ACTA ENDOCRINOLOGICA (BUC)

Secondary hyperparathyroidism, i.e. increased synthesis and secretion of parathyroid hormone and gland hyperplasia, is commonly found in chronic kidney disease. Although it is, at first, an adaptive response to the loss of renal functions in order to maintain the calcium/phosphate homeostasis and normal bone turnover, it is also an important cause of increased morbidity in this clinical setting by leading to renal osteodystrophy and cardiovascular complications. Recent advances in the knowledge on the pathogenesis of parathyroid-related complications in renal failure allowed for new therapeutic approaches. However, many problems remain to be solved in the future. This paper briefly presents the current understanding of pathogenic mechanisms of hyperparathyroidism, bone disease and vascular calcification during chronic kidney disease. In addition, it summarizes the main therapeutic methods available today for controlling secondary hyperparathyroidism and the challenges of practitioners concerning this issue. Finally, the current status of secondary hyperparathyroidism management is analyzed, with emphasis on the Romanian experience.

Background. Recent experimental data show that increased plasma adiponectin in chronic kidney disease could be a response to inflammation.\r\nObjective. To identify factors influencing adiponectinemia in patients with type 2 diabetes (T2DM) and microalbuminuria or low grade proteinuria.\r\nDesign. 32 patients with urinary albumin excretion rate (UAER)> 30 mg/g creatinine but without significant proteinuria (< trace COMBUR) were included and compared to 59 normalbuminuric T2DM controls. History, anthropometric measurements, laboratory analysis, total plasma adiponectin were obtained.\r\nResults. In our patients with UAER of 273.51?57.26 mg/g creatinine and estimated glomerular filtration rate (eGFR) 64.92?4.56 mL/min, in simple regression, adiponectinemia\r\ncorrelates inversely to eGFR (p=0.02, r= -0.38), triglyceridemia (p=0.03, r=-0.37) and hemoglobin\r\n(Hb -p= 0.01, r=-0.45) and positively to HDL cholesterol (p=0.001, r=0.54) and UAER (p<0.0001, r=0.71); the two latter parameters remain significant in multiple regression. In controls, adiponectinemia correlates inversely to age (p=0.04, r=-0.26) and BMI (p=0.04, r=-0.24); these and UAER predict adiponectinemia in multiple regression. 11 patients have UAE superior to 300 mg/g creatinine and 21 are strictly microalbuminuric (mean UAER 653.16?97.02 and 83.68?10.28mg albumin/g creatinine respectively). In microalbuminuric patients serum C reactive protein (CRP) correlates positively (p=0.0008, r=0.68) and Hb negatively (p=0.04, r=-0.41) to adiponectinemia; in multiple regression adiponectinemia only depends on CRP. In proteinuric patients CRP and\r\nglycated Hb correlate to adiponectinemia in stepwise multiple regression.\r\nConclusion. Adiponectinemia is mainly predicted by UAER in our cohort whereas it depends on age and BMI in normalbuminuric T2DM controls; in strictly microalbuminuric\r\npatients CRP is a major predictor of adiponectinemia.

Context. Primary hyperparathyroidism (PHPT), characterized by the inappropriate secretion of parathyroid hormone (PTH) with respect to the extracellular calcium concentration. Curative treatment of PHPT is surgery and bilateral neck exploration has been replaced by minimally invasive parathyroidectomy (MIP), with the advanced imaging technologies combined with radio-guided occult lesion localization (ROLL). Objectives. The present study analyzes the MIP data from 45 patients who underwent surgery for parathyroid adenoma and debates if MIP is a feasible technique for the treatment of PHPT. Design. The study presents the MIP excision data of 45 hyperparathyroidism patients with a 58-month follow up period. Results. Forty-five operations were performed for 48 parathyroid adenomas. The mean duration of operation was 22.7 (12-55) minutes. Mean follow-up was 14.2 (6- 26) months. All patients had normal postoperative calcium levels and PTH levels were normal in the follow-up period, except for one persistent hyperparathyroidism. Conclusions. ROLL-guided MIP is a feasible technique for parathyroid surgery and reduces surgeon based failure. It also provides the widespread application of parathyroid surgery by decreasing the need for specific experience.

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.

