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Biomedical subjects

G Brabant

Publications and source records attributed to G Brabant.

At least 181 records · Page 10Linked to original sources

[Dysthyroidism and fertility].

The role of the thyroid gland in sterility is not well known; hyperthyroidism may have an effect upon estrogen secretion by decreasing the level of the free forms of estradiol, resulting in a lowering or disappearance of the LH ovulatory peak. Clinically, severe hypothyroidism would cause a retarded sexual development but simple hypothyroidism and hyperthyroidism do not seem to have a major effect upon sexual maturity. During the period of genital activity, hyperthyroidism may result in amenorrhea and dysovulation phenomena reminding of ovarian dystrophy; hypothyroidism results in the same phenomena, with decreased libido, but with a better screening process and a better adjusted substitute treatment, these disorders are rare. Finally, systematic evaluation of the thyroid function in unexplained sterilities, appears unnecessary most of the time.

Female↗

Metabolism of the thyroid hormones.

This review covers the current knowledge about the various metabolic pathways involved in the conversion of thyroid hormones to the thyromimetically active and inactive iodothyronines. The concerted mechanism of systemic and local production of iodothyronines by tissue-specific iodothyronine deiodinase isozymes will ultimately determine the expression of thyroid hormone action. This is exemplified for the regulation of synthesis and release of TSH by iodothyronines at the pituitary level. Iodothyronine metabolites, e.g. Triac, rT3 and T3 amine may modulate TSH secretion, and alterations of local pituitary deiodination (e.g. iopanoate inhibition) influence diurnal TSH secretion without changing TRH-dependent episodic TSH secretion pattern. A summary of structure-activity relationships of greater than 200 naturally occurring and synthetic ligands of rat liver type I iodothyronine deiodinase isozyme propylthiouracil-sensitive) in vitro allows the design of iodothyronine analogues which either serve as specific substrates or antagonists of iodothyronine binding and metabolizing proteins. Furthermore, a complete picture of the ligand-complementary active site of the type I isozyme can be derived. A synthetic 'structurally optimized' iodothyronine-analogue flavonoid inhibitor of the type I deiodinase is able to displace T4 from binding to thyroxine-binding prealbumin and leads to unexpected organ-specific alterations of thyroid hormone metabolism and expression of thyroid hormone actions in an animal model. Therefore, for a complete understanding of thyroid hormone metabolism and action, thyroid hormone transport, cellular compartmentalization, and alternate pathways also have to be considered.

Pituitary Gland↗

Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration.

The inhibitory action of thyroid hormones (TH) and glucocorticoids on circadian and pulsatile TSH secretion was investigated in groups of five normal men by sampling blood every 10 min for 24 h (start, 1750 h). Serum TSH was measured by a sensitive immunoradiometric assay. Continuous infusion of 50 micrograms T3 or 250 micrograms T4 for 8 h (1900-0300 h) significantly suppressed serum TSH levels (T3, P less than 0.025; T4, P less than 0.05; by paired t test). Administration of 3 g sodium ipodate 7 h before TH infusion did not alter the TSH response to T3, but T4-dependent suppression was abolished. Pulsatile TSH secretion [basally, 5.8 +/- 1.3 (+/- SD) pulses/24 h, as analyzed by the PULSAR program; 6.8 +/- 1.9 by the Cluster program] was not significantly altered by any of the experimental conditions. The additional finding of blunting of the TSH response to TRH after TH alone or ipodate and T3 suggests a predominantly pituitary feedback action of TH exerted via conversion of T4 to T3. In contrast, bolus injections of 4 mg dexamethasone (dex) at 1900 and 2200 h abolished TSH pulses for at least 6 h (PULSAR, 6.6 +/- 1.6 pulses/24 h basally vs. 3.6 +/- 3.0 under dex; Cluster, 7.0 +/- 2.7 pulses/24 h basally vs. 1.6 +/- 1.6 under dex). Dex administration also resulted in a prompt, sustained, and significant suppression of basal TSH (P less than 0.0005). Together with a normal serum TSH response to TRH (in separate experiments 1, 9, and 19 h after dex administration), these data suggest that glucocorticoid feedback occurs at a suprapituitary level.

