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Epicardial white adipose tissue (eWAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Adrenomedullin (AM) is a potent vasodilatator and antioxidative peptide which has been shown to play a cytoprotective role in experimental models of acute myocardial infarction. We studied, using immunohistochemistry and qRT-PCR, the expression of AM and its receptors calcitonin receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP)2 and -3 in paired biopsies of subcutaneous WAT (sWAT) and eWAT obtained from patients with coronary artery disease (CAD) or without CAD (NCAD). In eWAT obtained from NCAD or CAD patients, immunoreactivity for AM, CRLR, and RAMP2 and -3 was detected in blood vessel walls and isolated stromal cells close to adipocytes. Some of the AM positive stromal cells colocalized CD68 immunoreactivity, eWAT from CAD patients showed increased AM immunoreactivity and AM gene expression. CRLR mRNA levels were comparable in sWAT of both groups and decreased by 40-50% in eWAT, irrespectively of the coronary status. RAMP2 mRNA concentrations did not change while RAMP3 mRNA levels increased in sWAT from CAD patients. There was a positive linear relationship between eWAT 11 [beta]-hydroxysteroid dehydrogenase type 1 mRNA (11 [beta]-HSD-1, the enzyme that converts inactive to active glucocorticoids) and AM mRNA. In conclusion, we demonstrate that AM and its receptors are expressed in eWAT. Our data suggest that eWAT AM, which could originate from macrophages, is related to 11 [beta]-HSD-1 expression. AM synthesis, which is increased in eWAT during chronic CAD in humans, can play a cardioprotective role. calcitonin receptor-like receptor; receptor activity-modifying proteins; 11 [beta]-hydroxysteroid dehydrogenase type 1; coronary artery disease

Abstract Background We are hereby investigating for the first time the effect of the association ethinylestradiol30μg-drospirenone 3mg (DRP/EE30μg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS). Methods 25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30μg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention. Results The combination between DRP/EE30μg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p 6months – PCOSbasal) difference. Conclusion A 6-month course of metformin- DRP/EE30μg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445).

Obesity, only recently recognized as a health problem for the general population, demands a preventive, as well as a therapeutic approach. It is also an active risk factor for disease and disability, its complications cost enormously, and in some countries, its prevalence reached epidemic proportions. During pregnancy and breast-feeding, high levels of prolactin are recognized to influence sugar and lipid metabolism. New information about its involvement in the metabolic status outside pregnancy sustains its reevaluation as a metabolic hormone. In the white adipose tissue, prolactin inhibits lipogenesis and adipokines release, while at the pancreatic level it promotes insulin secretion. It seems that it might be implicated in promoting insulin-resistance, and thus being directly involved in the appearance of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: We are hereby investigating for the first time the effect of the association ethinylestradiol30µg -drospirenone 3mg (DRP/EE30µg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS). Methods: 25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30µg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI>25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention. Results: The combination between DRP/EE30µg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48± 1.00 vs FMD-PCOS6 months7.43± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p<0.05). Regarding hsCRP levels, there was no significant intragroup (PCOS6months--PCOSbasal) difference. Conclusion: A 6-month course of metformin- DRP/EE30µg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445). [ABSTRACT FROM AUTHOR]

The study investigated the presence of early vascular damage and chronic inflammation, and their relationships with hormonal and metabolic parameters in 45 young women with PCOS in comparison with thirty-two healthy age-matched controls. Hormonal and metabolic profiles, high sensitivity C-reactive protein (hsCRP), tumoral necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), brachial flow-mediated vasodilation (FMD) and carotid intima-media thickness (CIMT) were determined in both groups. Compared with the controls, women with PCOS had significantly lower FMD and respectively higher ET-1 levels (p=0.001). No differences were observed between the groups in terms of CIMT or inflammatory markers. In the PCOS group, ET-1 levels were significantly correlated with only testosterone concentrations (r = 0.31, p = 0.037), whereas the hsCRP levels were independently predicted only by body mass index (BMI). Within the total group, the PCOS status was the sole significant predictor of ET-1 levels and the only independent predictor of FMD. In conclusion, there is evidence of endothelial dysfunction associated with increased levels of androgen hormones in young women with PCOS. The combination of endothelial dysfunction and coexistent obesity promoting inflammation contributes to the progression of atherogenesis in PCOS. The PCOS status should be regarded as a predictor marker of cardiovascular risk, along with well-known cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC) therapy and orbital radiotherapy represent the classic medical management of Graves' ophthalmopathy, either used separately or in association. Because of the lack of response for classic therapy, in some patients new immunosuppressive methods have been tried, one of them is cyclosporine, an selective immunomodulatory drug. This study has proposed to compare short time administration of cyclosporine with administration of iv methylprednisolone and combined therapy (methylprednisolone - orbital radiotherapy). In this comparative and prospective study we followed 127 patients with Graves' ophthalmopathy divided in 4 groups, treated with iv methylprednisolone, associated therapy (GC+RxT), cyclosporine and a control group. All patients were concomitantly treated with oral antithyroid drugs. At 0, 3 and 6 months, the patients were subjected to Hertel exophthalmometry, orbital ultrasonography, TSHR antibody and thyroid-peroxidase antibody assessment and to clinical activity score (CAS) calculation. Comparing the means of each parameter assessed in all 4 groups, a significant decrease of exophthalmy and of extraocular muscle thickness was observed in each group, with a better effect of cyclosporine comparing to iv methylprednisolone, but with a lower effect of cyclosporine comparing to combined therapy. CAS improved significantly in all patients. Cyclosporine has a poorly effect on TRAb and ATPO in contrast with GC or combined therapy. [ABSTRACT FROM AUTHOR]

