ACTA ENDOCRINOLOGICA (BUC)

Context. Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. Objectives. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. Subjects and Methods. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. Results. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Conclusion. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.

Introduction. Pulmonary hypertension (PHT) is a quite frequent echocardiographic finding in hyperthyroid patients and it regresses slowly under therapy with thiamazol.\r\nAim. The aim of the study was to follow the evolution of PHT over a period of a year, in two groups of hyperthyroid patients.\r\nMaterial and Methods. We followed up two groups of patients: one consisted of patients with chronic Graves Basedow\r\ndisease, some of them with good response to antithyroidian treatment and some other patients with repeated episodes of\r\ndecompensation despite medical therapy. The second group contained new diagnosed cases, a supgroup of patients with overt hyperthyroidism and one with subclinical forms. All 4 subgroups were followed over a period of 12 months. These subjects underwent thyroid hormone determinations and echocardiographic examination at 0, 1, 3, 6 and 12 months.\r\nResults. Our study group consisted of 92 patients with hyperthyroidism of different etiologies. None of the subjects had pulmonary or cardiovascular diseases severe\r\nenough to cause PHT by itself. We determined the presence and severity of pulmonary hypertension at the initial visit and followed its evolution at each scheduled visit in all four subgroups. All patients got antithyroidian therapy with thiamazol, but some chronic cases, with episodes of exacerbation, needed adjustments of their initial treatment. We noticed that PHT appeared in a higher percent and was more severe in the patients with severe hyperthyroidism or in the chronic cases with poor therapeutic response. We observed after some months a tendency to regression in\r\nthe well controlled patients or in those with subclinical disease.\r\nConclusion. The duration and severity of hyperthyroidism had a strong influence on the evolution of pulmonary hypertension in our patients.

Introduction. The definition of severity and activity of Graves' ophthalmopathy (GO)comprises different parameters.\r\nThe aim of this study is to select the most appropriate severity and activity criteria, respectively scores and to investigate a possible correlation among them.\r\nSubjects and methods. The study included 51 patients with GO (43 females, 8 males), mean age 46.8?11.2 years. The patients were evaluated by: clinical exam, laboratory\r\nparameters (TSH, FT4, FT3, thyroid autoantibodies) and imagistic means, performed in selected cases (CT or MRI).\r\nResults. The GO activity was assessed by the clinical activity score (CAS). We quantified the EUGOGO severity criteria, by allotting points for each selected parameter.\r\nAccording to the recommended criteria, the cases were divided into active (n=26) and inactive forms (n=25). There were no significant statistical differences regarding CAS\r\nbetween euthyroid cases (n=14) and dysthyroid cases (n=37). Serum thyroid receptor antibodies (TRAb) levels did not correlate with CAS or severity scores. Severity scores\r\ncorrelated significantly with CAS (Pearson correlation index 0.546, r2=0.290, p=0.0001).\r\nConclusion. Active forms of GO showed higher severity scores than the inactive ones. The severity scores correlated significantly with CAS scores. Neither CAS, nor severity scores correlated significantly with the severity of thyrotoxicosis.

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.

Background. The COVID-19 pandemic hit the world in late 2019, and by 2020, everyone was affected. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) belongs to the beta-coronavirus genre and uses the angiotensin-converting enzyme 2 (ACE2) receptor to penetrate cells. Thyroid cells are rich in such receptors. Therefore, this gland is frequently involved alongside other organs in the COVID-19 disease. Aim. To describe COVID-19 inflammation and, eventually, dysregulations of normal thyroid function in a case series of patients diagnosed in a tertiary endocrinology care centre. Patients and Methods. We described subacute thyroiditis cases related to COVID-19 infection or vaccination against SARS-CoV2 infection (clinical manifestations and evolution). We also reviewed the literature data regarding COVID-19 infection or vaccination implications in thyroid pathology. Results. The literature describes two types of thyroid involvement in SARS-CoV2 infection or vaccination: subacute thyroiditis (SAT) and non-thyroidal illness syndrome (NTIS). In our case series, 5 patients (3 males), aged 41-54 years, developed the classical clinical manifestation of SAT related to COVID-19 infection (3 patients, concomitantly to upper respiratory infection or a few weeks apart) or anti-SARS-CoV2 ARNm vaccination (1-2 weeks after the vaccine administration). Clinical, laboratory and imaging findings and the evolution (steroid anti-inflammatory treatment used in 4/5 cases) were unremarkable compared to other SAT etiologies. Conclusion. We found no differences between the ”typical” viral and post-COVID-19 SAT regarding clinical presentation, severity, response to treatment, and thyroid function alteration. The only remarkable difference is the association of SAT with anti-SARS-CoV2 ARNm vaccination

