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Low vitamin D serum level has been reported in women with polycystic ovary syndrome (PCOS) compared to controls. A few in vitro studies showed that the bioactive form of vitamin D is able to modulate the expression of the anti-Müllerian hormone (AMH) gene. However, in vivo studies failed to demonstrate clearly whether low vitamin D3 serum level is involved in the AMH excess of PCOS. This prospective study evaluates serum vitamin D3 and AMH levels in women with PCOS and in controls, before and after vitamin D supplementation.Among vitamin D deficient patients, 23 patients with PCOS were compared to 27 women with normal ovarian reserve (NOR). The vitamin D deficient patients received a vitamin D supplementation according to the depth of their insufficiency. For the 23 patients with PCOS and the 27 controls, serum AMH assay and serum calciotropic hormone assays [25-hydroxyvitamin D (25[OH]D), 1,25 dihydroxyvitamin D (1,25[OH]Serum 25(OH)D levels before treatment were statistically lower in PCOS women than in NOR patients (P0.05), even after adjustment for BMI, age and AMH level, but not after adjustment for waist circumference measurement. No difference in the serum AMH levels before and after treatment was observed neither in PCOS patients nor in NOR patients. In both groups, 25(OH)D serum levels were not related to serum AMH levels, serum 1,25(OH)We found no evidence that serum calciotropic hormones are linked to circulating AMH levels, particularly in PCOS.

Resume Le besoin d’une imagerie calibree des ovaires polykystiques (OPK) est plus fort que jamais depuis la conference de consensus qui s’est tenue a Rotterdam du 1er au 3 mai 2003. Cependant, imager les ovaires polykystiques n’est pas une procedure facile et requiert un certain savoir-faire technique et medical. L’echographie en deux dimensions reste l’examen standard d’imagerie des OPK et la definition des OPK dans le consensus actuel retenue a la conference de consensus ASRM/ESHRE repose sur cette technique : 12 ou davantage de follicules mesurant 2 a 9 mm de diametre et/ou un volume ovarien augmente au-dela de 10 cm3. Cependant, ces seuils necessitent d’etre revus avec les nouveaux appareils possedant une meilleure resolution spatiale et avec l’apparition de l’echographie 3-D. Les etudes en doppler et en imagerie par resonance magnetique (IRM) sont rarement utiles au diagnostic mais peuvent etre interessantes en recherche clinique.

Resume 1. La classification dite de Rotterdam doit etre utilisee pour la definition du SOPMK: existence d’une anomalie du cycle menstruel : amenorrhee, oligospaniomenorrhee ou cycles longs ; existence d’une hyperandrogenie clinique et/ou biologique ; presence d’ovaires polykystiques (OPK) a l’echographie. Deux criteres sur trois suffisent, apres exclusion des autres diagnostics. 2. La classification de Ferriman et Gallway ne doit pas etre utilisee pour faire le diagnostic d’hirsutisme. 3. La definition echographique de l’OPK repond a des criteres precis qui doivent figurer dans le compte-rendu : presence d’au moins 12 follicules mesurant 2–9 mm de diametre dans chaque ovaire ; et/ou volume ovarien augmente > a 10 ml. 4. L’elevation de la LH plasmatique ne doit plus etre recherchee. Le test a la GnRH est inutile. 5. La recherche d’anomalies metaboliques doit etre systematique et repose sur les criteres suivants: poids, taille, calcul de l’IMC, tour de taille, pression arterielle ; biologie: glycemie, triglycerides, cholesterol HDL. 6. En cas d’obesite (IMC > 30 kg/m2), l’hyperglycemie par voie orale (HPGO) est recommandee si la glycemie a jeun est normale. 7. Le Citrate de Clomiphene (CC) demeure le traitement de premiere intention pour l’induction de l’ovulation. Si l’IMC est > 30, il doit etre precede d’une amelioration de l’etat metabolique par des mesures hygieno-dietetiques.

Although treatment and survival are the primary focus of health-care patients, with cancer survivors living longer it is now appropriate to consider their quality of life after treatment, including the possibility of becoming parents. There are several options for fertility preservation in cancer patients. Even though most of them are still experimental and their efficacy and reliability have not been determined, especially in women. The most successful alternative for female survivors is embryo cryopreservation, an approach not suitable for many single or virgin women or even possible for prepubertal girls. Reports of live birth after transplantation of human ovarian tissue have reinforced the clinical potential of ovarian tissue banking for fertility preservation. Many exciting studies are underway to improve the efficacy and solve the problems with current fertility preservation strategies, especially for in vitro culture of cryopreserved tissue or follicles. Continuous efforts to improve current strategies and to develop new strategies will benefit many women and children who are facing premature ovarian failure and sterility.