Oxidative stress may result from either overproduction of free radicals or from insufficiency of several antioxidant defence systems. Thyroid hormones have well-known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial. The aim of the study was to investigate the oxidant and antioxidant status in propylthiouracil-induced hypothyroidism and the effect of vitamin E supplementation on this experimental model. Materials and Methods. Thirty male Wistar rats were used in the study. Hypothyroidism was induced by administering Propylthiouracil (5mg/100g animal /day) for 30 days. Plasma was used to determine malondialdehyde (MDA), carbonyl proteins, SH groups, glutathion (GSH) and superoxide dismutase (SOD) while MDA, carbonyl proteins, SH groups and GSH were determined from the thyroid gland. Results. In plasma and thyroid homogenate of hypothyroid rats, the lipid peroxidation did not differ significantly from the control group. Carbonyl proteins levels increased significantly in serum and thyroid tissue of hypothyroid animals as compared to the control group. Antioxidant parameters SH groups, GSH and SOD levels did not show any significant changes. Vitamin E supplementation significantly increased carbonyl proteins levels and decreased SH, GSH and SOD levels compared with the Propylthiouracil treated group. Conclusions. Our study suggests an elevated reactive oxygen species which may be a result of increased oxidative stress. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is possibly the most common endocrinopathy of reproductive age, characterized by hyperandrogenism and oligomenorrhea. Additionally, approximately one-third to one-half of all women and adolescent girls with PCOS tend to fulfill many of the metabolic syndrome criteria, and many view PCOS as a premetabolic syndrome condition, predisposing to a high risk for cardiovascular disease. Endothelial dysfunction, impaired arterial structure, or proinflammatory markers are early features of atherosclerosis, and can be used as surrogate indicators of future coronary artery disease in women with PCOS. However, as the latest studies show, these symptoms are the result of deleterious effects that cardiovascular risk factors, in particular insulin resistance and obesity, produce on the vascular wall, rather than to the presence of PCOS per se. The relationship between hyperandrogenemia and the risk of cardiovascular disease is controversial and needs to be clarified. Further research is warranted to understand the pathogenesis of cardiovascular disease in PCOS, and to identify subtypes of PCOS in which the presence of cardiovascular risk factors may result in increased cardiovascular events, leading to high morbidity or mortality rates caused by cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction. Vitamin D deficiency has been proven to have a deleterious effect on bone remodeling and bone mineral density, by inducing secondary hyperparathyroidism. The lack of a present consensus on optimal serum 25(OH)D levels required for the preservation of physiologic bone metabolism renders its follow-up difficult. Materials and Methods. The cross-sectional study was performed on a sample of 69 healthy men aged 50-70. Serum 25(OH)D, total testosterone, sex hormone binding globulin, s-CTX (Crosslaps), and osteocalcin were assessed. BMD was measured by DXA at lumbar spine and hip levels. Statistical relationships between these parameters were calculated. Results. We found a significantly negative correlation between 25(OH)D and s-CTX (r = -0.30. p<0.08), but not between 25(OH)D and osteocalcin, although s-CTX correlated positively with osteocalcin (r = 0.49, p<0.001). Serum CTX was negatively correlated with lumbar BMD (r = -0.35, p<0.001), while osteocalcin was negatively correlated with total hip BMD (r = -0.26, p<0.01). Comparing mean s-CTX levels in insufficient and sufficient subjects at different cut-off points for 25(OH)D, significant differences appeared the strongest at 60 ng/ml. The percentage of 25(OH)D deficient or insufficient subjects was 50.7% at a 30 ng/mI cut-off point. Conclusions. The results of the present study confirm the benefit in maintaining a normal bone turnover offered by serum 25(OH)D in the upper normal range. The large percentage of patients with vitamin D insufficiency reinforce the necessity of a specific follow-up and of epidemiologic studies dedicated to our geographic area. [ABSTRACT FROM AUTHOR]

The article celebrates the life and work of professor Liviu Gozariu, who died in 2012.