Objective. Unilateral adrenalectomy (UA) is an alternative for treatment in bilateral adrenal incidentaloma (AI) to avoid possible long-term risks of bilateral adrenalectomy. In this study, we aimed to evaluate the effectiveness of UA in bilateral AI patients with subclinical hypercortisolemia (SH). Method. A total of 35 patients were included in this study. The patients were divided into two groups; those who underwent UA (n=27) and patients without adrenalectomy (PWA) (n=8). Hormone tests related to cortisol mechanism were reviewed to analyze results at the time of diagnosis compared to the latest available results to figure out any changes in cortisol mechanism and determine whether SH has recovered or not. Results. Median age of PWA group were higher compared to UA group (p=0.03). Median duration of followup in groups were similar (p=0.3). In the PWA group, none of the patients recovered from hypercortisolemia during their follow-up. In UA group 92.6% of the patients went into remission, whereas during follow-up 3.3% had recurred and another 3.3% were found to have post-adrenalectomy persistent SH. Patients in UA group had lower final cortisol level following dexamethasone suppression (p=0.003) and higher final adrenocorticotrophic hormone (ACTH) levels (p=0.001) than patients in PWA group. In UA group, final basal cortisol level (p=0.009) and final cortisol level after 1 mg dexamethasone suppression test (DST) (p=0.004) were lower than corresponding levels at the time of diagnosis. Discussion. Our study demonstrates unilateral adrenalectomy targeting the side with the larger lesion is an effective approach to reduce excess cortisol levels in bilateral AI patients with SH.

Context. Different vitamin D analogs might have advantages over calcitriol. Objective. To evaluate the effects of paricalcitol vs. calcitriol based vitamin D receptor activators on calcium-phosphate metabolism and pulse wave velocity in hemodialysis patients. Design. Observational, cross-sectional and 1 year follow-up study. Subjects and Methods. 181 hemodialysis patients were enrolled in this study as divided in to 5 groups based on vitamin D therapy. Baseline and 12th month data on blood biochemistry, pulse wave velocity and cumulative dose of treatments were compared in each study group as well as in overall paricalcitol vs. calcitriol-based treatment groups. Results. From baseline to 12th month, significant improvement in pulse wave velocity and parathyroid hormone was shown in paricalcitol-based treatment group without a significant change in calcium, phosphate, alkaline phosphatase. A significant increase in pulse wave velocity, serum phosphate levels, calcium x phosphate product and serum alkaline phosphatase levels were noted in calcitriolbased treatment group with no significant change in serum calcium and parathyroid hormone levels. Conclusion. Our findings revealed superiority of paricalcitol than calcitriol based vitamin D receptor activator therapy in terms of serum phosphate levels, CaxP product, dose requirement for vitamin D and the control of pulse wave velocity.