Adult↗

Hypertrophy and hyperplasia during goitre growth and involution in rats--separate bioeffects of TSH and iodine.

Goitre growth was investigated in rats receiving a low iodine diet (less than 0.1 microgram iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/1 T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 microgram T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 micrograms KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was highly significant correlation between goitre weight and TSH serum level (r = 0.93, P less than 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 micrograms KI/day (95 +/- 18 micrograms DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 +/- 21 micrograms DNA/gland) and under 0.5 microgram KI/day (161 +/- 19 micrograms DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.

Animals↗

Direct radioimmunoassay for human atrial natriuretic peptide (hANP) and its clinical evaluation.

A direct radioimmunoassay for the rapid and accurate detection of human ANP from unextracted plasma is described. The sensitivity was approximately 50 pg/ml, respectively 2.5 pg/tube, the intra-assay variation 4%, and the inter-assay variation less than 12%. Rat ANP (1-28, 5-25, 5-27 and 5-28), oxydized and reduced hANP as well as plasma samples from various patients run in parallel to the 1-28 hANP standard curve. These findings imply, that the antibody primarily recognizes the mid-region (amino acids 6-25) of the intact ANP, that the C-terminal portion further increases the immunoreactivity, and that circulating plasma hANP is reliably measured. Plasma hANP ranged from 50-166 pg/ml (mean +/- SD: 98.3 +/- 44.6) in healthy individuals, there was no significant difference between samples were drawn in upright or lying position, the apparent half-life of injected hANP was 5.65 minutes. Patients with liver cirrhosis revealed significantly higher hANP levels of 244.5 +/- 173.5 pg/ml. Patients with various forms of cardiac disease had hANP concentrations ranging from 50 to 1744 pg/ml, depending at least partially on the right atrial pressure. No difference was observed if the samples were drawn from either right or left intracardial locations. Our findings with this system demonstrate that hANP is reliably measured even without prior extraction.

Antibody Specificity↗

Pulsatile pattern of thyrotropin-release in normal men.

To evaluate the existence of a pulsatile secretion pattern of thyrotropin (TSH) the 24 h release profile of the hormone was investigated in 7 healthy male subjects by taking blood via an indwelling venous catheter at 10-min intervals. Thyrotropin levels were analysed with high precision by a recently developed immunoradiometric assay (IRMA) able to distinguish euthroid and hyperthyroid TSH-levels. Visual analysis (n = 10.4 peaks/24 h) and the computer assisted evaluation by the Santenprogramme (n = 9.9 peaks/24 h) as well as the Pulsar-programme (n = 7.7 peaks/24 h) revealed an episodic release pattern with a low amplitude of pulses. These preliminary results are highly suggestive of a pulsatile TSH secretion similar to other pituitary hormones.

Adult↗

Pulsatile gonadotropin-releasing hormone treatment in idiopathic delayed puberty.

Idiopathic delayed male puberty is defined as a delay of puberty beyond the age of 16, with prepubertal testosterone levels, normal gonadotropin responses to GnRH (excluding pituitary failure), and normal androgen responses to a single hCG injection (excluding testicular Leydig cell dysfunction), in absence of serious disease. Ten boys with this condition were evaluated as to their spontaneous LH, FSH, and PRL secretory patterns during a 24-h sampling period (20-min intervals). After this all patients were treated with pulsatile infusions of GnRH (25 ng/kg . pulse every 90 min for 10 days. Two groups could be distinguished by means of their pretreatment LH secretory pattern. Five patients had nighttime pulsatile elevation of LH levels, as usually occurs in early puberty. The other five patients did not have such a pattern (prepubertal type). The GnRH treatment resulted in increased LH and testosterone levels in both groups. All patients with pretreatment nighttime pulsatile LH secretion had steady pubertal development during the post-GnRH treatment observation period, whereas the other patients did not. In conclusion, among a number of tests, including chronic pulsatile GnRH treatment for 10 days, only the nocturnal LH secretory pattern differentiated delayed puberty from permanent hypothalamic hypogonadism in boys.