Osteoblasts produce both osteoprotegerin (OPG) and Receptor Activator for Nuclear Factor B Ligand (RANKL), members of the tumor necrosis factor (TNF) super family that compete for the same receptor - RANK - expressed at the surface of osteoclasts, to play important roles in bone remodeling by controlling differentiation, activation and apoptosis of osteoclasts. Osteoprotegerin is secreted at different other sites such as endothelial and vascular smooth muscle cells, pulmonary or renal tissue, or the immune system. Hormones, cytokines and transcription factors, with osteotropic hormones playing a key role, control OPG synthesis. Thyroid hormones regulate bone turnover, as evidenced by important changes in bone turnover found in patients with thyroid dysfunction. In thyroid hormones excess, the increase in serum OPG is, probably, due to enhanced bone turnover, to compensate for excessive bone resorption. In hypothyroidism, the mechanisms are less clear, either cardiovascular changes or the low OPG kidney clearance or the increased TSH level being involved. In addition, OPG is held responsible for the development of endothelial dysfunction, an early stage of atherosclerosis progression, thyroid dysfunction being associated to increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

Noonan syndrome is a genetic dominant disease that presents a wide variety of clinical characteristics. Frequently, the syndrome is associated with some autoimmune diseases, especially with chronic autoimmune thyroiditis. We report the case of a 21 years old girl diagnosed with Noonan syndrome and autoimmune thyroiditis relatively late, at the age of 20. The diagnosis was suggested by a cluster of significant clinical elements: facial dysmorphism, short stature, moderate mental retardation. The hormonal profile and karyotype contributed to the final certainty diagnosis. At this moment she is under thyroid substitution treatment. [ABSTRACT FROM AUTHOR]

Adiposity is more and more incriminated as a risk factor for bone health, but studies do not allow a consensus regarding the relative influence of lean and fat mass on bone density. Our cross-sectional study aimed towards ascertaining their probable different and weight-independent effect. Body composition and bone mineral density was assessed in 244 healthy men aged 20-87, using dual X-ray absorptiometry. All clinical risk factors were recorded. Principal Component Analysis, MANOVA, and MANCOVA multivariate tests were used to detect independent predictors of BMD and collinearity patterns between variables. Weight, height, absolute lean mass, and absolute fat mass were collinear interchangeable variables. An eight-model multiple multivariate analysis identified weight, combined or not to the proportion of fat mass, to best explain the variation of bone mineral density in each of five bone areas measured. Clinical factors constantly associated to bone mass were also the patients' age and their history of fractures. Physical activity and thiazide diuretics treatment were inconstantly associated to bone density. We concluded that body composition achieves its effect on bone density in close relation to body weight, but also individually. Fat tissue proportion is an independent negative predictor of bone density, while lean tissue proportion is a positive one. Multicollinearity of variables allows us to rely only upon some anthropometric parameters, ignoring others. [ABSTRACT FROM AUTHOR]

Introduction: The link between bone mass and body composition is widely recognized, but the mechanism remains unclear. Most studies enrolled subjects irrespective of their body weight and only few works were selectively performed on healthy subjects with body mass index (BMI) within normal limits. Material and methods: We aimed to determine the relevance of body composition parameters to bone mass in healthy, young and non-obese Romanian volunteers (n=42) and in postmenopausal women (n=20) and to establish the effects of menopausal transition. Both bone mineral density (BMD) and body composition were assessed using whole-body dual X-ray absorptiometry (DXA). Outcomes: Despite normal mean BMI, large variability of the whole-body fat mass (FM) content was noted, ranging between 18.6-49.7% in women and 22-40.3% in men. Fat mass was not related to bone density; in contrast, BMD at all sites was positively associated to fat-free mass (FFM) in young nonobese women (r=0.34-0.53). In women, the trunk fat mass/leg fat mass ratio was significantly predicted by age (p=0.001), explaining about 20% of the pattern variability. Menopausal status appeared not to significantly influence whole-body fat or FM distribution. A tendency towards a higher trunk FM/legs FM ratio was observed after menopause, but lost after age-adjustment. Conclusion: In non-obese subjects, even of young age, the FM content and distribution is highly variable. FFM mass appears to be the main composition contributor to bone mass, at least in young, healthy, non-obese women. Menopause is not associated to major changes of whole-body fat and trunk adipose tissue, although a significant decrease in peripheral FM content and a tendency towards an age-dependent central redistribution of adiposity is noticed. [ABSTRACT FROM AUTHOR]