Ectopic prolactin secretion remains exceptional and originates mainly from malignant tumors. We report the case of a 47-year-old woman who presented amenorrhea leading to unravel important hyperprolactinaemia (269 ng/mL) with no hypothalamo-pituitary mass on magnetic resonance imaging (MRI). Pelvic imaging revealed the presence of a large pelvic mass that originated from the mesocolon. After complete surgical extraction, histological examination was in favour of a "perivascular epithelioid cell tumor" (PEComa). Prolactin levels normalized after surgical extraction and remained normal after a 3-year follow-up, totally free of tumour recurrence and/or metastasis. This suggests that hyperprolactinaemia was most likely related to the PEComa, despite negative reactions with antiprolactin antibodies at immunohistochemistry. Alternatively to a direct prolactin secretion by the tumor, one could hypothesize that the tumour secreted a prolactin stimulating factor or a dopamine antagonist that could not be identified. In conclusion, in face of an important hyperprolactinaemia without any hypothalamic-pituitary mass, it remains important to search for an ectopic prolactin production, such as a PEComa.

We describe the clinical presentation, biochemical features, diagnostic criteria, clinical course and differential diagnosis in three cases of feminizing adreno-cortical carcinoma (FACC) with a review of the literature. Patients From 1970 throughout December 2003 among a series of 801 adrenalectomies, three had been performed for FACC. Results Age at presentation was 74, 63 and 23 years. Estradiol hypersecretion was observed in 3/3 patients, 17 OH progesterone was elevated in 2/3 patients and both of them had a diminution of testosterone, delta 4 androstenedione was elevated in 1/3 patients. Imaging studies suggested malignancy in 3/3 patients by the presence of necrosis, heterogeneity, calcifications, size of the tumor and compression of adjacent organs. All patients were stage III at presentation and had a Weiss score 6. Size and weight of the tumors were 30, 20, 15cm and 3750, 480 and 275g respectively. All 3 patients received mitotane and cortisone post-operatively and at follow up (7, 3 and 2 years) all 3 died of the disease. Conclusions Feminizing adreno-cortical carcinomas in adults are exceedingly rare (1-2% of adreno-cortical carcinomas). Tumors are huge and even after surgery for cure their prognosis is worse than for other varieties of adreno-cortical carcinomas either secreting or non secreting. Early diagnosis and treatment may improve overall prognosis.

Cet article rapporte le cas d’un homme presentant une ataxie cerebelleuse d’evolution progressive depuis l’enfance associee a un hypogonadisme hypogonadotrope partiel decouvert au decours d’un bilan d’infecondite. L’association de ces deux entites cliniques a ete decrite dans plusieurs syndromes rares : l’ataxie de Holmes, le syndrome de Boucher-Neuhauser et le syndrome de Richards-Rundle. Ces trois associations syndromiques sont definies uniquement sur des criteres cliniques et n’ont pas encore ete genetiquement determinees ; cela ne permet donc pas actuellement d’etablir de diagnostic de certitude. Le cas que nous rapportons abonde dans le sens d’une entite syndromique associant une ataxie spino-cerebelleuse autosomale recessive avec un hypogonadisme hypogonadotrope qui regroupe plusieurs entites genotypiques.

Introduction L’insuffisance ovarienne prematuree (IOP) se definit par une amenorrhee et un taux de FSH superieur a 25 UI/L. Dans environ 70 % des cas, aucune etiologie n’est retrouvee. Ces dernieres annees, de nombreux genes candidats ont ete identifies. Cependant, leur imputabilite et leur prevalence restent mal connues. Objectif Evaluer la prevalence de mutations de genes candidats dans une cohorte multicentrique de patientes avec IOP. Materiel et methodes Une analyse par sequencage a haut debit utilisant une puce contenant 18 genes candidats a ete realisee chez 288 patientes. Les anomalies retrouvees ont ete classees en « mutation » ou « variant rare » a l’aide de logiciels de prediction (SIFT, Polyphen-2, mutation taster). Resultats La repartition des patientes etait de 12,5 % de patientes avec une amenorrhee primaire, 87,5 % avec une amenorrhee secondaire. Au moins, une mutation a ete identifiee chez 22 % des patientes et 2 mutations chez 1,4 %. NOBOX etait le gene le plus frequemment mute (9 % des cas). Des variants rares presumes non pathogenes etaient presents chez 33 % des patientes. Parmi les 47 cas ayant une forme familiale, 17 % avaient une mutation (versus 23 % dans les formes non familiales). En cas d’amenorrhee primaire, 28 % des patientes presentaient une mutation. Discussion Cette etude sur une large cohorte a identifie des anomalies genetiques a priori non pathogenes et des mutations chez respectivement 33 et 22 % des patientes. Ces resultats illustrent la precaution necessaire dans l’interpretation des resultats, notamment pour le conseil genetique des patientes avec IOP.

