ACTA ENDOCRINOLOGICA (BUC)

Context. Thyrotoxicosis is an important cause of secondary osteoporosis, but the extent of bone loss and its\r\nreversibility with therapy have not been clearly determined yet.\r\nObjective. We assessed the impact of thyrotoxicosis on bone mineral density (BMD) and the recovery of bone loss with\r\ntherapy. We also tested, in this context, the hypothesis that low TSH levels, even within reference range, increase fracture risk.\r\nDesign, Subjects and Methods. In this retrospective study we compared 78 women with thyrotoxicosis and osteopenia /\r\nosteoporosis (TX ? study group), with 82 age matched, euthyroid women with primary osteopenia /osteoporosis (C-control group). All patients had a baseline and at least one follow-up assessment of lumbar spine BMD by dual-emission X-ray absorptiometry (DXA) and thyroid function (thyrotropin ? TSH and free thyroxine ? fT4, measured by electrochemiluminescence immunoassay).\r\nResults. Mean BMD and T scores were similar at baseline (0.764 g/cm2, -2.50 SD in the TX group 0.747 g/cm2, -2.59 SD\r\nin C group); 17 thyrotoxic patients and 17 patients with primary osteoporosis had previous fractures. Both groups showed a significant BMD increase with therapy, over a similar period of time (TX ? mean 10.38 months; C ? 10.74 months). BMD gain was significantly higher in the study\r\ngroup (p = 0.04). In hyperthyroid patients, the best predictor for bone density increase was the TSH raise, while in controls the main determinant was treatment duration.\r\nConclusions. In comparison to primary osteoporosis, bone loss recovery rate with appropriate therapy is higher in\r\nthyrotoxicosis, confirming its contribution to the pathogenesis of osteoporosis.

Background. The pathogenesis of pre-eclampsia involves inflammation, endothelial\r\ndysfunction and enhanced oxidative stress. Interleukin (IL)-6 is a major pro-inflammatory\r\ncytokine, while leptin is released in large amounts by the adipose tissue, but also by placenta.\r\nAim. The present study aims to evaluate total maternal serum leptin and IL-6 levels in\r\npre-eclampsia compared to normal pregnancy and non-pregnant status.\r\nMethods. We enrolled 65 women in a transversal study; pre-eclampsia was diagnosed\r\nin 25 (group 1), 25 women had a normal pregnancy (group 2), while in 15 pregnancy was\r\nexcluded. Groups were matched for chronological and gestational age and body mass index\r\n(BMI) accordingly. Total serum leptin and serum IL-6 were determined using ELISA, after\r\nan overnight fasting period of at least 12 hours.\r\nResults. Both leptin and IL-6 concentrations were significantly higher in women in the\r\nthird trimester of pregnancy developing pre-eclampsia compared to normotensive pregnant\r\nwomen (p=0.001). Normal pregnancy was characterized by increased serum leptin levels\r\n(p=0.001) as well as increased IL-6 levels (p=0.001) in comparison to non-pregnant status.\r\nIn women with pre-eclampsia, leptin was positively and significantly correlated with\r\ndiastolic blood pressure (r=0.45, p=0.02), proteinuria (r=0.48, p=0.01) and uric acid values\r\n(r=0.39, p=0.04) and inversely related to HDL cholesterol levels (r=-0.64, p=0.0001).\r\nLikewise, IL-6 was positively related to systolic and diastolic blood pressure (r=0.41,\r\np=0.008 and r=0.60, p=0.00003, respectively), proteinuria (r=0.38, p=0.01) and uric acid\r\nvalues (r=0.43, p=0.004). However, leptin had no correlation with pregnancy outcome in\r\nwomen with or without pre-eclampsia. In contrast, IL-6 was negatively correlated with both\r\nfetal birth at weight (r=-0.35, p=0.02) and Apgar score (r=-0.38, p=0.01).\r\nConclusions. In conclusion pre-eclampsia associates significantly increased serum\r\nleptin concentrations and IL-6 production compared to normal pregnancy. In contrast to\r\nleptin, IL-6 may predict pregnancy outcome (fetal birth weight and Apgar score) in women\r\nwith pre-eclampsia.

Background. Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. Objective. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. Setting. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. Methods. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. Main outcome measure. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. Results. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. Conclusions. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

Background. We know that mortality had increased in diabetic patients with COVID-19 pneumonia. The aim of this study was to compare the mortality and inflammation parameters difference in critically ill COVID-19 patients according to their admission HbA1c levels and diabetes mellitus status. Secondary aim was to evaluate the effect of the first week hyperglycemic episode frequency on mortality. Methods. Critically ill COVID-19 patients who were tested for HbA1c levels on ICU admission were analyzed retrospectively. Results. Of 218 COVID PCR(+) patients, 139 met the inclusion criteria in study period. The median age was 67[57-76] years and 55(40%) of them were female. Seventy-six (55%) of the patients required invasive mechanical ventilation (IMV). The IMV requirement was higher in diabetic patients (p=0.01). When the groups were compared in terms of inflammatory parameters no significant difference was found except for admission and first week’s highest fibrinogen levels (p=0.02 and p=0.03, respectively). In multivariate analysis, fibrinogen levels were not determined as a risk factor for mortality. Overall ICU mortality was 43% (60/139). In group-1 23(37%), in group-2 27(57%), and in group-3 10(34%) patients had died. There was no statistically significant difference between groups in terms of mortality (p=0.05). Records of 96(69%) patients revealed there were more than five glucose readings over 180mg/dL during the first week. Mortality was higher in patients with more frequently hyperglycemic recordings (p=0.03). Conclusions. There was no significant mortality and inflammatory parameters difference in patients with and without diabetes. However, more than five glucose readings over 180mg/dL during the first week were found with increased mortality.

