Biomedical subjects

Anne Bachelot

Publications and source records attributed to Anne Bachelot.

14 recordsLinked to original sources

PubMed2006

Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

AIMS: Conflicting results exist regarding bone mineral density (BMD), metabolism and reproductive function of adult patients with congenital adrenal hyperplasia (CAH). We evaluated the long-term outcome and the impact of chronic glucocorticoid replacement in these patients. METHODS: Physical characteristics, serum hormone concentrations, BMD and metabolism were studied in 45 consecutive CAH adult patients. RESULTS: Among the 36 women, only 14 (39%) had regular menses. Among the 27 women with classical CAH, the mean number of surgical reconstructions of virilized genitalia was 2.1 +/- 0.2. Twenty of them (74%) were sexually active. Three men presented with testicular adrenal rest tumors. Twenty-five patients (55%) had decreased BMD at the femoral neck and/or at the lumbar spine. BMI was correlated with the BMD T-score at the femoral neck (p < 0.001) and at the lumbar spine (p < 0.01). Hydrocortisone dose was negatively correlated with the BMD T-score at the femoral neck (p = 0.04). Subjects with osteopenia had a significantly lower BMI and received higher hydrocortisone dose than those with normal BMD. Overweight was found in 21 patients (47%). There was a significantly positive correlation between HOMA and BMI (p < 0.001), and between HOMA and 17-OHP levels (p = 0.016). CONCLUSIONS: Adult patients with CAH treated with long-term glucocorticoids are at risk for decreased BMD, increased BMI, and disturbed reproductive function.

Adrenal Hyperplasia, Congenital↗

PubMed2006

Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure.

BACKGROUND AND OBJECTIVE: Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF). SUBJECT AND METHODS: We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child. RESULTS: We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions. CONCLUSIONS: We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.

Adult↗

PubMed2006

Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice.

GH influences female fertility. The goal of the present study was to obtain more insight into the effect of loss of GH signalling, as observed in humans suffering from Laron syndrome, on ovarian function. Therefore, serial paraffin sections of ovaries of untreated and IGF-I-treated female GH receptor knock-out (GHR/GHBP-KO) mice were examined to determine the follicular reserve and the percentage of follicular atresia in each ovary. Our observations demonstrate that the amount of primordial follicles was significantly elevated in GHR/GHBP-KO mice, while the numbers of primary, preantral and antral follicles were lower compared with wild-type values. The reduced number of healthy growing follicles in GHR/GHBP-KO mice was accompanied by a significant increase in the percentage of atretic follicles. IGF-I treatment of GHR/GHBP-KO mice for 14 days resulted in a reduced number of primordial follicles, an increased number of healthy antral follicles, and a decreased percentage of atretic follicles. The results of the present study suggest that GH may play a role, either directly or indirectly, via for instance IGF-I, in the recruitment of primordial follicles into the growing pool. Furthermore, GH seems to protect antral follicles, directly or indirectly from undergoing atresia.

Animals↗

PubMed2005

[When and how should hyperprolactinemia be treated?].

Hyperprolactinemia affects the gonadotropic axis. Its results in women include amenorrhea, menstrual disorders and galactorrhea; in men, the frequency of macroadenomas tends to lead to problems related to sexual performance or tumor volume. Radioimmunoassays make diagnosis easy. Secondary causes of hyperprolactinemia, drug reactions in particular, must be ruled out before MRI exploration to look for a pituitary tumor. First-line treatment of prolactin adenomas is based on the use of dopaminergic agonists, especially cabergoline, because of their excellent efficacy and the risk of relapse following surgery. For patients who wish to become pregnant, the dopaminergic agonist must be continued during pregnancy for those with macroadenoma and withdrawn for women with microadenoma. When hyperprolactinemia is induced by anti-psychotic agents, treatment requires an in-depth assessment.

Dopamine Agonists↗

PubMed2005

Ovarian steroidogenesis and serum androgen levels in patients with premature ovarian failure.

Women with premature ovarian failure (POF) have been reported to have lower serum androgen levels compared with normal women. We reviewed the androgen profiles of 143 POF patients and found androgen levels above normal for postmenopausal women in 16% of these subjects. To determine the source of androgens in those women, we studied the available ovarian biopsy samples of 15 POF patients with increased androgen levels using immunohistochemistry, with a panel of antibodies directed against the main steroidogenic enzymes. Five of the ovarian biopsies exhibited abnormal follicles characterized by hypertrophied theca interna expressing steroidogenic enzymes involved in androgen synthesis. In five other biopsies, the steroidogenic activity was scarce and confined to a small number of ovarian stromal cells, sometimes situated in the proximity of follicular remnants. Finally, in five patients, we found no histological evidence of present or past follicular development beyond the quiescent follicular stage, and no steroidogenic cells were detected by immunohistochemistry. Our findings suggest that ovarian theca-derived cells are a source of androgens in some women with POF, whereas in others, as in most postmenopausal patients, the adrenals or the ovarian hilus cells may synthesize a significant quantity of androgens under LH stimulation.