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease affecting 10 to 15% of women. Menstrual disorders, hyperandrogenism and ultrasonographic aspect of ovaries are typical of the disease and are established diagnostic criteria. But PCOS has also long term complications frequently forgotten and underestimated. During pregnancy, gestational diabetes and gestational hypertensive disorders can occur. At an older age, metabolic disease such as glucose intolerance, type 2 diabetes or dyslipidaemia are frequently described. Women with PCOS have increased classical cardiovascular risks and increased subclinical cardio-vascular disease without proven increase of cardiovascular morbidity and mortality. Finally, endometrial cancer seems to be more frequent in women with PCOS. Therefore, PCOS have numerous long-term health risks and a life-long follow-up is necessary for these women "at-risk" to detect and prevent complications as soon as possible.

1. The Rotterdam classification should be used to define PCOS in the event of: menstrual cycle anomalies; amenorrhoea, oligomenorrhoea or long cycles, clinical and/or biochemical hyperandrogenism and ultrasound appearance of polycystic ovaries. 2. The presence of two of these three criteria is sufficient once all other diagnoses have been ruled out. 3. Diagnosis of hirsutism should not be based on the Ferriman-Gallway score. 4. The ultrasound definition of PCOS contains precise criteria that must be included in the report: presence of at least 12 follicles in each ovary measuring 2-9 mm in diameter, and/or increase in ovary size>10 ml. 5. Screening for elevated plasma LH no longer necessary. Testing for GnRH serves no purpose. 6. Routine screening for metabolic abnormalities should be carried out systematically based on weight, height and BMI, waist circumference, blood pressure and laboratory parameters: plasma glucose, triglycerides, HDL cholesterol. 7. In the case of obesity (BMI>30 kg/m(2)), oral glucose tolerance testing (OGTT) is recommended where fasting serum glucose is normal. 8. Clomiphene citrate (CC) remains the first-line therapy for ovulation induction. In patients with BMI>30, it should be preceded by improvement of metabolic status through appropriate lifestyle modifications.

Although treatment and survival are the primary focus of health-care patients, with cancer survivors living longer it is now appropriate to consider their quality of life after treatment, including the possibility of becoming parents. There are several options for fertility preservation in cancer patients. Even though most of them are still experimental and their efficacy and reliability have not been determined, especially in women. The most successful alternative for female survivors is embryo cryopreservation, an approach not suitable for many single or virgin women or even possible for prepubertal girls. Reports of live birth after transplantation of human ovarian tissue have reinforced the clinical potential of ovarian tissue banking for fertility preservation. Many exciting studies are underway to improve the efficacy and solve the problems with current fertility preservation strategies, especially for in vitro culture of cryopreserved tissue or follicles. Continuous efforts to improve current strategies and to develop new strategies will benefit many women and children who are facing premature ovarian failure and sterility.

Chez la femme, l’hormone anti-mullerienne (AMH) s’exprime au niveau des cellules de la granulosa, tout au long de la croissance folliculaire. Le dosage de l’AMH est tres correle au compte folliculaire antral calcule a l’echographie, et est donc un bon marqueur de la reserve ovarienne. Ses indications sont essentiellement lors de l’evaluation d’un trouble du cycle, pour depister un syndrome des ovaires polymicrokystiques ou une baisse de la reserve ovarienne. Dans le cadre de l’AMP, ce dosage aide a choisir le protocole de stimulation ovarienne et la dose de gonadotrophines, afin d’optimiser la reponse a la stimulation et de limiter les risques d’hyperstimulation ovarienne et d’annulation de cycle pour hyporeponse. Enfin, ce dosage permet d’evaluer la reserve ovarienne apres traitements ovario-toxiques, d’evaluer l’impact de ces traitements et d’envisager une preservation ovocytaire si possible. Les techniques de dosage de l’AMH sont en evolution, ce qui permettra une homogeneisation des resultats, avec des seuils d’AMH generalisables. L’inhibine B ne s’exprime que dans les follicules selectionnables. Mis a part le diagnostic et le suivi des tumeurs de la ganulosa, ce dosage n’est plus utilise chez la femme. Chez l’homme adulte, en revanche, le dosage de l’inhibine B est un complement utile pour l’evaluation d’un trouble de la spermatogenese, en complement du dosage de la FSH. Chez le garcon, le dosage de l’AMH est utile dans les situations de pubertes precoces, retardees, les hypogonadismes hypogonadotropes et les insuffisances testiculaires. Enfin, ce dosage aide au diagnostic et a la definition des anomalies du developpement sexuel.

