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Biomedical subjects

G Schaison

Publications and source records attributed to G Schaison.

At least 37 records · Page 2Linked to original sources
PubMed1999

Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin.

OBJECTIVE: Functional hypothalamic amenorrhoea (FHA) is a consequence of low dietary intake as observed in two major pathophysiological conditions, anorexia nervosa and/or intensive physical exercise. The aim of the present study was to assess in women with FHA and normal body mass index (BMI) and apparently normal daily activities, the degree of impairment of GnRH secretion, its nutritional origin and its reversibility. PATIENTS: Twelve women (22-35 years) with FHA not related with exercise and 12 age and BMI matched menstruating controls (NC) were studied. Six women with congenital hypothalamic hypogonadism (CHH), representative of complete gonadotrophin deficiency, were also enrolled for comparison. DESIGN: Plasma oestradiol (E2) and androstenedione (A) levels were measured and the pulsatile profile of LH was studied. A GnRH agonist test, using 100 micrograms S/C of DTrp6 GnRH (Triptorelin) was performed (sampling every 2 h for 24 h). Dietary intake, body composition and nutritional markers (FT3, ferritin, retinol binding protein (RBP), SHBG, IGF-1 and leptin) were measured. All the women with FHA were advised to normalize their diet during four months. The same studies were performed if nutritional markers and body composition were normalized. RESULTS: In FHA, mean plasma E2 and A levels were low. LH pulse frequency and amplitude were significantly reduced compared to NC (P < 0.005). FSH/LH ratio increased rapidly after triptorelin with a significant increase in plasma E2 levels between 18 and 24 h. In contrast, no response to triptorelin was observed in women with CHH. The fat body mass was lower and the lean body mass higher in FHA than in NC. Marked differences in nutritional intake were identified, with altered dietary composition. FHA consumed significantly less fat (P < 0.001) and less carbohydrate (P = NS) than the BMI-matched controls. Mean plasma levels of SHBG were increased whereas mean plasma levels of FT3, ferritin, RBP, IGF-1, and leptin were significantly decreased. Only three patients with FHA kept a balanced diet and improved their body composition after 4 months. LH pulsatile profile and response to triptorelin challenge were normalized in these patients. CONCLUSION: Mild dieting, close to normal but prolonged and characterized by an important fat restriction, is able to interfere with gonadotrophin secretion. Assessment of nutritional markers allows recognition of mild nutritional insufficiency as a common cause of FHAs. The gonadotrophin deficiency is partial and may be reversible after improvement of nutritional intake and body composition.

Adult↗
PubMed1999

Autoantibodies interacting with purified native thyrotropin receptor.

Native thyrotropin receptor (TSHR) was purified by immunoaffinity chromatography from membrane extracts of stably transfected L cells. An ELISA test was devised to study anti-TSHR autoantibodies directly. Comparison of native TSHR with bacterially expressed, denatured TSHR showed that the latter was not recognized by the autoantibodies, suggesting that they bind to conformational epitopes only present on the native receptor. The use of deglycosylated TSHR and of purified receptor ectodomain (alpha-subunit) showed that the autoantibodies recognized only the protein backbone moiety of the receptor and that their epitopes were localized entirely in its ectodomain. Autoantibodies were detected in 45 of 48 subjects with untreated Graves' disease and in 26 of 47 healthy volunteers. The affinity for the receptor was similar in the two groups (Kd = 0.25-1 x 10-10 M) and the autoantibodies belonged to the IgG class in all cases. Although the concentration of autoantibodies was higher in Graves' disease patients (3.50 +/- 0.36 mg.L-1) than in control subjects (1.76 +/- 0.21) (mean +/- SEM), there was an overlap between the groups. Receptor-stimulating autoantibodies (TSAb) were studied by measuring cAMP synthesis in stably transfected HEK 293 cells. Their characteristics (recognition of alpha-subunit, of deglycosylated TSHR, nonrecognition of bacterially expressed denatured receptor) were similar to those of the antibodies detected by the ELISA test. TSAb were only found in individuals with Graves' disease. The ELISA test measures total anti-TSHR antibodies, whereas the test using adenylate cyclase stimulation measures antibodies that recognize specific epitopes involved in receptor activation. Our observations thus disprove the hypothesis according to which Graves' disease is related to the appearance of anti-TSHR antibodies not present in normal subjects. Actually, anti-TSHR antibodies exist in many euthyroid subjects, in some cases even at concentrations higher than those found in patients with Graves' disease. What distinguishes the latter from normal subjects is the existence of subpopulation(s) of antibodies directed against specific epitope(s) of the receptor involved in its activation.

