The Wnt/ß-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity.

BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/ß-catenin signalling pathway (WßcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WßcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS: The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS: Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION: CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

Multiple Causes of Hyponatremia: A Case Report.

OBJECTIVE: To present a case with 4 different potential causes of hyponatremia. CLINICAL PRESENTATION AND INTERVENTION: The patient presented with the following symptoms: nausea, vomiting, diarrhea, and dark urine after drinking large amounts of fluids that included alcohol and caffeine. Laboratory, microbiological, and morphological examinations revealed the existence of severe hyponatremia and acute poststreptococcal glomerulonephritis. The patient developed acute symptomatic seizures and coma. Gradual normalization of the sodium level led to a recovery of consciousness. CONCLUSION: Treatment with hypertonic sodium, fluid restriction, and antibiotics led to a complete recovery. In the case of multiple causes of hyponatremia, it is necessary to treat all causes.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity.

BACKGROUND AND OBJECTIVES: Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD: This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS: All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION: The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

The influence of bone mineral density and bisphosphonate therapy on the determinants of oral health and changes on dental panoramic radiographs in postmenopausal women.

OBJECTIVES: The aim of this study was to assess the determinants of oral health including the number of decayed, missing, and filled teeth (DMFT) and periodontal indices in postmenopausal women with osteoporosis, osteoporosis treated with bisphosphonate therapy, and control group and to examine the correlation between dental panoramic indices (Mental Index-MI, Mandibular Cortical Index-MCI) and bone mineral density in these three groups of patients. MATERIALS AND METHODS: The presented non-interventional study involved 120 postmenopausal women: women with osteoporosis (O) (n = 45), women with osteoporosis treated with bisphosphonates (OBP) (n = 45), and control group (C) (n = 30). DMFT, plaque, gingival and papilla bleeding index, pocket depth, clinical attachment loss, and the presence of periodontitis were evaluated for each patient. MI and MCI of all participants were measured on a dental panoramic radiograph. RESULTS: Group OBP showed significantly higher gingival, bleeding index and deeper pocket depth than C and/or O group. No significant differences were found in MI (p = .303) or MCI (p = .06) in all the examined groups. Also, there were no significant differences between the three groups in the presence of periodontitis as well as in the DMFT index. CONCLUSION: BP therapy could have a negative influence on periodontal health. Further, MI and MCI are not precise diagnostic tools for diagnosing low BMD in postmenopausal women. CLINICAL RELEVANCE: BP therapy could have a negative influence on the determinants of oral health in postmenopausal women with osteoporosis.

Pituitary Abscess with Unusual Clinical Course

The aim is to present unusual clinical course and magnetic resonance imaging (MRI) features of pituitary abscess. A 59-year-old man presented with fever, polyuria, polydipsia and marked weight loss within the last two months. Basic endocrinology tests revealed the presence of anterior pituitary dysfunction, associated with central diabetes insipidus and increased levels of inflammatory markers. The presence of expansile sellar lesion, showing restricted diffusion signal pattern compatible with acute pituitary pyogenic abscess was found on MRI. Regression of pituitary abscess was obvious during the next few weeks of parenteral antibiotic treatment. Adequate substitution treatment with L thyroxine, hydrocortisone, testosterone and desmopressin was achieved. Seventeen months later, clinical deterioration associated with recurrent pituitary abscess was confirmed on MRI. Abscess regression was obvious again after conservative treatment. However, control MRI study performed three years after initial scanning revealed the presence of pituitary tumor, most consistent with macroadenoma. Surgical intervention was ordered. Histologic evaluation indicated the presence of fibrotic changes, associated with granulation tissue and rare cellular elements, compatible with chronic inflammation. To the best of our knowledge, there are no studies in the literature describing such a pattern of chronic evolution of pyogenic pituitary abscess with consequent chronic inflammatory changes with granulation tissue proliferation, mimicking macroadenoma.

Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.

Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet--a case report.

INTRODUCTION: Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. CASE REPORT: We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 µg of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. CONCLUSION: Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.

Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia.

Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment.

Vitamin D and Dysfunctional Adipose Tissue in Obesity.

Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r = -.61, P < .01), while a positive association with adiponectin concentrations was found (r = .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies.

The influence of hyperprolactinemia on coagulation parameters in females with prolactinomas.

INTRODUCTION: Currently there is little information on the effects of prolactin (PRL) on the coagulation and fibrinolytic systems. OBJECTIVE: The aim of this study was to evaluate the effects of hypeprolactinemia on the parameters of the hemostatic system and activation of the coagulation system. METHODS: We studied PRL levels, body mass index (BMI), values of activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), D-dimer level, von Willebrand factor antigen (vWFAg) and fibrinogen in 15 young female patients with microprolactinomas before and after therapy and in 15 healthy female controls. RESULTS: As expected, pretreatment PRL levels were significantly higher in patients than in controls (140.90 +/- 42.87 vs. 12.53 +/- 4.05 ng/ml; p < 0.001). PT, although still in the normal range, was prolonged in patients with hyperprolactinemia as compared to the control group (13.53 +/- 1.39 vs. 12.65 +/- 0.53 s; p = 0.03) and normalized after therapy (12.69 +/- 0.65 vs. 12.65 +/- 0.53 s; p = 0.88). TT, although in normal range, was significantly shorter in the hypeprolactinemic patients than in the controls (14.34 +/- 4.52 vs. 17.21 +/- 1.35 s; p < 0.025) and after treatment remained significantly shorter than in the controls (15.17 +/- 1.55 vs. 17.21 +/- 1.35 s; p < 0.0001). D-dimer values before treatment in the patients with hyperproplactinemia were above the normal range (239.47 +/- 107.93 vs. 131.27 +/- 50.64 ng/ml, p = 0.002) and decreased to normal values after therapy (239.47 +/- 107.93 vs. 146.60 +/- 39.15 ng/ml; p < 0.001). D-dimer levels correlated with PRL (r = 0.30) and the change in serum D-dimer values significantly correlated with the change in PRL levels during therapy (r = 0.62). aPTT, vWFAg and fibrinogen were similar in patients and controls. CONCLUSION: In our study, increased thrombin generation that resulted in elevated D-dimer levels may be one of the contributing factors to the prethrombotic state in patients with hyperprolactinemia.

[The quality of life in patients with diabetes mellitus type 2].

BACKGROUND/AIM: Through its vrious activities, World Health Organization (WHO) contributed to increasing the understanding of the concept of quality of life. People with diabetes have a lower quality of life than people without chronic illnesses. The aim of this study was to examine the differences in the quality of life, related to health, in patients with diabetes mellitus (DM) type 2 by age, gender and type of therapy. METHODS: We performed a cross-sectional study at the outpatient department of the Clinical Center in Novi Sad and the Health Center Ruma-General Practice. The group consisted of 90 patients with DM type 2, 41 men and 49 women. The age of respondents was from 40 to 80 years and they were classifed into four groups according to the ten-year age intervals. We applied WHO Quality of life questinnaire--BREF 100 composed of four domains: physical health, psychological health, social relationships and environment. The general questionnaire asks questions about socio-demographic data, duration of diabetes, the last value of blood glucose and glycosylated hemoglobin, training for self-control and its implementation, informing patients about their disease, therapy and its impact on daily activities and the presence of comorbidity. In statistical analysis the following tests were used: Student's t-test, F-test, ANOVA (one way). RESULTS: The average duration of DM type 2 was 11.2 +/- 9.2 years. Most of the patients (76%) were trained to self-control and 91% received enough information about their disease. Oral hypoglycemic preparations were used by 49%, insulin by 21%, and oral drugs and insulin by 29% patients while 1% were on a special regime of a diet therapy. Daily activities were performed without difficulties by over 29%, with some difficulties by 41% and 30% of patients who could not perform daily activities. The patients with DM type 2 had significantly lower scors in all 4 domains of quality of life (physical health, psychological health, social relations, environment). The biggest influence was on physical domains (51.31). Education level had an imact on physical and psychological domains. Comorbidity was found in 83% of the respondents. The most common were: arterial hypertension (63%), chronic cardiovascular disease (46%), neuropathy (23%), impaired vision 24%, elevated blood lipids (39%) and amputation of toes or feet (2.2%). The average value HbA1c in the group with comorbidity was 8.47% and in the group without comorbidity 6.46%. The subjects with comorbidity had low quality of life assessment in relation to the group without comorbidity: the domain of physical health (45.64 vs. 79.66), psychological health (50.3 vs. 76.86), social relations (52.97 vs. 75.46) and environment (52.7 vs. 75.06). CONCLUSION: Diabetes mellitus type 2 has negative influence on the quality of life. It contributes to the presence of comorbidity. The occurrence of comorbidity was associated with higher glucosylated HbA1c values. There was no difference in the assessment of quality of life regarding gender, age, or the type of therapy used. The quality of life was assessed as low in patients with comorbidity. However, certain personality characteristics play a decisive role in self-evaluation.