Background. Patients with type 2 diabetes mellitus (T2DM) have a higher risk of developing obstructive sleep apnea (OSA) compared to the general population. Our study aims to analyze the usefulness of the STOP-BANG score, tool which was not yet validated in patients with diabetets, as a tool that estimates the severity of OSA, in patients with T2DM. Methods. 120 patients, who answered the STOPBANG questionnaire and underwent polysomnography, were included in the study. The patients were divided into 3 groups, depending on the severity of OSA, defined by the apnea/hypopnea index (AHI). Results. A significant percentage of participants (42.1%) had a severe form of OSA (AHI ≥30) and a high percentage of subjects had a STOP-BANG score ≥5 (58.7%), equivalent to a severe form of the disease. The STOP-BANG score increased proportionally with AHI (p<0.001). The area under the ROC curve for the STOP-Bang score indicated an optimal cut-off value of 4.5, with a sensitivity of 88.2% and a specificity of 62.9% (p <0.001), STOP-BANG score ≥5 being an independent predictor for severe OSA in patients with T2DM. Conclusions. The STOP-BANG score can be used in patients with diabetes to detect severe OSA in order to establish appropriate therapeutic measures.

Context. Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. Objective. We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. Subjects and Method. We conducted a crosssectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot’s arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. Results. RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. Conclusions. RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Context. Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. Objective. We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Design. We conducted a cross-sectional casecontrol study for the period of 2008-2012. Subjects and methods. Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. Results. We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found – increased deceleration time and decreased e/a tric ratio. Conclusions. In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.

Introduction. The aim of this study is to appreciate the visual and endocrine outcome and to determine the factors that may influence the outcome of patients with pituitary apoplexy. Material and Methods. Between January 2006 and March 2012, 81 pituitary tumors were treated at “N. Oblu” Clinical Emergency Hospital in Iasi. Investigations of 22 of these cases met the criteria for pituitary apoplexy (17 cases of non-secreting pituitary adenomas and 5 cases of secreting tumors (4 GH secreting adenomas with acromegaly and 1 prolactinoma). Twenty one patients underwent surgery. The mean follow-up duration was 21 months. Results. Distribution between sexes was 1:1, with a mean age of 55.0 years. In all cases pituitary apoplexy emerged in patients with macroadenomas (>1cm). 77.27% presented decreased visual acuity, cranial nerve palsy was found in 45.45%. Visual acuity improved after surgical decompression best results being obtained in patients operated within first 7 days from onset (p=0.005); 80% recovered the CN palsy after surgery (p=0.005), with no relation to delay of surgery (p=0.26) or cavernous sinus invasion (0.095); 18.18% presented with pituitary deficiency and maintained it after surgery, the rate of new pituitary deficiency was 27.77% significantly higher in patients operated using craniotomies (p=0.001). Conclusions. Clinical apoplexy emerged in patients with macroadenomas unrelated to the tumor type. Early surgical decompression (< 7 days) and high dose corticoids represent the main therapeutic approach for obtaining good recovery of visual function. CN palsy has a good prognostic not being related to the delay of surgery. Pituitary dysfunction at presentation is irreversible and has a high occurrence after surgical decompression, requiring lifelong hormone replacement.

Introduction. Salusins are multifunctional endogenous peptides shown in human and rat tissues. Serum salusin α level is decreased in coronary artery disease and lack of salusin α enhances coronary atherosclerosis. Hypothyroidism is a chronic inflammatory disease that has a high risk of developing cardiovascular disease. Here we aimed to search the relationship of overt hypothyroidism and subclinical hypothyroidism with salusin α and other inflammatory markers, also the effect of L-thyroxine treatment on these findings. Material and Methods. 32 patients with overt hypothyroidism taking L-thyroxine treatment, 18 patients with subclinical hypothyroidism without treatment and 25 healthy patients as control group were included in the study. Serum salusin α, TNF α, sCRP, glucose, insulin and lipid levels were tested for all groups and results were evaluated with SPSS statistical analysis method. Results. HDL, sCRP, salusin mean values were statistically significantly different in all 3 groups. HDL level was statistically significantly higher in control group compared to treatment group. sCRP level was higher and salusin level was lower in both treatment and non-treatment hypothyroidism groups compared to control group. When treatment and non-treatment hypothyroidism groups were compared, there was no statistically significant difference for salusin α, but HDL level was high and insulin level was low statistically significant in treatment group. Conclusions. Salusin α that is shown to be protective for coronary artery disease and hypertension, is found to be significantly low in hypothyroidism, thus it is a marker that increases the cardiovascular disease risk in this specific patient group.

Objective. To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). Study Design. Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. Results. Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18–166) and 51 IU (20–114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. Conclusion. T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.