Animals↗
PubMed1999

The antigonadotropic activity of a 19-nor-progesterone derivative is exerted both at the hypothalamic and pituitary levels in women.

We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function [McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 microg, i.v.), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-acting GnRH agonist administration. In women with FHA, pulsatile GnRH (20 microg s.c., every 90 min) was given for two cycles with or without NOMA (5 mg for 21 days). In all NC women, ovulation was suppressed by NOMA. Mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. In MCA, neither NOMA nor GnRH agonist modified multiple ovarian cysts on ultrasound or plasma E2, levels which remained elevated, ruling out a direct ovarian effect. In FHA, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle. Addition of NOMA prevented the increase of plasma E2, decreased the amplitude of LH pulses, and prevented ovulation. In view of this unexpected action of NOMA at the pituitary level, seven samples of normal human female pituitaries were tested for the presence of progesterone receptor (PR) using a double labeling immunocytochemical technique. The presence of PR was detected in the seven human pituitary tissues. In addition, PR was found to be expressed only in gonadotroph cells. In conclusion, NOMA, a 19-nor-P derivative, has a potent antigonadotropic activity exerted at the hypothalamic level, inhibiting ovulation in NC women. In women with FHA, NOMA decreased the gonadotropin stimulation induced by pulsatile GnRH administration. According to the presence of PR in gonadotroph cells of normal human pituitaries, 19-nor-progesterone derivatives may also act on the gonadotropin secretion at the pituitary level.

Adolescent↗
PubMed1999

The same molecular defects of the gonadotropin-releasing hormone receptor determine a variable degree of hypogonadism in affected kindred.

Detailed endocrinological studies were performed in the three affected kindred of a family carrying mutations of the GnRH receptor gene. All three were compound heterozygotes carrying on one allele the Arg262Gln mutation and on the other allele two mutations (Gln106Arg and Ser217Arg). When expressed in heterologous cells, both Gln106Arg and Ser217Arg mutations altered hormone binding, whereas the Arg262Gln mutation altered activation of phospholipase C. The propositus, a 30-yr-old man, displayed complete idiopathic hypogonadotropic hypogonadism with extremely low plasma levels of gonadotropins, absence of pulsatility of endogenous LH and alpha-subunit, absence of response to GnRH and GnRH agonist (triptorelin), and absence of effect of pulsatile administration of GnRH. The two sisters, 24 and 18 yr old, of the propositus displayed, on the contrary, only partial idiopathic hypogonadotropic hypogonadism. They both had primary amenorrhea, and the younger sister displayed retarded bone maturation and uterus development, but both sisters had normal breast development. Gonadotropin concentrations were normal or low, but in both cases were restored to normal levels by a single injection of GnRH. In the two sisters, there were no spontaneous pulses of LH, but pulsatile administration of GnRH provoked a pulsatile secretion of LH in the younger sister. The same mutations of the GnRH receptor gene may thus determine different degrees of alteration of gonadotropin function in affected kindred of the same family.

Adult↗
PubMed1999

Antimüllerian hormone in patients with hypogonadotropic hypogonadism.

Antimullerian hormone (AMH) is produced by immature Sertoli cells until pubertal maturation. At puberty, elevation of serum testosterone correlates with a decrease in serum AMH. To further investigate the hormonal control of AMH secretion, serum AMH levels were measured in 20 normal men (20-60 yr), in 12 patients (19-30 yr) with congenital hypogonadotropic hypogonadism (CHH), and in 18 patients (19-65 yr) with acquired hypogonadotropic hypogonadism (AHH) either untreated or during testosterone or human chorionic gonadotropin (hCG) therapy. Mean serum AMH levels in normal adult men were low (20+/-4.9 pmol/L). In untreated CHH patients, mean serum AMH levels were significantly higher than in normal men (292+/-86 pmol/L, P < 0.001) and were similar to those previously reported in prepubertal boys. In men with AHH, mean serum AMH levels were also significantly increased (107+/-50 pmol/L; P < 0.01) when compared with healthy men but were less than in men with CHH. In addition, in 10 patients treated for prostate cancer, a modest but significant increase of serum AMH (from 11.4 +/-5.7 pmol/L to 49+/-9.9 pmol/L; P < 0.01) was observed 12 months after suppression of the gonadal axis with the GnRH agonist Triptorelin (3.75 mg IM once a month). Plasma testosterone (T) and serum AMH levels were measured at baseline and at 3 and 6 months in 10 HH patients (6 CHH and 4 AHH) treated with hCG (1500 IU/twice weekly for 6 months) and in 8 HH (4 CHH and 4 AHH) patients treated with T (T enanthate 250 mg/3 weeks for 6 months). hCG treatment induced an increase of plasma T (from 1.0+/-0.7 to 11+/-2.4 and 19+/-4.8 nmol/L, at 3 and 6 months respectively) associated with a dramatic decrease of serum AMH (from 314+/-93 to 56+/-30 and 17+/-4.3 pmol/L). The similar increase in plasma T levels (from 1.4+/-1.0 to 15.6+/-4.2 and 23+/-6.2 ng/mL) obtained with exogenous T induced a lesser decrease of serum AMH (from 221+/-107 pmol/L to 114+/-50 and 66+/-17 pmol/L, at 3 and 6 months respectively). In conclusion, high plasma AMH levels in CHH patients are related to the absence of pubertal maturation of Sertoli cells. The high AMH levels in AHH and its increase after Triptorelin-induced gonadotropin deficiency suggest that the suppression of AMH is a reversible phenomenon. Finally, the inhibition of AMH production by Sertoli cells is induced by intratesticular T.