We describe the clinical presentation, biochemical features, diagnostic criteria, clinical course and differential diagnosis in three cases of feminizing adreno-cortical carcinoma (FACC) with a review of the literature.From 1970 throughout December 2003 among a series of 801 adrenalectomies, three had been performed for FACC.Age at presentation was 74, 63 and 23 years. Estradiol hypersecretion was observed in 3/3 patients, 17 OH progesterone was elevated in 2/3 patients and both of them had a diminution of testosterone, delta 4 androstenedione was elevated in 1/3 patients. Imaging studies suggested malignancy in 3/3 patients by the presence of necrosis, heterogeneity, calcifications, size of the tumor and compression of adjacent organs. All patients were stage III at presentation and had a Weiss scoreor=6. Size and weight of the tumors were 30, 20, 15cm and 3750, 480 and 275g respectively. All 3 patients received mitotane and cortisone post-operatively and at follow up (7, 3 and 2 years) all 3 died of the disease.Feminizing adreno-cortical carcinomas in adults are exceedingly rare (1-2% of adreno-cortical carcinomas). Tumors are huge and even after surgery for cure their prognosis is worse than for other varieties of adreno-cortical carcinomas either secreting or non secreting. Early diagnosis and treatment may improve overall prognosis.

The Polycystic Ovary Syndrome (PCOS) includes three phenotypic compartments, not always fully associated, consisting in hyperandrogenism, anovulation and metabolic syndrome, secondary to insulin resistance. The pathophysiological grounds lie upon two main components, i.e.: the theca-interstitial cell (TIC) and the granulosa cell (GC) dysregulations, the former accounting for hyperandrogenism and the latter for anovulation, and both of them being under the influence of hyperinsulinism. The former mainly results from an enzymatic overactivity, yielding an exaggerated output of androgens by the TIC, but the type(s) of enzymes as well as the genetic or adaptative nature of its (their) dysregulation are still controversial. The main consequence of the CG dysregulation is the follicular arrest just before the time of dominance. This might result from an intrinsic abnormality in CG, involving the IGFs and/or the Inhibin/Activin/Follistatin systems. Alternatively, the CTI might have deleterious effects on GC, mainly via the intra-ovarian hyperandrogenism. The latter should not be regarded any more as an atretogenic phenomenon. It is closely related to the two main morphological features of PCOS, i.e.: the stromal hyperplasia and the excessive follicular number.

Some technical improvements have allowed to minimize the frequency of severe complications following fractionated pituitary conventional radiotherapy, without altering its efficiency. "Conformational" radiotherapy is currently under development, aiming at the best fitting of the tumor borders to the irradiation zone, by the means of stereotactic imaging. More recently, radiosurgery has been proposed for pituitary adenomas. It consists in a single high radiation dose to the tumor, by the means of either cobalt minibeams (Gamma Unit) or photon beams from a linear particle accelerator. These techniques require the use of a stereotactic frame and precise 3D imaging in order to tightly superimpose the target volume to the reference isodose. They must not be viewed as an alternative to conventional radiotherapy. They can be applied only to small lesions (less than 20 mm in their maximal axis) which are distant (5 mm) from the optic chiasma and nerves. Their efficiency is similar to the one of fractionated conventional radiotherapy, with a shorter response time. In conclusion, radiotherapy can be used safely for pituitary adenomas. It remains however a second line treatment, when surgery has been incomplete and when a simple, effective and inexpensive medical treatment is not possible.

Inhibins and activins are structurally-related dimeric proteins mainly produced by the gonads (Sertoli cells and granulosa cells) under the stimulation of pituitary FSH. Inhibins are 32-kD glycoproteins consisting of an alpha subunit and one of two beta subunits (beta A or beta B) leading to inhibin A or B, respectively. Activins are made of two beta subunits either identical (activin A or B) or not (activin AB). These regulatory peptides are involved in an endocrine feedback loop: inhibins decrease and activins stimulate the biosynthesis and release of pituitary FSH selectively. Beside their endocrine action that has led to the discovery of these peptides, we report main experimental data showing that activins and inhibins may act as paracrine and autocrine factors within the gonads on an antagonistic mode. Inhibins and activins seem to be involved in the regulation of spermatogenesis in males and in follicular maturation in females. Potential involvements of inhibins and activins in the pathophysiology of reproduction are discussed.

Plasma renin activity (P.R.A.) and plasma aldosterone were measured in twelve patients having hypopituitarism. Both mean values of this group were significantly lower than in normal subjects (P.R.A. recumbent: p less than 0.001, upright: p less than 0.001, plasma aldosterone: recumbent: p less than 0.02, upright: p less than 0.005). Hyporeninism is a controversed feature in hypopituitarism. Our preliminary data suggest that it is not directly correlated to ACTH or cortisol deficiency. Nevertheless it may explain the hypoaldosteronism prior reported in such patients.