ACTA ENDOCRINOLOGICA (BUC)

Leptin is much more than a simple sensor of body fat levels. Its biological activities, include angiogenesis, osteogenesis and modulation of the immune and reproductive systems. There are no reports on fluctuations of the level in normal human functional glandular epithelium during the menstrual cycle. Objective. We aimed to determine the expression level of the leptin receptor by immunohistochemistry and to correlate this with estrogen and progesterone receptor levels in normal endometrial tissue throughout the menstrual cycle. Study design. Thirty-seven paraffin wax blocks of biopsy specimens of histologically normal endometrium were evaluated and classified according to the stage of the menstrual cycle during the 2004–2006 period. Results. The OB-R level underwent fluctuations during the menstrual cycle in the different tissue compartments; these were most marked in the functional glandular epithelium and during the proliferative stage. OB-R levels were correlated positively with the expression levels of estrogen and negatively with those for progesterone receptors, suggesting that these steroids modulate the expression of OB-R in vivo. Conclusion. This finding underscores the importance of considering the menstrual cycle stage for studies seeking possible impacts of the OB-R on reproductive pathology, because its expression level varies with the hormonal environment.

Background. In vitro studies of the changes about osteoblastogenesis and adipogenesis potential of BMSCs were not clear. As it is the critical pathway for osteogenic differentiation and bone formation, whether or not Wnt/β- catenin signalling is involved in the changes of osteogenic and adipogenic potential of BMSCs and participates in bone content decrease of ovariectomized (OVX)osteoporosis rats has been rarely reported. Material/Methods. BMSCs from femurs of ovariectomzed rats were isolated and cultured in vitro. The proliferation potential of BMSCs was analysed by CCK-8 assays . Osteoblastic and adipogenic differentiation potential of the BMSCs was assessed by ALP activity assay, Alizarin red S staining, Oil red O staining and RT-PCR analysis. Results. The results demonstrated that BMSCs from bilateral ovariectomization rats were endowed with lower proliferation and osteoblastic differentiation potential but higher adipogenic potential than the control group in vitro. In addition, β-catenin was found to have been decreased in OVX BMSCs, indicating that Wnt/β-catenin signalling pathways were suppressed in OVX BMSCs . Conclusions. Results suggested that changes in the Wnt canonical signalling pathway may be related to imbalances of osteogenic and adipogenic potential of BMSCs, and this may be an important factor related to bone content decrease in ovariectomized osteoporosis rats.

Context. The prevalence of patients with concomitant heart failure (HF) and diabetes mellitus (DM) is high. Objective. To analyze the role of NT-pro-BNP levels in the evaluation of diabetic patients with heart failure. Design. Retrospective comparative cohort study. Subjects and Methods. A total of 174 patients admitted to our Cardiology Department, previously diagnosed with HF, were enrolled. Among these patients, 47.7% had DM. HF was defined according to the 2016 ESC criteria. The NT-pro BNP levels above 126 pg/mL indicate a high probability of heart failure. Results. In diabetic patients there were significant correlations between NT-pro-BNP values and the following parameters: hemoglobin (rho=-0.28, p=0.01), hematocrit (rho= -0.27, p=0.014), total cholesterol (rho= -0.21, p=0.048), triglycerides (rho= -0.283, p=0.01), ejection fraction (rho= -0.465, p<0.0001), end-diastolic volume (rho= 0.253, p= 0.026), end-systolic volume (rho= 0.29 p=0.01). Only the following 3 parameters: ejection fraction (p= 0.0009), hemoglobin (p= 0.0092) and triglycerides (p= 0.0380) were independent predictive factors for elevated NT-pro-BNP values. Conclusion. In diabetic heart failure patients, the value of NT-pro-BNP holds a pivotal role in the evaluation of their overall status, facilitating the establishment of correct management and follow-up.

