with prolactin-secreting pituitary adenoma completed a total of 18 pregnancies. Changes in blood prolactin levels and computerized tomographic images of the pituitary gland were studied. No increase in size of the adenoma was observed, and in 2 cases the tumour was found to be necrotic in the post-partum period. In all patients the prolactinaemia significantly decreased immediately after delivery. Thus, by inducing partial necrosis of the adenoma pregnancy may result in post-partum reduction of blood prolactin levels.

Adult

Leydig cell tumor with gynecomastia: further studies--the recovery after unilateral orchidectomy.

The recovery of exocrine and endocrine testicular function was studied in six patients orchidectomized for an estrogen-producing Leydig cell tumor. Gynecomastia disappeared in four patients. The contralateral testis, whose volume was reduced, returned to normal size after 30 days. Sperm density returned to normal in only one of the four patients in whom the preoperative sperm count was reduced. One day after unilateral orchidectomy, plasma estradiol decreased to normal and testosterone (T) fell about 50%. On the 10th postoperative day, plasma T [5.60 +/- 1.20 ng/ml (SD)] was normal. On day 120, T was higher than on day 10 (6.83 +/- 1.20 ng/ml). There was no significant increase of T after a single injection of hCG (5000 IU) on day 10, and the T response was similar to that of normal men on day 120. Plasma FSH and LH were increased on the 10th postoperative day; they then decreased between 60 and 120 days after the operation but were still above the normal values on day 120. The FSH/LH ratio, which was 0.43 +/- 0.17 preoperatively returned to normal (1.60 +/- 0.25) 10 days postoperatively. In conclusion, after hemicastration for an estrogen-secreting tumor, testicular hormonal secretion returns to normal within 120 days but spermatogenesis may still be impaired at this time.

17-alpha-Hydroxyprogesterone

[Estrogen-progestogen agents and megaloblastic anemia].

TwO cases of megaloblastic anaemia, of which one was very severe, occurring in women who had been taking oestrogen-progestogen oral contraception over a long period of time, are reported. The authors take the opportunity, after having reviewed the literature, of pointing out the role of oestro-progestogen products in bringing about vitamin deficiencies. They discuss how and where oestrogen-progestogen products work on folic metabolism and emphasize that there is an associated factor which starts off the deficiencies.

Adult

[Evolution of levels of free thyroxine and thyrotropin in treated Cushing disease].

OBJECTIVE: Determine the frequency and changes in thyroid hormones in Cushing's disease. METHODS: Free thyroxin and thyrotropin levels were measured in 11 patients (age range 17 to 60 years) with Cushing's disease both before and after resection of the pituitary adenoma. RESULTS: Free thyroxin levels were low (8.3 to 11.7 pmol/l) in 7 patients. These patients had no clinical manifestations of hypothyroidism. In 4 patients, cure of the pituitary adenoma led to normalization of the thyroid hormones 10 days after operation (13 to 55 pmol/l); in the other cases surgical cure was unsuccessful and thyroxin levels remained low. Cortisol levels were finally normalized in these patients after irradiation of the pituitary, a second pituitary operation, or bilateral resection of the adrenal glands in 2 patients. Normal thyroxin levels were thus achieved. There was no correlation between serum cortisol and free thyroxin. CONCLUSION: Thyroid hormones should be assayed regularly in patients with Cushing's disease as a supplementary control of treatment effectiveness.

Adolescent