CONTEXT Hashimoto's thyroiditis (HT) and Graves' disease (GD), two autoimmune thyroid diseases (AITD), occur more frequently in women than in men and show an increased incidence in the years following parturition. Persisting fetal cells could play a role in the development of these diseases. OBJECTIVE Aim of this study was to detect and characterize fetal cells in blood of postpartum women with and without an AITD. PARTICIPANTS Eleven patients with an AITD and ten healthy volunteers, all given birth to a son maximum 5 years before analysis, and three women who never had been pregnant, were included. None of them had any other disease of the thyroid which could interfere with the results obtained. METHODS Fluorescence in situ hybridization (FISH) and repeated FISH were used to count the number of male fetal cells. Furthermore, the fetal cells were further characterized. RESULTS In patients with HT, 7 to 11 fetal cells per 1.000.000 maternal cells were detected, compared to 14 to 29 fetal cells in patients with GD (p = 0,0061). In patients with HT, mainly fetal CD8(+) T cells were found, while in patients with GD, fetal B and CD4(+) T cells were detected. In healthy volunteers with son, 0 to 5 fetal cells were observed, which was significantly less than the number observed in patients (p<0,05). In women who never had been pregnant, no male cells were detected. CONCLUSION This study shows a clear association between fetal microchimeric cells and autoimmune thyroid diseases.

Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

OBJECTIVE To investigate the impact of ovarian hyperstimulation syndrome (OHSS) on thyroid function in women without thyroid disorders and to compare it with that in women with uncomplicated controlled ovarian hyperstimulation (COH). DESIGN Retrospective analysis. SETTING Tertiary referral fertility center. PATIENT(S) A total of 77 women undergoing COH of whom 25 developed OHSS and 52 had no OHSS. Women with the presence of thyroid disorders were excluded, and only women pregnant after assisted reproductive technology were included. INTERVENTION(S) Serum TSH and free T4 (fT4) levels were measured before and 2, 4, and 6 weeks after embryo transfer (ET), and thyroid peroxidase and thyroglobulin antibody levels were measured before ET to exclude thyroid autoimmunity. The diagnosis of OHSS was based on clinical, ultrasonographic, and biologic features. MAIN OUTCOME MEASURE(S) Thyroid function, OHSS. RESULT(S) Serum TSH and fT4 levels increased 2 weeks after ET in both study groups compared with prestimulation levels. In the OHSS group: TSH, 1.9 ± 0.8 mIU/L vs. 3.1 ± 1.9 mIU/L; fT4, 12.3 ± 1.4 ng/L vs. 13.4 ± 2.1 ng/L. In the no-OHSS group: TSH, 2.1 ± 1.1 mIU/L vs. 2.6 ± 1.9 mIU/L; fT4, 13.0 ± 1.7 ng/L vs. 13.8 ± 1.6 ng/L. The increment was comparable between both study groups. CONCLUSION(S) Serum TSH levels increased significantly after COH in a comparable way in both study groups, when no thyroid disorders were present.

Background: Although an increased risk for death after hip fracture is well established, whether this excess mortality persists over time is unclear. Purpose: To determine the magnitude and duration of excess mortality after hip fracture in older men and women. Data Sources: Electronic search of MEDLINE and EMBASE for English and non-English articles from 1957 to May 2009 and manual search of article references. Study Selection: Prospective cohort studies were selected by 2 independent reviewers. The studies had to assess mortality in women (22 cohorts) or men (17 cohorts) aged 50 years or older with hip fracture, carry out a life-table analysis, and display the survival curves of the hip fracture group and age- and sex-matched control groups. Data Extraction: Survival curve data and items relevant to study validity and generalizability were independently extracted by 2 reviewers. Data Synthesis: Time-to-event meta-analyses showed that the relative hazard for all-cause mortality in the first 3 months after hip fracture was 5.75 (95% CI, 4.94 to 6.67) in women and 7.95 (CI, 6.13 to 10.30) in men. Relative hazards decreased substantially over time but did not return to rates seen in age- and sex-matched control groups. Through use of life-table methods, investigators estimated that white women having a hip fracture at age 80 years have excess annual mortality compared with white women of the same age without a fracture of 8%, 11%, 18%, and 22% at 1, 2, 5, and 10 years after injury, respectively. Men with a hip fracture at age 80 years have excess annual mortality of 18%, 22%, 26%, and 20% at 1, 2, 5, and 10 years after injury, respectively. Limitations: Cohort studies varied, sometimes markedly, in size, duration of observation, selection of control populations, ascertainment of death, and adjustment for comorbid conditions. Only published data that displayed findings with survival curves were examined. Publication bias was possible. Conclusion: Older adults have a 5- to 8-fold increased risk for all-cause mortality during the first 3 months after hip fracture. Excess annual mortality persists over time for both women and men, but at any given age, excess annual mortality after hip fracture is higher in men than in women. Primary Funding Source: Fund for Scientific Research and Willy Gepts Foundation, Universitair Ziekenhuis Brussel.