Context. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Context. Spontaneous muscle infarction is a rare complication of diabetes mellitus, mainly affecting women and patients with long-lasting type 1 diabetes. Objective. This report is aimed to describe the case of a patient with type 1 diabetes and diabetic nephropathy in whom a severe deterioration of renal function was triggered by a muscle infarction. Subject and Methods. Subject of the study was a 33-years-old woman with an 18 years history of type 1 diabetes mellitus, proliferative diabetic retinopathy, nephropathy at stage 3 chronic kidney disease, somatic sensory-motor polyneuropathy and autonomic neuropathy. Results. The patient presented with severe pain and dysfunction of the left thigh without prior trauma plus progressive deterioration of the renal function. Nuclear magnetic resonance of the thigh showed inflammatory changes in the external vastus with hyperintensity on T2 sequence and edema of the subcutaneous cellular tissue. After other possible etiologies were ruled out, a clinical diagnosis of spontaneous muscle infarction was established. The patient needed hospital admission for two months, during which the renal function worsened until she required hemodialysis. No other possible triggers of kidney injury were identified. Conclusions. Up to our knowledge, this is the first described case where muscle infarction is suspected to have caused exacerbation of an existing chronic kidney failure. Monitoring the renal function should be considered in patients with diabetic nephropathy presenting with this rare complication of diabetes.

Context. Postmenopausal women are at risk of developing primary hyperparathyroidism (PHPT) and the underlying\r\ndisturbance in calcium homeostasis is suspected to have been established for some time prior to diagnosis.\r\nObjectives. Pre-menopausal women with disturbance in calcium homeostasis suggesting PHPT have been evaluated during\r\nmenopausal transition regarding associated morbidity.\r\nDesign and subjects. Premenopausal women, 40 to 50 years of age, were screened with parameters of calcium homeostasis in\r\nconjunction with routine mammography during 2002-2003. Those who fulfilled preset criteria of mild PHPT (cases) (n=173) were matched to controls (n=193). The pre/perimenopausal\r\nwomen were investigated for the prevalence of PHPT in association with skeletal changes, morbidity and impact on\r\nquality of life (base-line data already published). They have now been re-evaluated regarding different health aspects after three years follow-up.\r\nResults. The cases still had lower bone mineral density (BMD) in total hip, femoral neck and distal third of radius than controls (p<0.05) after three years followup. Time of follow-up, menopausal status, and weight affected BMD independently.\r\nConclusion. Middle-aged women with mild disturbances of calcium homeostasis suggesting early PHPT, had lower BMD in the hip and radius, but the decline in BMD was not accelerated during menopausal transition.

Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is common in the community. The most important clinical manifestation of G6PD deficiency is acute hemolytic anemia due to oxidative stressors. Diabetes Mellitus (DM) can precipitate hemolysis in patients with G6PD deficiency. Here, we described a 15-year-old male with newly diagnosed type 1 DM (T1DM) and unknown G6PD deficiency who suffered from hemolytic anemia during normalization of blood glucose. On admission, the patient did not have ketoacidosis. After the patient's blood sugars were regulated with insulin therapy, he presented five days later with hemolytic anemia. The cause of hemolytic anemia was G6PD deficiency. The patient had no previous episodes of hemolysis and had no relevant family history. Hypoglycemia did not occur during blood glucose regulation. The return of blood sugar to normal after a long period of hyperglycemia was thought to be the possible cause of hemolysis. In conclusion, G6PD deficiency should be considered when there is an episode of hemolysis in newly diagnosed children and adolescents with T1DM, especially in the absence of ketoacidosis and hypoglycemia.

Context. In addition to traditional risk factors for cardiovascular diseases, there are new risk factors with potentially relevant prognostic, such as vitamin D deficiency. Objective. The study aims to analyze the relationship between vitamin D deficiency and the occurrence of cardiovascular disease, in patients who already have at least one cardiovascular risk factor. Design. It is a prospective, observational study. Follow- up time was 24 months. Subjects and methods. A total of 77 patients were included in the study, aged over 18 years, who had at least one cardiovascular risk factor. Their vitamin D levels were measured and they were monitored for a period of 2 years, in order to see which one developed cardiovascular diseases. Results. Of the 77 patients, 56 (72.7%) had serum deficient levels of vitamin D and the mean serum level was 16 ng/mL (± 8.6 ng/mL). Statistically significant differences were observed only in the case of dyslipidemia (p=0.0334). The evolution to cardiovascular disease occurred in 39 of the cases (50.6%). The only independent risk factors for progression to cardiovascular disease demonstrated in this study were serum vitamin D (OR = 0.9024, 95% CI: 0.83- 0.97 and age (OR = 1.1313, 95% CI: 1.05-1.21). Conclusion. The results shows that patients with cardiovascular risk factors and advanced age are at a higher risk of developing cardiovascular disease, if they also have vitamin D deficiency.