[Hormone replacement therapy and cardiovascular risk in postmenopausal women].

Five years after the menopause, we can see the increase in cardiovascular risk due to prolonged deficiency of ovarian hormones. These risks are the same or even more severe than those in men within the same age group. The basic influence of normalizes those disturbances. In 2002. published data from a WHI study show an increase in cardiovascular risk during the first year of hormone replacement therapy with no protective effect. The most recent published data from WHI study show positive effects of hormone replacement therapy, within postmenopausal women younger than 65 years. Those women had significantly reduced calcifications on coronary vessels The American Association of Clinical Endocrinologists and the estrogens can be genomic and non genomic. Estrogens influence endothelia and smooth muscle wall of arterial blood vessels, metabolism of lipoproteins and induce the metabolic syndrome. Hormone replacement therapy partially or completely International Menopause Society proclaim that the hormone replacement therapy can prevent cardiovascular diseases and slow down the progress of atherosclerosis. The aim of ongoing KEEPS is to investigate the preventive effect of the hormone replacement therapy on blood vessels, in early postmenopausal period (women younger than 60 year). This study should be valid enough to define new clinical knowledge about the hormone replacement therapy and cardiovascular risk.

[Body composition and bone mineral density of prepubertal boys involved in different kinesiologic treatments].

INTRODUCTION: It is well known that physical activity has an anabolic effect on the bone tissue. But there is a lack of information about the effect of intensive physical activity in childhood, particularly at the prepubertal stage. The type, frequency, intensity, and duration of activity that best produce the desired increases in mass and strength of human bones have not yet been well determined. MATERIAL AND METHODS: To examine the influence of different kinesiological treatments on body composition and bone mineral density we studied a group of prepubertal boys at the starting phase of their peak bone mass acquisition. 90 healthy prepubertal boys took part in this study. The sport group consisted of 28 swimmers (aged 10.80.8) and 32 soccer players (aged 10.70.5), who had been training their chosen high-level sport activity for at least 1 year (8-12 h per week for swimmers, 10-15 h per week for soccer players). 30 boys (aged 11.2 +/- 0.7) doing 1.5 h per week of physical activity in school served as a control group. Bone mineral density measurements of the left and right calcaneus were done by ultrasound densitometer "Sahara". The body composition was assessed by Body Fat Analyser "BES 200 Z". RESULTS: There were significant differences between soccer players and control group as regards fat mass and bone mineral density (p<.01). Besides, significant differences were determined between a group of swimmers and control group as regads fat mass (p<.03), while the differences in bone mineral density were not very obvious (p<.67).

[Bone metabolism during substitution therapy of primary hypothyroidism].

INTRODUCTION: The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. MATERIAL AND METHODS: In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type l-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. RESULTS AND DISCUSSION: A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p = 0.000024), CL (p = 0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p = 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p = 0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. CONCLUSION: It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long-term prospective studies in patients on replacement l-thyroxine therapy.