A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.

S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.

Pregnancy is accompanied by changes in thyroid function, but limited data are available on these changes in the very first weeks of pregnancy. Yet, T(4) plays a major role in implantation and early fetal development. We sought to determine thyroid function during this period and during the first trimester, in pregnancies achieved by assisted reproductive technology. Furthermore, the thyroid hormone profile was compared between euthyroid women with (TAI+) and without (TAI-) thyroid autoimmunity. We prospectively analyzed data from 35 women who received ovarian hyperstimulation (OH) and presented clinical pregnancies. The mean age of the women was 32 +/- 5 yr. Thyroid function tests [serum TSH and free T(4) (FT(4))] and thyroid antibody status were determined before OH (baseline values) and every 20 d after ovulation induction during the first trimester of pregnancy. Serum TSH and FT(4) increased significantly at d 20, compared with baseline values (3.3 +/- 2.4 vs. 1.8 +/- 0.9 mU/liter; P < 0.0001 and 13.2 +/- 1.7 vs. 12.4 +/- 1.9 ng/liter; P = 0.005). During the first trimester of pregnancy, there was a significant change over time for TSH and FT(4) (P < 0.001 and P = 0.005, respectively). Nine women (27%) were TAI+. The TSH curve among these TAI+ women was significantly higher compared with TAI- women (P = 0.010). The opposite was observed for the FT(4) curve (P = 0.020). In conclusion, the present study showed a significant increase of serum TSH and FT(4) levels after OH in the very first period of pregnancy compared with pre-OH levels and a significant impact of TAI on the thyroid hormone profile during the first trimester. This provides evidence for an altered thyroid function in euthyroid TAI+ patients.

Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.

This analysis shows that inhibin B, either alone or in combination with serum FSH, fails to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.

Abstract 2Objective: Although left dorsolateral prefrontal cortical (DLPFC) repetitive Transcranial Magnetic Stimulation (rTMS) is used to treat major depression, its underlying neurophysiological working mechanism remains to be determined. Prior research suggested that the clinical effects could be mediated by affecting the hypothalamic-pituitary-adrenal (HPA) system, but experimental studies in healthy individuals did not yield clear results. However, in healthy individuals, the influence of HFrTMS on the HPA-system may only be detected when it is challenged.Methods: In 30 rTMS naïve healthy females we evaluated the effect of one sham-controlled high frequency (HF)-rTMS session applied to the left DLPFC on the stress hormone cortisol by collecting salivary cortisol samples. In order to increase stress levels, five minutes after stimulation, all participants performed the Critical Feedback Task (CFT), during which they were criticized on their performance. To take possible mood influences into account, all participants were also assessed with Visual Analogue Scales (VAS).Results: The experimental procedure did not affect mood differently in the real or sham stimulation.Area under the curve (AUCi) analysis showed that one real HF-rTMS session significantly influenced HPA-system sensitivity, as demonstrated by a decrease in cortisol concentrations. The sham procedure yielded no effects.Conclusions: In line with former observations in major depression, one real left DLPFC HF-rTMS session significantly influenced HPA-system sensitivity in experimentally stressed females, resulting in decreases in cortisol levels.

Background: Thyroid autoimmunity (TAI) is frequent in infertile women, but to what extent thyroglobulin autoantibodies (Tg-Abs) contribute to TAI is unclear in the literature. The aims of the present study were to determine the prevalence of TAI in women consulting for fertility problems and to investigate the impact of isolated Tg-Abs, isolated thyroid peroxidase autoantibodies (TPO-Abs), and the presence of both autoantibody types on thyroid function. Furthermore, thyroid function was compared between women with and without TAI and between infertile and fertile women. Methods: A cross-sectional data analysis nested within an ongoing prospective cohort study was performed in order to determine the prevalence of TAI in unselected women consulting our tertiary referral center for reproductive medicine (CRM). The women underwent a determination of serum thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and Tg-Abs. The cause of infertility, age, body-mass index (BMI), and smoking habits were recorded. Results: The prevalence of TAI was 16% (163/992). In 8% of cases, both types of autoantibodies were present, in 5% isolated positive Tg-Abs were found, and 4% had isolated positive TPO-Abs ( p = 0.025 and p = 0.003 respectively). The prevalence of TAI was significantly higher in infertile women as compared to that in fertile controls (19% vs. 13%; p = 0.047). The median serum TSH level was significantly higher in the women with TAI and with isolated positive Tg-Abs compared to that in women without TAI (1.83 [1.44] and 1.90 [0.85] vs. 1.47 [0.94] mIU/L; p <0.001 respectively). The median FT4, age, BMI, and smoking habits were comparable between the study groups. Conclusions: The prevalence of TAI was higher in infertile women as compared to fertile women consulting our CRM. Five percent of the women had isolated positive Tg-Abs and a significantly higher serum TSH compared to that in women without TAI.

Objective: Macroprolactinemia, which can be detected by a polyethylene glycol (PEG) precipitation test, is a clinically and biologically heterogeneous condition. In this study, we analyzed whether the clinical presentation, the hormonal findings and the in vitro lactogenic activity differed between macroprolactinemic patients with and without circulating prolactin (PRL) -IgG complexes. Design: Clinical data were reviewed and additional hormonal studies were performed in 50 hyperprolactinemic patients with macroprolactinemia. Methods: Macroprolactinemia was identified by a PRL recovery after PEG precipitation of ,50%, as measured by an automated commercial immunoassay system and circulating PRL -IgG complexes by an abnormal PRL binding to anti-IgG agarose. Results: PRL -IgG complexes were found in 46 patients. The origin of hyperprolactinemia in these 46 patients was idiopathic in 33 patients, while a pituitary lesion or stalk magnetic resonance imaging or computed tomography scan was detected in 13 patients found compression. Galactorrhea was found in 11 of these 46 patients, while this condition was present in three of the four patients without circulating PRL -IgG complexes. The median free PRL concentration was significantly lower in patients with PRL -IgG complexes than in the group without complexes (243 vs 969 mIU/l; P , 0.005), whereas median total PRL immunoreactivity and median PRL bioactivity in the Nb2 assay were not significantly different. In patients with circulating PRL -IgG complexes, Nb2 bioassay results correlated significantly with total PRL immunoreactivity (r ¼ 0.64; P , 0.0001), but not with free PRL results (r ¼ 0.24; P , 0.17). Conclusions: These results indicate that PRL -IgG complexes (i) account for most cases of macroprolactinemia -as identified by PEG precipitation -in hyperprolactinemic patients presenting with a variety of diagnoses, (ii) are not associated with a specific clinical presentation, (iii) can be found in patients with diverse pituitary pathologies, and (iv) possess an in vitro lactogenic activity in the Nb2 bioassay in relation to their immunoreactivity.