Background. Myocardial involvement is frequent in patients with systemic lupus erythematosus (SLE), and its early detection assures the prognosis improvement. Objective. To assess the NT-proBNP levels and its correlation with systolic longitudinal performance, during exercise testing in a SLE population Subjects and Methods. The study included 30 SLE patients (80 % females), with a mean age of 44.8 ± 9.91 years. All subjects were submitted to an echo Doppler examination, including the determination of the global longitudinal strain (GLS). Also, they performed a cardiopulmonary exercise testing (CPE) on cycloergometer, assessing the peak oxygen uptake. Venous blood samples were taken and NT-proBNP levels were determined before exercise, at peak effort and two hours after exercise. Results. The left ventricular ejection fraction was normal but GLS was low in SLE patients ( -16.96 ± 3.12%, vs. -19.5 ± 3.05% normal range) and much lower in those with diastolic dysfunction (-14.5 ± 2.3% vs. - 19.2± 1.85%, p=0.0014). During CPE, the patients performed a mean 71.96% ± 13.9% of predicted VO2 max. The mean values of NT-proBNP were: 186.84 ± 186.8 pg/mL at rest, 221.68 ± 245.76 pg/mL at peak effort and 412.48 ± 400.28 pg/mL post effort. No correlation was registered between GLS and peak VO2. We found a negative correlation between GLS ant NT-proBNP at peak effort (r = -0.508) and post exercise (r=-0.623). Conclusion. The exercise NT-proBNP levels can be used together with GLS for an early detection of systolic dysfunction in SLE patients.

Introduction. Considering the very important role of adiponectin and leptin in\r\natherogenesis, it is important to study their relationship with other important factors in\r\nestablishing the cardiometabolic risk: hyperglycemia and serum lipids.\r\nPatients and Methods. There were studied 79 subjects (s), aged 59? 9 years, divided\r\ninto 3 groups according to body mass index (BMI): group I with BMI<25 kg/m2 - 19 s,\r\ngroup II with BMI 25-30 kg/m2 - 30s, and group III with BMI >30 kg/m2 - 30 s. In all\r\nsubjects the plasmatic levels of adiponectin, leptin and other cardiometabolic risk factors:\r\nblood glucose, total cholesterol, triglycerides, high density cholesterol, low density\r\ncholesterol were measured.\r\nResults. Considering the values of adiponectin and leptin in the three groups,\r\nadiponectin was significantly increased (14355?9120.40 vs 5889.167?6278.963 ng/mL,\r\np=0.015) and leptin significantly decreased (7212?7428.45 vs 9235.81?10988.66 pg/mL,\r\np=0.03), in group I in comparison with group II+III. Adiponectin and leptin were not\r\nsignificantly different in subjects with fasting glucose less or more than 110 mg/dL and the\r\nsame insignificant difference was registered for both adipokines between diabetic and non\r\ndiabetic subjects. Considering the plasma lipid fractions, it was registered an inverse\r\nsignificant correlation between adiponectin and total cholesterol, respectively LDL\r\ncholesterol, and a positive correlation with HDL cholesterol; leptin was inversely correlated\r\nwith HDL cholesterol, but not with LDL cholesterol or total cholesterol.\r\nConclusion. In the present study, the plasmatic values of adipokines (adiponectin and\r\nleptin) were correlated only to the BMI values (obesity) and respectively to the lipidic\r\nfractions. No correlation was registered with diabetes or impaired fasting glucose.