Objective. Gestational diabetes mellitus (GDM) is defined as glucose intolerance that\r\nis detected for the first time during pregnancy. Normal pregnancy induces insulin resistance\r\nthrough the diabetogenic effects of placental hormones. Glucose tolerance test results in\r\ntwin and singleton pregnancies were compared in this study.\r\nSubjects and Methods. A total of 360 pregnant women were studied. 200 women\r\n(mean age 31.60?2.10 yr) had singleton pregnancies (Group I) and 160 women (mean age\r\n28.20?2.70 yr) had twin pregnancies (Group II). 50- g, 1- hour glucose tolerance test was\r\nconducted on the first prenatal visit. An abnormal glucose screen defined as glucose > 140\r\nmg/dL was followed by a 100g, 3-hour glucose tolerance test. Gestational diabetes was\r\ndefined as the presence of two or more abnormal values during the 3-hour test.\r\nResults. Gestational diabetes was found in 4 of the 200 (2%) singleton pregnant\r\nwomen and 8 of the 160 (5%) twin pregnant women. Group I (Singleton) was further\r\ndivided into two subgroups according to whether the 1-hr plasma glucose level was < 140\r\nmg/dl (Group Ia) or >140 mg/dL (Group Ib). Likewise, Group II pregnancies was also\r\ndivided into two subgoups on the same basis. Mean screening test glucose levels were found\r\nto be 127.8?14.94 mg/dL in Group Ia and 150.8 ? 18.1 mg/dL in Group Ib women. Mean\r\nscreening test glucose levels of Group IIa subjects was 92.80 ? 18.30 mg/dL while that of\r\nGroup IIb subjects was 154.8 ? 27.0 mg/dL. Mean 1st h glucose levels of 100-g glucose\r\ntolerance test was found to be 131.4 ? 32.58 mg/dL in Group I, and 112.5 ? 39.6 mg/dL in\r\nGroup II. Mean 2nd h glucose tolerance test values were 133.2 ? 28.8 mg/dL in Group I and\r\n100.6?28.8 mg/dL in Group II. Mean 3rd h glucose tolerance test values were 107.6 ? 23.58\r\nmg/dl in Group I and 72?16.9 mg/dL in Group II.\r\nConclusion: Glucose screening results and 100-g, 3- hour glucose tolerance test\r\nvalues have been found to be lower in twin pregnancies than in singleton pregnancies.\r\nTherefore, we suggest that these findings be taken into account in developing diagnostic\r\ncriteria for gestational diabetes in twin or more pregnancies.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) plays an important role in the regulation of cellular energy metabolism, and it is involved in obesity and type 2 diabetes mellitus (T2DM). Its expression is elevated in the liver of T2DM mouse models. Literature reports show that chronic β2 stimulation improved insulin sensitivity in T2DM. Objectives. We aimed to test the hypotheses that chronic β2 stimulation-induced improvement in insulin sensitivity involves changes in the expression of PGC-1α and glucose transporter 4 (GLUT4). Animals and Methods. We fed a locally inbred, 8 months old mice, a high fat diet (HFD) to induce diabetes. These mice gained weight and became insulin resistant. The β2 agonist salbutamol had a beneficial effect on both glucose tolerance and insulin sensitivity after 4 weeks. Results. Salbutamol beneficial effect persisted after 4 weeks of its discontinuation. HFD caused an up regulation of the hepatic PGC-1 α expression by 5.23 folds (P< 0.041) and salbutamol reversed this effect and caused a down regulation by 30.3 folds (P< 0.0001). PGC-1 α and GLUT4 expression in the muscle was not affected by salbutamol (P> 0.05). Conclusion. Down regulation of the liver’s PGC- 1 α contributes to the beneficial effect of the chronic β2 stimulation on glucose tolerance and insulin sensitivity in T2DM mice.

Objective. This study aimed to investigate the effect of symptoms of diabetes on the quality of life of individuals with Type 2 diabetes. Method. The study used a cross-sectional design. No sampling procedure was employed in the study; instead, 410 individuals presenting to the Balikesir Atatürk City Hospital Endocrinology and Internal Medicine Polyclinics between December 2016 and July 2017, diagnosed with Type 2 diabetes, and meeting the inclusion criteria were enrolled in the study sample. The study data were collected with a “Socio-demographic Characteristics Questionnaire”, the “Diabetes Symptom Checklist”, and the “SF-36 Quality of Life Questionnaire”. Results. The participants obtained the highest mean scores from the hyperglycemia subscale of the Diabetes Symptoms Checklist (3.35±0.60) and the mental health subscale of the SF-36 Quality of Life Questionnaire (50.65±8.10). The hypoglycemia, cardiology, psychology, and neurology variables included in the model were statistically significant and predicted 35% of the mental subscale score of the SF 36 questionnaire. SF 36 physical subscale score increased as the hypoglycemia, cardiology, psychology, and neurology scores decreased (p<0.05). Conclusion. The participants obtained high scores from the hyperglycemia subscale of the diabetes symptom checklist and mental health subscale of the quality of life questionnaire. Diabetes symptoms were found to affect the quality of life of individuals with diabetes.

Context. Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction. Aim. The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats. Animals and Methods. Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured. Results. The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-α, miR- 126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group. Conclusion. GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels.

Context. Primary hyperparathyroidism (PHPT) is often associated with thyroid disorders like nodular goiter, Hashimoto’s thyroiditis (HT) and Graves’ disease. Objective. Our aim was to explore whether the coexistence with HT affects bone metabolism in patients with PHPT. Design. This was a comparative cross-sectional study carried out in a tertiary inpatient endocrine center from January 2018 through December 2020. Subjects and Methods. A total of 234 patients were diagnosed with PHPT at our endocrine center. One hundred of them were included in the study - 50 with PHPT only and 50 with PHPT and HT. Two control groups were defined: 37 with HT and 37 without PHPT and HT. Serum markers of calcium-phosphate metabolism, bone markers (RANKL, Osteoprotegerin, β-CTX, Osteocalcin) and interleukin-17A were measured. Results. The frequency of HT among patients with PHPT was 37.6% (95% CI 31-43%) and did not differ significantly from that in the general population, 32.5% (95% CI 30-35%). Age, BMI, markers of calciumphosphate metabolism, bone markers and interleukin-17A weren’t significantly different in PHPT with and without HT or between the two control groups. The participants with PHPT had higher levels of interleukin-17A, β-CTX and Osteocalcin (p<0.05) than those without the PHPT. RANKL and Osteoprotegerin in these groups did not differ. Interleukin-17A correlated positively with serum calcium, PTH and RANKL and negatively with serum inorganic phosphate and 25(OH)D. Controlling for HT and age did not change the correlation. Conclusions. In our study, HT has not additional effect on bone metabolism in the patients with PHPT. Higher levels of interleukin-17A in PHPT suggest a possible role in the PTH-induced bone remodeling.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.