Context. Impaired flow mediated dilatation (FMD) and increased carotid intima media thickness (CIMT) are the antecedent forms of atherosclerosis. Objective. The aim of this study was to evaluate vascular structural and functional changes in patients with asymptomatic primary hyperparathyroidism (APHPT), and whether biochemical alterations, related with PHPT and oxidative stress marker serum advanced oxidation protein products (AOPPs), may have influence on vascular alterations. Design. This is a cross sectional clinical study. Subject and Methods: Thirty-four patients with APHPT and 29 sex- and age and cardiovascular risk factors matched control cases were included in this study. Endothelial function was evaluated by FMD of the brachial artery; CIMT was measured by ultrasonography; in addition serum AOPPs and biochemical parameters were determined. Results. Serum Ca levels were higher in the patient group [10.93±0.60mg/dL vs. 9.45±0.31; p<0.001]. FMD measurement was significantly lower in patients group [0.07 (0.01-0.26) % vs. 0.14 (0.04-0.22) %; p=0.01]. CIMT measurements were comparable between the groups [52 (35- 69) mm vs. 56 (38-70) mm; p=0.821]. AOPPs levels were significantly higher in the patients [136.43 (55.14-1352) mmol/L vs. 84 (53.18-595.48) mmol/L; p=0.026]. There were significant negative correlations between FMD and serum Ca (r=–0.339, p<0.001); and serum AOPPs levels (r=–0.275, p<0.005). Serum Ca (p=0.007, β=–0.353) and AOPPs (p=0.024, β=–0.243) levels and hyperlipidemia (p=0.024, β=–0.288) were the predictors of FMD. Conclusions. Vascular endothelial function is impaired in patients with APHPT. Hypercalcemia, increased oxidative stress and hyperlipidemia may have role in the pathogenesis of endothelial dysfunction in patients with APHPT.

Context. Accumulating data supports the key role of disrupted amino acids (AAs) metabolism in diabetes. Conflicting data regarding the relevance of serum AAs in diabetes and hypertension suggest that their relationship needs further investigation. Objective. To investigate serum AAs as biomarkers of increased BP variability evaluated during 24-hour ambulatory BP monitoring in the presence of type 2 diabetes. Design. Cross-sectional. Subjects and Methods. We analyzed serum AAs using targeted metabolomics (ultrahigh-performance liquid chromatography/mass spectrometry) in patients with type 2 diabetes (n=80). BP variability was assessed using 24-hour ambulatory BP monitoring. Participants were divided into two groups based on the 24-hour diastolic BP variability median value. Results. Aspartic acid, isoleucine, leucine, and phenylalanine were significantly lower, while glutamine was significantly higher in the group with higher diastolic BP variability (p-value <0.05 and variable importance in the projection >1). Corresponding pathways identified as disrupted in patients with diabetes and a higher 24-hour diastolic BP variability were phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and alanine, aspartate, and glutamate metabolism (pathway impact value >0). Conclusions. We identified specific changes in serum AAs and target AAs pathways in relation to increased 24-hour diastolic BP variability in patients with type 2 diabetes.

Background. Antineutrophil cytoplasmic antibodies (ANCA) positivity is usually determined in vasculitis of medium and large arteries. In literature, data related to the prevalence of ANCA positivity and the development of antibodies after antithyroid therapy in Graves’ disease are quite rare. Aim. To investigate the titers of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in Graves’ patients treated with propylthiouracil (PTU) and to determine the factors that may contribute to ANCA positivity. Subjects and Methods. Fifty-two Graves’ patients treated with propylthiouracil (PTU) were included into the study. The control group consisted of 37 healthy subjects. MPO-ANCA and PR3-ANCA titers were measured in both groups. Results. Mean titer of PR3-ANCA in Graves’ group was significantly higher than in controls (p=0.025), but no significant difference was found in the titer of MPOANCA between two groups (p=0.060). A positive correlation was observed between PR3-ANCA titer, and anti-thyroid peroxidase antibody and anti-thyroglobulin antibody levels in Graves’ patients (p=0.001, r=0.447 and p=0.030, r=0.310, respectively). PR3-ANCA titer in anti-thyroglobulin antibody positive patients was higher than those with negative antibody (p=0.018). A positive correlation was detected between the duration of treatment and PR3-ANCA titer (p=0.024, r=0.314). Both MPO-ANCA and PR3-ANCA were positive in two Graves’ patients, while only MPO-ANCA was positive in two patients. No signs of vasculitis in ANCA positive patients were observed. Conclusion. Propylthiouracil (PTU) may cause ANCA positivity, but no vasculitis may develop in most of the cases. A correlation was determined between PR3- ANCA titer, and thyroid autoantibodies and the duration of treatment.