Hemorrhagic or ischemic pituitary apoplexy is a rare neuro-endocrine emergency, potentially leading to coma. Neuro-ophthalmic symptoms or complications are amongst the most prevalent clinical features at onset, especially in previously asymptomatic patients. Usually, permanent pituitary insufficiency of various degrees follows, implying long-term hormone substitutive therapy. Rarely, the association of pituitary apoplexy with diabetes insipidus has been noticed. We report the case of a young, apparently healthy 32-yearold man presenting with thunderclap headache, fever, optic chiasm compression, central diabetes insipidus and central thyro-gonadic insufficiency. Magnetic resonance imaging and neurosurgery revealed a clinically non-functioning macro-adenoma developing pituitary hemorrhage. One year after the apoplectic episode, complete recovery of diabetes insipidus and pituitary function was confirmed. [ABSTRACT FROM AUTHOR]

Hemorrhagic or ischemic pituitary apoplexy is a rare neuro-endocrine emergency, potentially leading to coma. Neuro-ophthalmic symptoms or complications are amongst the most prevalent clinical features at onset, especially in previously asymptomatic patients. Usually, permanent pituitary insufficiency of various degrees follows, implying long-term hormone substitutive therapy. Rarely, the association of pituitary apoplexy with diabetes insipidus has been noticed. We report the case of a young, apparently healthy 32-year-old man presenting with thunderclap headache, fever, optic chiasm compression, central diabetes insipidus and central thyro-gonadic insufficiency. Magnetic resonance imaging and neurosurgery revealed a clinically non-functioning macro-adenoma developing pituitary hemorrhage. One year after the apoplectic episode, complete recovery of diabetes insipidus and pituitary function was confirmed. [ABSTRACT FROM AUTHOR]

Klinefelter syndrome is the most known disorder of the sex chromosomes with a frequency of 1/600 male newborns. The authors present a rare case of Klinefelter syndrome (mozaicism) with multiple dysfunctions, Biermer anemia, unilateral renal agenesis and also they discuss the pathogenesis of these diseases, connected with Klinefelter syndrome. They emphasize the rarity of this type of Klinefelter syndrome (46XY/47XXY) associated with multiples somatic anomalies and endocrine complications. [ABSTRACT FROM AUTHOR]

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24-80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c-QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis. [ABSTRACT FROM AUTHOR]

Iodine plays an important biochemical role in human organism; its insufficiency produces disturbances in the synthesis of thyroid hormones and increases the volume of the thyroid gland. Iodine deficiency in pregnant women has severe consequences on maternal body and fetal development. The aim of this study was to determine the incidence of iodine deficiency in pregnant women from Cluj city and county. Urinary iodine levels were determined by the Sandell-Kolthoff method. A group of 100 pregnant women was studied. The results show a mean iodine concentration at the lower limit of the normal range (107.58 ± 91.16 μg/L), not correlated with the period of pregnancy. [ABSTRACT FROM AUTHOR]

Graves' disease is an autoimmune disorder characterized by various degrees of thyroid gland, eye and skin affection. We present the case of a 36 years old woman diagnosed with Graves' disease and infiltrative ophthalmopathy class IV according to Werner classification, non-responsive to Methylprednisolone antiinflammatory therapy and to irradiation. From anamnesis we mention Graves' disease's debut approximately one year ago, manifested by thyrotoxicosis features without evident ophthalmopathy. Antithyroid drug therapy was started at debut and maintained for eleven months. One month after antithyroid drug therapy cessation, the patient developed diplopia, periorbital edema, and proptosis. At that moment we decided to initiate intravenous Methylprednisolone therapy using a total dose of 3 grams, followed by oral corticotherapy in association with antithyroid drug therapy. One month later, when bilateral fat tissue hernia appeared in the external orbital angle, we decided to add orbital radiotherapy. In the absence of any evident clinical improvement, immunosuppressive treatment with Cyclosporine 5 mg/kg/day was chosen. Consequently, ,we obtained a significant reduction of eye proptosis, 4 mm at the right eye, and 3 mm at the left eye, a significant reduction of bilateral orbital fat tissue hernia, and no more diplopia. [ABSTRACT FROM AUTHOR]

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.

Previous clinical studies have suggested a positive correlation between serum insulin-like growth factor components and bone mass in both men and women with or without osteoporosis. The aim of the present study was to analyze the relationship between the skeletal levels of insulin-like growth factors and transforming growth factor-b1 and bone mineral density in a group of men and postmenopausal women in whom osteoporosis was diagnosed previously. Bone matrix extraction was achieved by passive dialysis against tetrasodium EDTA-guanidine-HCL. IGF's were quantified by radioimmunoassay. TGF-b1 was assessed by a specific enzyme-linked immunoassay. No correlation between BMD and the concentration of IGF-I, IGF-II and TGF-b1 in bone matrix was detected in either men or postmenopausal women with osteoporosis. In addition, circulating growth factors levels failed to be associated with the concentration of IGF-I, IGF-II and TGF-b1 in the skeleton. Thus, our study provides no evidence for a major role of bone matrix IGF's or TGF-b1 as determinants of bone mass in men or postmenopausal women with osteoporosis.