Adult↗
PubMed1999

Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma.

Neuroendocrine tumors (NET) of the thyroid gland are rare. Apart from medullary thyroid carcinoma (MTC), metastases of gastroenteropancreatic (GEP) NET may also occur. Features of six patients (five men, one female: age range, 39-67 years) with thyroid metastases from a GEP-NET are described. Thyroid metastases were bilateral in all patients and were associated with enlarged neck lymph nodes in five. In four cases, the thyroid tumor was either the first sign of the disease (n = 2) or was an isolated site of recurrence (n = 2). The tumors were well (n = 3) or poorly differentiated (n = 3). Five tumors for which the primary site could be determined corresponded to foregut-derived tumors (3 lungs, 1 thymus and 1 pancreatic NET). One tumor demonstrated calcitonin (CT) production as shown by immunohistochemistry and elevated plasma CT levels. However, the disease history and the clinical features strongly favored a metastasizing GEP-NET. No tumoral RET proto-oncogene mutation was found in this patient. The differential diagnosis between metastatic GEP-NET and MTC is crucial because prognosis, work-up, and treatment differ greatly.

Adult↗
PubMed1999

Catecholamine production in patients with gastroenteropancreatic neuroendocrine tumors.

OBJECTIVE: Amine precursor uptake and decarboxylation is a classical feature of gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Production of catecholamines was studied in GEP NET and non-NET patients. DESIGN: A cross-sectional study was undertaken. METHODS: We studied catecholamine and metabolite secretion in 115 consecutive GEP NET patients and in 20 patients with non-NET. After specific extraction, vanilmandelic acid, homovanilic acid, catecholamines (norepinephrine, epinephrine, dopamine) and methoxylated derivates (metanephrine, normetanephrine, methoxytyramine) in urinary extracts were analyzed by high performance liquid chromatography. Results were indexed to the 24-h urinary creatinine levels. RESULTS: Among the 115 patients with NET, 9 (8%) had an increase of at least one urinary catecholamine or metabolite; in 7 out of the 9 the increase was slight being less than twice the upper value of the normal range. Elevated urinary dopamine (3 patients), methoxytyramine (6 patients), norepinephrine (2 patients) and normetanephrine (2 patients) were found. No increased urinary excretion of epinephrine nor metanephrine was observed. An adrenal mass existed in one of these nine patients but metaiodobenzylguanidine scintigraphy was negative as was immunohistochemistry for epithelial markers. None of the 20 patients with non-NET demonstrated an increased excretion of catecholamine or metabolites. No relationships were found between catecholamine and metabolite excretions and patients' tumor and treatment characteristics. CONCLUSION: Production of catecholamines and metabolites is a rare event in GEP NET patients. Histological results, including positive immunohistochemistry for epithelial markers may help to diagnose GEP NET.

Adult↗
PubMed1999

[Estrogen biosynthesis and receptors].

Most of the enzymes involved in steroidogenesis belong to the family of cytochrome P 450. Most of the corresponding genes have been cloned. The key enzyme for estradiol biosynthesis is P 450 arom. Several germline mutations have been described. These observations have lead to reconsider the role of estradiol. Estradiol plays a key role in bone growth and mineralisation and in gonadotrope regulation in male. Moreover, the recent discovery that an additional estrogen receptor (ER beta) is present in various tissues has advanced our understanding of the mechanisms underlying estrogen signalling. It suggests the existence of two previously unrecognized pathways of estrogen signalling: via the ER beta subtype in tissues exclusively expressing this subtype and via the formation of heterodimers in tissues expressing both ER subtypes. Various models have been suggested as explanations for the stricking cell and promoter-specific effects of estrogens and antiestrogens, all on the basis of the assumption that only a single ER exists. These models have to be reconsidered. Moreover, new antiestrogens with improved therapeutic profiles could be designed.