OBJECTIVE: To determine the prevalence of liver steatosis among asymptomatic individuals attending an out-patient clinic for a problem of overweight, and to define the discriminatory value of several characteristics for predicting liver steatosis among them. DESIGN AND PARTICIPANTS: Consecutive patients Swith a body mass index (BMI) of > or =25 kg/m2 who consented to undergo liver ultrasound and blood tests were recruited for inclusion. Receiver operating characteristic (ROC) curves were generated and statistical indices of diagnostic performance and their corresponding 95% confidence intervals (95% CI) were computed. Logistic regression analyses were performed to determine whether a combination of characteristics could improve diagnostic accuracy. RESULTS: We enrolled sixty-eight subjects (mean BMI, 37.5 kg/m2), of whom 39 (57.4%) had liver steatosis on ultrasound. Logistic regression analyses indicated that only 3 variables were significantly and independently correlated with liver steatosis: female gender, low adiponectin levels, and high insulin resistance index. A composite index for predicting liver steatosis was calculated by summing the risk factors of female gender, low adiponectin, and insulin resistance index (FAIR score). The accuracy of this score was determined by ROC analysis to be 0.85 (95% CI, 0.74-0.96; P < 0.001). The presence of two or more risk factors (FAIR score > or =2) had a sensitivity, specificity, positive predictive value, and negative predictive value of 77%, 91%, 92%, and 74%, respectively. The likelihood ratio for a positive result was 8.43. CONCLUSIONS: Among asymptomatic overweight individuals attending an out-patient clinic, the prevalence of liver steatosis on ultrasound is 57%. Female gender, the insulin resistance index, and low adiponectin are significant and independent predictors of liver steatosis. A combination of these three factors allows sensitivity and specificity for non alcoholic fatty liver of 77% and 91%, respectively.

The demography of dyslipidemia has changed towards a more complex atherogenic dyslipidemia involving increased levels of LDL cholesterol, in particular highly atherogenic small dense particles, hypertriglyceridemia and low HDL cholesterol, together with increased levels of markers of inflammation, thrombogenesis and endothelial dysfunction. Statins were shown to significantly lower cardiovascular morbidity and mortality, but treated patients are still left with a high residual risk, in particular for those with metabolic syndrome, type 2 diabetes, or low HDL cholesterol levels. Fibrates have been shown to reduce plasma triglycerides and increase HDL cholesterol, while improving inflammation, thrombogenesis and endothelial dysfunction. Clinical trials with fibrates have demonstrated their potential to reduce cardiovascular morbidity and mortality too, often through other mechanisms than those of statins. Combination trials of statins with fibrates have shown a more complete improvement of lipid profile and risk markers than each class separately. In contrast with gemfibrozil, fenofibrate does not interact significantly with the pharmacokinetics of statins, and its combination with statins has been shown to have a low risk of muscular side-effects or liver toxicity. The ACCORD outcome trial is exploring possible benefits of the combination of fenofibrate with statins on morbidity and mortality of patients with type 2 diabetes.

BACKGROUND: The efficacy and the minimally invasive nature of the fully transnasal endoscopic procedure in the treatment of pituitary adenomas and other lesions of the sellar area have been widely reported in the literature. Many authors observed similar results in terms of the correction of hormonal hypersecretion in functioning pituitary adenomas using endoscopic endonasal surgery or the traditional microscopic technique. We report the endocrinologic outcome in 2 series of patients operated on at the same institution for functioning pituitary adenomas using these 2 different techniques. METHODS: This study includes 2 successive series of 60 consecutive patients presenting with a hormonally active pituitary adenoma operated on by the same surgeon. The surgical results obtained in the most recently operated group using a fully endoscopic endonasal technique were compared with those obtained previously using the traditional microsurgical transsphenoidal procedure. The classification of tumors into 4 grades according to Hardy was based on modern MRI and intraoperative findings. RESULTS: The overall remission rate of hypersecretion was 63% in the endoscopic group compared with 50% in the microsurgical group. The most obvious difference between the 2 groups was observed in noninvasive macroadenomas. In this specific grade of tumors, the remission rate of hypersecretion obtained using endoscopy was 78% compared with 43% using microsurgery. The endocrinologic results achieved for microadenomas were similar in the 2 groups. Postoperative CSF leaks occurred more frequently (6 cases) in the endoscopic group. CONCLUSIONS: In our experience, fully endoscopic transsphenoidal surgery for functioning pituitary adenomas leads to a better endocrinologic outcome for noninvasive macroadenomas compared to the traditional microsurgical technique. However, morbidity with the endoscopic technique was higher in terms of the rate of postoperative CSF leaks.

Abstract In the rat two major molecular variants of prolactin are recorded i.e. 23,000 M(r) and glycosylated 26,000 M(r). In order to further characterize the glycosylated 26,000 rat prolactin molecular variant, rat pituitary cell lysates were digested with several glycoen-zymes and the digestion products submitted to sodium dodecyl sulphate polyacrylamide gel electrophoresis and subsequent immunoblotting. The results were as follows: treatment with 1) neuraminidase, specific for sialic acid, yielded an M(r) decrease of the glycosidic variant from 26,000 to 24,500, 23,800, 23,000 and 22,000; 2) endo-alpha-N-acetylgalactosaminidase, which releases the disaccharide Gal (beta 1-3) GalNac from O-glycans, split 26,000 rat prolactin into a doublet of M(r) 26,000 to 25,500; and 3) mixed exoglycosidases from Turbo cornutus caused a gradual M(r) shift from 26,000 to 23,000. Affinity chromatography on wheat germ agglutinin Sepharose 6MB and soybean agglutinin agarose of rat pituitary homogenates and competitive inhibition tests showed that glycosylated rat prolactin has distinct affinity for these lectins. From the experimental data it is proposed that glycosylated rat prolactin is O-linked through threonine by the disaccharide Gal (beta 1-3) GalNac and possesses at least GalNac, and/or Gal and sialyl residues.