Adolescent↗

Thyrotropin--an episodically secreted hormone.

A recently developed highly sensitive immunoradiometric thyrotropin (TSH) assay capable to distinguish between euthyroid and hyperthyroid TSH-levels was used to evaluate the secretion-pattern of TSH in 10 healthy male subjects by taking blood via an indwelling venous catheter at 10 min intervals over 24 h. Visual analysis revealed a pulsatile pattern of hormone release with an average of 10.3 peaks/24 h. Evaluation by computer assisted programs such as the Santen-program (8.9 peaks/24 h, amplitude 0.60 mU TSH/l), the 'Pulsar'-program (6 peaks/24 h, amplitude 0.61 mU TSH/l) or power-spectrum analysis (11.9 peaks/24 h) showed similar results. These data suggest a pulsatile mechanism of TSH secretion similar to other pituitary hormones.

Adult↗

Human atrial natriuretic peptide (ANP) for the treatment of patients with liver cirrhosis and ascites.

The acute effects of human atrial natriuretic peptide (ANP) were investigated in 10 patients with liver cirrhosis and ascites. In all patients, diuresis and natriuresis were stimulated with a wide individual variation (50 to 500%) in response to a bolus injection of 30 micrograms ANP. No side effects of treatment were observed. Continuous infusion of ANP (300 micrograms/10 h/d) in a patient with liver cirrhosis and ascites, resistant to conservative forms of diuretic therapy, resulted in an initial increase of diuresis and natriuresis which subsequently returned to pretreatment levels. After initiation of pulsatile nocturnal treatment (5 pulses of 30 micrograms ANP every 3 h), diuresis increased, leading to a persistent normalization of sodium and chloride excretion. The patient lost 8 kg of weight during 16 days of treatment. Out of 3 additional patients on the same therapeutic regime, only one experienced a weight loss of 5 kg due to increased natriuresis and chloruresis. The remaining 2 patients did not respond during 5 resp. 7 days of therapy.

Adult↗

[Hyperprolactinemia and prolactinomas. Results of surgical and drug therapy].

185 patients with hyperprolactinaemia and prolactinoma were evaluated in a retrospective investigation. 128 patients were treated surgically whereby the prolactin serum level in 47% of the macroprolactinoma and 60% of the microprolactinoma patients was normalised (prolactin less than 25 ng/ml, no radiological evidence of tumor). Of those patients in whom the operation was less successful, a normal prolactin level could be achieved in 77% by additional therapy with dopamine agonists. Of 57 patients handled exclusively with drugs, the prolactin level was normalised by dopamine agonists in 78%. A small number of patients from both groups did not show a satisfactory fall in the prolactin level despite the use of markedly higher doses of dopamine agonists. During dopamine agonist therapy progressive tumor enlargement was detected radiologically in a previously operated patient.

Adolescent↗

Preoperative localization of parathyroid tumours by high resolution sonography.

Because of the frequent topographically unusual localization of parathyroid tumours the intraoperative identification remains a problem to the surgeon. Therefore, the accuracy of the preoperative localization of the parathyroid glands was assessed in 17 patients with extrarenal hyperparathyroidism using high resolution sonography (Siemens RA 1 and Sonoline 8000 small parts scanner operating at 7.5 mHz/5 MHz). The clinically suspected diagnosis was supported by changes in calcium, phosphate and alkaline phosphatase levels without any signs of renal dysfunction and by elevated levels of PTH in the 44-68 hPTH radioimmunoassay. All patients subsequently underwent surgery and the preoperative sonographic diagnosis could be confirmed in 82% of the cases. The smallest adenoma visualized measured 0.8 X 0.8 cms. The only carcinoma in the study did not appear sonographically different to the adenomata. These preliminary results suggest that high resolution sonography may become a valuable aid in the surgical management of extrarenal hyperparathyroidism.

Adenoma↗