Animals↗
PubMed1999

Loss of function mutations of the GnRH receptor: a new cause of hypogonadotropic hypogonadism.

The association of hypogonadotropic hypogonadism with anosmia defines Kallmann's syndrome. The gene of the X-linked form of this syndrome has been cloned and several mutations described. However, the relatively small number of hypogonadotropic hypogonadic patients with Kallmann's gene defects supports the hypothesis that other genes may be involved. Idiopathic hypogonadotropic hypogonadism (IHH) is not associated with anosmia. The GnRH gene was excluded as a candidate gene in IHH since no abnormality was found in several patients. The action of the GnRH is mediated through a G-protein coupled receptor present in the cell membrane of gonadotropes. The GnRH receptor was thus another candidate gene. Recently, we described the first patient with partial hypogonadotropic hypogonadism without anosmia caused by loss of function mutations of the GnRH receptor. We compare this first family with a new family presenting complete hypogonadotropic hypogonadism and a variable degree of gonadotrope deficiency in the affected kindred, and discuss genotype-phenotype correlation.

Family Health↗
PubMed1998

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia.

UNLABELLED: The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7+/-0.3 (SE) years, and routinely evaluated 5.4+/-0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (< 10 microg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (-1+/-0.3, n=6), but not in GH-deficient patients given GH (-0.6+/-0.3, n=8) or in those with normal GH peak (-0.4+/-0.3, n=7). CONCLUSION: In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation.

Adolescent↗
PubMed1998

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.

UNLABELLED: During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. CONCLUSION: In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.

Bone Marrow Transplantation↗
PubMed1998

Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. Fralle group. French Acute Lymphoblastic Leukaemia study group.

We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54.8% (SD 1.9), 43.1%) (SD 2.7) and 55.6% (SD 2.2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 x 10(9)/l), circulating blastosis. haemoglobin >12 g/dl, platelet count <100 x 10(9)/l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10+ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1.1% for gender, 2.0% for age, 3.5% for leucocytosis, and 1.6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.

Age Factors↗
PubMed1998

Absence of activating mutations in the GnRH receptor gene in human pituitary gonadotroph adenomas.

The monoclonal origin of gonadotropin-secreting pituitary adenomas has been well demonstrated but only few molecular abnormalities have so far been recognized in these tumors. For many years, several authors have suggested a role for GnRH and/or GnRH receptors (GnRH-R) in the development of these pituitary adenomas. To test the hypothesis that mutant genes encoding a constitutively activated GnRH-R might be involved in the pathogenesis of these tumors, the sequence of the GnRH-R gene was analyzed in tumoral pituitary tissue obtained from ten patients (six female, four male). The pituitary gonadotropin-secreting adenoma was associated with in vivo hypersecretion of FSH, LH and/or free alpha-subunit (n = 7) or was clinically silent (normal plasma levels of gonadotropins or free alpha-subunit, n = 3). In all cases, immunocytochemical studies of the removed adenoma confirmed their gonadotroph nature by revealing positivity for FSH, LH and/or alpha-subunit. Genomic DNA was extracted from the pathological tissue obtained at neurosurgery. Eight sequencing primers were used to amplify the three exons of the GnRH-R gene from tumoral DNA. The entire coding sequence of the GnRH-R gene was sequenced in the ten adenomas. No mutation was found in any of the tumor specimens examined. In conclusion, mutations in the GnRH receptor coding sequence occur infrequently if at all in gonadotropin-secreting pituitary adenomas.

Adenoma↗
PubMed1997

Hashimoto's thyroiditis associated with Riedel's thyroiditis and retroperitoneal fibrosis.

This article describe the case of a 38-year-old woman with simultaneous involvement of the thyroid by Hashimoto's thyroiditis and Riedels's disease, associated with retroperitoneal fibrosis and lipidic endarteritis. According to a large review of the literature on the occurrence of this rare condition the difficulty in sharply defining the two thyroid processes is discussed. The chronology of the events is analyzed, and etiopathogenic hypotheses are listed with emphasis on the relationship between the vascular lesions and the onset of the fibrosing process.

Adult↗