ACTA ENDOCRINOLOGICA (BUC)

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.

Background. Fine needle aspiration biopsy (FNAB) is an important tool in the diagnosis of thyroid nodules. Aim. Our aim was to investigate the malignancy criteria in thyroid nodules by gray-scale ultrasonography (US) and duplex Doppler ultrasonography (DDUS), and their usefulness in reducing the number of unnecessary FNAB’s. Study design. This was a prospective observational study. Subjects and methods. 181 benign and 18 malignant thyroid nodules were evaluated by US and DDUS before FNAB or thyroidectomy. US was used to note size, shape, internal structure, nodule echogenicity, marginal properties, peripheral hypoechogenic halo, and microcalcifications. DDUS studies were used to evaluate the maximum and minimum flow velocity (Vmax and Vmin), systolic/diastolic flow velocity ratio (S/D), pulsatility index (PI), resistive index (RI), acceleration time (AT) and acceleration value. Results. Contour irregularity, size and presence of microcalcifications (p<0.001, p=0.02 and p=0.002, respectively) and S/D, Vmin, PI, RI and AT were significantly different (p=0.004, p=0.007, p=0.032, p=0.003 and p=0.003, respectively) were significant for malignant nodules. Benign and malignant nodules with or without suspicious US findings had similar DDUS findings. Vmax, Vmin, PI, RI, and AT were significantly different in the presence of microcalcification (p=0.043, p=0.001, p=0.031, p=0.04, and p=0.019 respectively). AT was significantly different in the case of absence of microcalcification (p=0.019). Comparing the irregular margins, Vmin, PI and RI were significantly different (p=0.014, p=0.003, and p=0.014 respectively). Conclusion. Benign and malignant thyroid nodules can be differentiated using gray-scale US findings and DDUS based indices together to reduce the number of unnecessary FNAB’s.

Background. Small-cell lung carcinoma is a neuroendocrine tumor that exhibits aggressive behavior, rapid growth, early spread to distant sites and frequent association with paraneoplastic syndromes, the most frequent being the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Case report. We present the case of a 66 year-old woman who presented to the Emergency Department for a syncope preceded by vomiting. She had onemonth history of progressive confusion, disorientation, drowsiness, and generalized malaise. At presentation, the biochemical profile showed normal hemogram values, severe hyponatremia (seric sodium level 120 mg/dL), low plasma osmolality (<275 mOsm/ kg). The blood tests for kidney, thyroid and adrenal functions were in normal limits. There was no evidence of congestive heart failure or nephrotic syndrome. A diagnosis of SIADH was made. Because of a high suspicion for lung cancer, chest computed tomography (CT) was done, together with neck, abdominal and pelvic CT scan, all showing normal data, excepting necrotic lymph nodes in the lower right carotid space and right paratracheal. Right laterocervical lymph node biopsy was done. The histopathological and immunohistochemical result showed lymph node metastasis of a neuroendocrine small cell carcinoma, most probably with broncho-pulmonary origin. Conclusion. The case is interesting due to long term absence of any respiratory symptom, absence of identification of pulmonary tumor, despite repeated CT scans, the only clinical manifestations being related to SIADH. Also, it emphasizes the importance of early recognition of SIADH, which may be the only initial manifestation of a neuroendocrine small cell carcinoma.