Adolescent↗

PubMed2005

Corpus luteum development: lessons from genetic models in mice.

The corpus luteum is a transient endocrine gland that produces essentially progesterone, a required product for the establishment and maintenance of early pregnancy. In the absence of pregnancy, the corpus luteum will cease to produce progesterone, and the structure itself will regress in size over time. The life span and function of the corpus luteum is regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. Although the process of luteal formation and regression has been studied for several decades, many of the regulatory mechanisms involved in loss of function and involution of the structure are incompletely understood. In rodents, prolactin is the major luteotrophic hormone by maintaining the structural and functional integrity of the corpus luteum for several days after mating. Other factors involved in steroidogenesis, control of cell cycle, apoptosis, and tissue remodeling have been shown to play a role in corpus luteum development and maintenance. Especially, PGF2alpha seems to be the most potent luteolytic hormone. One of the most important advances in the study of mammalian genes has been the development of techniques to obtain defined mutations in mice. These tools enable us to target specific genes and to analyze the impact of their loss on cell fate and function. With these approaches, several receptors, transcription factors, enzymes, and other factors have been linked to corpus luteum development and maintenance. These models are helping to define mechanisms of reproductive function and to identify potential new contraceptive targets and genes involved in the pathophysiology of reproductive disorders.

Animals↗

PubMed2005

Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total body scan are not reliable criteria for cure after radioiodine treatment.

BACKGROUND: Local and regional recurrences occur in up to 20% of patients with papillary and follicular thyroid carcinoma. Diagnostic work-up and treatment modalities are still controversial, because nodal control is difficult to ascertain. We assessed the value of serum thyroglobulin (Tg) determination and of high-dose 131I total body scan (TBS) for ascertaining the absence of disease in patients who had already been treated with radioiodine and who subsequently underwent surgery. METHODS: Between 1990 and 2000, 105 patients who had been treated with radioiodine for lymph node recurrence with initial 131I uptake were included in a standardized protocol performed after withdrawal of thyroid hormone treatment: on day 1, serum Tg determination and administration of 3.7 GBq 131I; on day 4, 131I TBS; on day 5, surgery; on day 8, 131I TBS. RESULTS: In 25 patients the serum Tg obtained following thyroid hormone withdrawal was undetectable: for these patients, the 131I TBS showed uptake foci in 21 and pathology disclosed neoplastic foci in 19. In 32 patients the serum Tg ranged from 1 to 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 26 and pathology disclosed neoplastic foci in 28. In 48 patients the serum Tg level was above 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 38 and pathology disclosed neoplastic foci in 46. Thus, no uptake was found preoperatively in 20 patients, among whom pathology disclosed lymph node metastases in 16. However, both tests were negative in only two of the 93 patients in whom pathology disclosed neoplastic foci. CONCLUSION: Serum Tg levels and 131I TBS cannot be considered as reliable indicators for the absence of disease in patients already treated with 131I. However, when both tests are negative, the risk of persistent disease is minimal.

Adenocarcinoma, Follicular↗

PubMed2004

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy.

PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.

Adult↗

PubMed2004

Hyperandrogenism in a postmenopausal woman presenting with a metastatic ileum endocrine tumor.

OBJECTIVE: To elucidate the mechanism of the hyperandrogenism found in a postmenopausal woman presenting an ileum endocrine tumor with ovarian metastases. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A postmenopausal woman was referred for hirsutism. Basal plasma testosterone was high, 6.6 nM/L (normal, <or=0.7 nM/L). Pelvic magnetic resonance imaging revealed a 6-cm left ovarian mass. INTERVENTION(S): Bilateral salpingo-oophorectomy was performed. Pathological examination found a bilateral metastatic endocrine ovarian tumor, associated with a functional stroma. A primary ileum endocrine tumor was discovered and resected. MAIN OUTCOME MEASURE(S): Immunohistochemical study of the expression of steroidogenic enzymes and beta and alpha subunits of hCG. RESULT(S): Immunohistochemical expression of steroidogenic enzymes was found in the ovarian stromal tissue surrounding the tumor but not in the metastatic tumoral cells. A substantial percentage of the metastatic tumoral cells was immunopositive for the beta and alpha subunit of hCG but not the ileal cells. CONCLUSION(S): These data suggest an hCG paracrine effect of the ovarian metastases tumor on the adjacent interstitial cells, resulting in the virilization of the patient.

Cholesterol Side-Chain Cleavage Enzyme↗

PubMed2003

Effects of deletion of the prolactin receptor on ovarian gene expression.

Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.

