Serum under-carboxylated osteocalcin levels in women with polycystic ovary syndrome: weight-dependent relationships with endocrine and metabolic traits.

BACKGROUND: Under-carboxylated osteocalcin (ucOC), the precursor substrate of bone biomarker OC is a potent regulator of energy metabolism by promoting insulin production and adiponectin synthesis and decreasing fat stores. The aim of the present study was to point out the potential role of ucOC in the physiopathology of polycystic ovary syndrome (PCOS), a common disorder defined by the constellation of anovulation, insulinresistance, hyperinsulinemia, obesity and androgen excess. METHODS: In this prospective case-control investigation, 78 young premenopausal women, i.e. 52 PCOS patients and 26 age- and body mass index (BMI)-matched healthy controls, were successively enrolled. Recruitment of PCOS patients was performed according to Androgen Excess-Polycystic Ovary Syndrome (AE-PCOS) Society 2006 criteria. All study participants were subjected to clinical examination, whole-body composition assessment and measurements of serum ucOC, OC (1-49), glucose and lipids, insulin, total testosterone (TT), estradiol, sex-hormone binding globulin (SHBG), high-sensitivity C-reactive protein (Hs-CRP) and ß-CrossLaps. RESULTS: BMI-stratified multivariate analysis revealed significantly higher ucOC levels in PCOS vs. controls in lean (p = 0.001) but not overweight and obese study participants (p = 0.456). Notably, a positive correlation between ucOC and TT (p = 0.018), calculated free testosterone (cFT, p = 0.028) and serum insulin (p = 0.036), respectively, was found to be confined to the lean analysis subgroup. Furthermore, in stepwise multiple regression models, ß-CrossLaps and cFT were able to predict 46.71% of serum ucOC variability. (1-43/49)OC failed to be significantly associated to any PCOS trait. CONCLUSIONS: Circulating ucOC concentration is related to key endocrine PCOS characteristics in a weight-dependent manner. Within the bone-pancreas loop, high ucOC may favor insulin release in lean hyperandrogenic women to compensate for impaired insulin sensitivity.

Evidence for visfatin as an independent predictor of endothelial dysfunction in polycystic ovary syndrome.

OBJECTIVE: Emerging evidence links adipocyte-secreted hormones, in particular adiponectin and visfatin, to cardiovascular pathology. Although adipocytokines dysregulation is common in polycystic ovary syndrome (PCOS) within the context of obesity and insulin resistance, their participation in the process of vascular injury remains elusive. DESIGN AND METHODS: This prospective, case-control study enrolled 102 young women (69 patients with PCOS and 33 eumenorrheic age-matched controls); serum adiponectin, resistin and visfatin, testosterone, SHBG, lipids, glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (hs-CRP) were simultaneously measured in all participants. Body composition analysis was performed using dual X-ray absorptiometry. Endothelium impairment was assessed by carotid artery intimae-media thickness (CIMT) and brachial artery flow-mediated vasodilatation (FMD), respectively. RESULTS: In PCOS, both univariate and multivariate analyses evidenced that circulating visfatin was significantly related to free testosterone (P = 0·024) and brachial artery FMD (P = 0·008; P < 0·01 in multivariate analyses). By every visfatin tertile, a stepwise decrease in FMD was observed in all and PCOS only (P = 0·036), not confounded by age, body mass index, total body fat mass, testosterone, SHBG or HOMA-IR. Multiple regression analysis retained visfatin and free testosterone as independent predictors of FMD, explaining about 20% of FMD variability. Adiponectin correlated with CIMT and hs-CRP, but the association was driven by age, body mass and body fat. No relationship between resistin and endothelial markers was found. CONCLUSION: Visfatin may be a candidate to play a role in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors.

Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism.

PURPOSE: Studies that analyze the levels of osteoprotegerin (OPG) or receptor activator of nuclear factor kappa B ligand (RANKL) in hypogonadal men, the majority of whom have prostate cancer or are undergoing androgen-deprivation therapy, are few and inconclusive. METHODS: 81 men aged 69.3 ± 0.8 years (39 men with late-onset hypogonadism and 42 age-matched controls) were recruited. Serum levels of OPG, total soluble RANKL (sRANKL), total and free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone (LH), prolactin, bone-specific alkaline phosphatase (BAP) and ß-Cross Laps were assessed. RESULTS: Compared with controls, both OPG (p = 0.023) and sRANKL (p = 0.010) serum levels were increased in men with late-onset hypogonadism; however, when expressed as a ratio, sRANKL/OPG, the two groups were not significantly different. Simple and age-adjusted analyses showed that OPG was inversely related to FT and positively related to SHBG, E2 and BAP. In the patient population, LH demonstrated statistically significant correlations with both OPG (r = 0.274, p = 0.013) and sRANKL (r = 0.276, p = 0.018). Multiple regression analysis retained age, SHBG, E2 and BAP as independent predictors of OPG, explaining 27.71% of serum OPG variability. CONCLUSIONS: Late-onset hypogonadism is associated with enhanced RANKL activity. Increased bone turnover-related OPG levels may act as a coupling factor between bone resorption and formation. The results suggest anti-RANKL-agents as therapeutic tools in osteoporotic men with late-onset hypogonadism.

IFNalpha-induced recurrence of Graves' disease ten years after thyroidectomy in chronic viral hepatitis C. Case report.

In contrast to chronic or subacute thyroiditis, Graves' disease rarely complicates IFN-alpha therapy for chronic viral C hepatitis. We report the case of a 51-year-old man in whom IFN-alpha treatment was followed by recurrence of Graves' disease 10 years after thyroidectomy was performed and the patient was declared cured. Despite severe thyrotoxicosis, combined IFN-alpha and ribavirin therapy was continued and radioiodine treatment was considered for Graves' disease.