20-alpha-Hydroxysteroid Dehydrogenase↗

PubMed2002

The role of prolactin and growth hormone in mammary gland development.

Development and differentiation of the mammary gland occur primarily during pregnancy. Females homozygous (-/-) for the null mutation of the PRL receptor (PRLR) gene are sterile due to a complete failure of blastocysts to implant. In progesterone-treated mice pregnancy is rescued but the mammary gland is severely underdeveloped. Interestingly, females hemizygous for the PRLR (+/-) in their first lactation show an almost complete failure to lactate. This phenotype disappears in the second and subsequent pregnancies in inbred 129/Sv mice but is maintained in inbred C57BL/6 mice. In GH receptor (GHR) KO mice litter size is markedly decreased, probably due to an ovarian defect. To assess the relevance of the GH and PRLRs in the mammary gland development, GHR and PRLR null epithelia were transplanted into cleared fat pads of wild-type mice. Such studies show that epithelial GHR is not required for functional mammary development. In contrast, epithelial PRLRs are required for mammary development and milk protein gene expression during pregnancy. Since ductal development is impaired in GHR -/- mice, it appears that GH signals through the stromal compartment. In summary, it is now established that GH and PRL activate Stat5 in separate compartments, reflecting their specific roles in ductal and alveolar development and differentiation.

Animals↗

PubMed2002

Inheritable forms of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid that produce calcitonin. It accounts for 5-10% of all thyroid cancers. Hereditary MTC represents 20-30% of all MTCs. It can be transmitted with an autosomal dominant pattern, either as a single entity, familial MTC, or it can arise as part of a multiple endocrine neoplasia (MEN) syndrome type 2A or 2B. The identification of hereditary MTC has been facilitated in recent years by the direct analysis of the ret proto-oncogene.

Animals↗

PubMed2002

Relationship between tumor burden and serum thyroglobulin level in patients with papillary and follicular thyroid carcinoma.

Serum thyroglobulin (Tg) is a reliable marker for detecting recurrent and persistent disease during the follow-up of patients with papillary and follicular thyroid carcinoma. The goal of this study was to assess the relationship between the serum Tg level measured after thyroid hormone withdrawal and the tumor mass in thyroid cancer patients who underwent surgery with the use of an intraoperative probe for lymph node metastases with (131)I uptake. Patients were classified into one of three groups according to the Tg level: undetectable (n = 18); 1-10 ng/mL (n = 21); and greater than 10 ng/mL (n = 33). The main clinical characteristics and the extent of the disease at the time of initial treatment were similar in these three groups. Lymph node metastases were found in 13 of the 18 patients with undetectable Tg level. Eight patients had persistent foci of uptake after surgery that were located behind the sterno-clavicular joint in six patients. The number of metastatic lymph nodes and their total surface (in mm(2)) or their total volume (in mm(3)) were significantly linked with serum Tg/thyrotropin [TSH] level (p = 0.002 and p < 0.0001, respectively). For a given metastatic surface or volume, the serum Tg/TSH value was no longer linked with the number of metastatic lymph nodes (p = 0.32), suggesting that the total surface or total volume is the characteristic that best summarizes the influence of the disease on the serum Tg/TSH level. In conclusion, patients with higher serum Tg levels tend to have more extensive disease and should undergo more aggressive treatment modalities. Nevertheless, undetectable serum Tg should not be considered as a reliable criteria to exclude a minimal tumor burden in patients who have already been treated with (131)I.

Adolescent↗

PubMed2002

Growth hormone is required for ovarian follicular growth.

To analyze the consequences of the absence of GH receptor (GHR) and GH-binding protein (GHBP) on female reproductive function, we used a mouse model in which the GHR/GHBP gene has been disrupted by homologous recombination. The major effect on reproductive function seen in GHR/GHBP knockout (KO) compared with wild-type animals is a dramatic decrease in litter size; this defect is due to a reduction of the ovulation rate. The ovulatory response to exogenous gonadotropin treatment is also 3-fold reduced in GHR/GHBP KO compared with the wild-type ovaries. These results establish that the reduced rate of ovulation is essentially due to an ovarian defect rather than a deficiency in pituitary gonadotropins. The number of follicles per ovary is markedly reduced, although all categories of follicles are represented. Interestingly, the number of healthy follicles from antral and preovulatory stages is dramatically decreased in GHR/GHBP KO in comparison with wild-type follicles. The capacity of follicles to bind LH, FSH, and IGF-I was not diminished. IGF-I treatment using micropumps is not able to rescue either fertility or ovarian responsiveness to exogenous gonadotropins, suggesting that the effect of GH is independent of IGF-I. In conclusion, these results indicate that the reduction of litter size in GHR/GHBP KO mice is the consequence of an alteration of the growth of follicles and suggest that the effects of GH effects on follicular growth are independent of IGF-I.

Animals↗