ACTA ENDOCRINOLOGICA (BUC)

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.

Context. Thyroid incidentaloma is a common disorder in endocrinology practice. Current literature regarding the risk of thyroid cancer in incidentalomas found in patients with non-thyroid cancer is limited. Objective. The aim of the present study was to investigate the frequency of thyroid malignancy in thyroid incidentalomas detected in patients with non-thyroid cancer. Design. Case control study. Subjects and Methods. The database of 287 thyroid nodules from 161 patients with a history of nonthyroid cancer followed between 2008 and 2014 were retrospectively evaluated. Results. From 287 thyroid nodules, 69.7 % had a benign final cytology. Thyroid cancer detected in one nodule while follicular neoplasia detected in 4 nodules, atypia of unknown significance (AUS) detected in 10 nodules, Hurthle cell neoplasia detected in 5 nodules and suspicious for malignancy detected in 6 nodules according to fine needle aspiration biopsy results. Metastasis of the non-thyroid cancer to the thyroid gland was detected in 4 nodules. Twenty seven nodules from 15 patients were removed with surgery. There were 3 malignant nodules found after surgery (1 papillary, 1 follicular and 1 medullary cancer). In addition to these three thyroid cancers, two patients with benign nodules had co-incidental thyroid cancer detected after surgery. Finally, 11.1 % of thyroid nodules which underwent thyroid surgery had malignant histopathology except for co-incidental and metastatic cancers. Conclusions. The frequency of thyroid malignancy seems not to be substantially increased in incidental thyroid nodules detected in patients with non-thyroid cancer when these patients were evaluated in nodule-based approach.

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.

Objective. Few prognostic analyses have been conducted for papillary thyroid cancer (PTC) patients with preablative stimulated Tg >10 ng/mL. We investigated the therapeutic responses and prognosis of these patients after the initial radioiodine (RAI) therapy. Methods. We retrospectively assessed 256 patients with PTC who underwent RAI remnant ablation after total thyroidectomy, and all presTg levels were >10 ng/mL. We assessed therapeutic responses and influencing factors 6–12 months after the initial RAI therapy. The Kaplan-Meier method was used to analyze progression-free survival (PFS). Results. After initial RAI therapy, excellent (ER), indeterminate (IDR), biochemically incomplete (BIR), and structurally incomplete (SIR) responses were identified in 5.1% (13/256), 22.6% (58/256), 46.9% (120/256), and 25.4% (65/256) of the patients, respectively. Among them, incomplete response (IR [BIR+SIR]), accounting for 72.3% of the responses. Univariate and multivariate analyses showed that presTg (OR=1.047, 95% CI 1.027– 1.066, p=0.000), sex (OR=3.356, 95% CI 1.613–6.986, p=0.001), and tumor size (OR=1.431, 95% CI 1.050–1.951, p=0.023) were independent risk factors for IR. ROC analysis identified presTg levels and tumor size cutoffs of 24.4 mg/ mL and 2.3 cm, respectively, for predicting IR. The PFS was significantly shorter in the SIR group than in the ER, IDR, and BIR groups (p=0.020). At the last follow-up, the number of patients with SIR decreased significantly (65 to 44 cases). Conclusions. PresTg level, tumor size, and male sex were predictive of IR, and patients with initial SIR showed the poorest prognosis. Individualized interventions can improve the prognosis of patients with an initial SIR.

Introduction. Non-diagnostic (ND) fine needle aspiration biopsy (FNAB) results are problematic for clinicians who want to accurately diagnose malignancy and avoid unnecessary thyroidectomies. In this study, we aimed to investigate the incidence of malignancy in nodules whose first FNAB result was ND, and ultrasonography (USG) findings affecting malignancy and the effectiveness of repetitive biopsies. Patients and Method. In our clinic, 156 consecutive nodules whose first FNAB were ND according to the Bethesda system and underwent thyroidectomy between 1 January 2011 and 1 January 2018, directly or after repeated biopsies, were retrospectively analyzed. Results. Malignancy was detected in 44 (28%) of 156 nodules that were ND in the first FNAB. Twenty-two (31%) of 72 nodules that underwent FNAB for the second time resulted in ND again. The malignancy rate of nodules with two consecutive ND results was 23%. Of the USG features, a significant correlation was found between malignancy and solid nodule structure (p<0.001), microcalcification (p=0.025), cervical lymphadenopathy (LAP) (p=0.004) and medium-high risk USG pattern (p=0.002). In multivariate analysis, only the solid nodule structure (p<0.002) and the presence of cervical LAP (p=0.013) resulted as independent predictive factors. Conclusion. Diagnostic thyroidectomy is an effective method for reaching the diagnosis in selected patients considering the USG findings.

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.

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.

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.

Context. Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. Objective. We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. Design. Cross-sectional, observational study. Subjects and Methods. 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. Results. Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. Conclusions. Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Cinacalcet is used to treat tertiary hyperparathyroidism in renal failure. However, its use in pregnancy and hereditary hypophosphatemic vitamin D resistant rickets (HVDRR) has not been reported. In this study we describe the use of cinacalcet in a case of HVDRR with tertiary hyperparathyroidism diagnosed during pregnancy, in a tertiary care hospital in an academic center. A 29 year old woman with HVDRR was found to have tertiary hyperparathyroidism at week 15 of her second pregnancy: serum calcium 11.4 mg/dL, intact parathyroid hormone 307 pg/mL. Reductions in potassium phosphate and calcitriol were unsuccessful in restoring normocalcemia. Cinacalcet was started to avoid parathyroidectomy and to reduce the risk of hypercalcemia to the mother and fetus. After 10 weeks of treatment, calcium normalized but placental abruption prompted delivery at week 27 of gestation. A healthy live male was born with weight of 964 g and serum calcium of 9.0 mg/dL. After delivery cinacalcet was stopped. Eight months later, calcium was 10.0 mg/dL and intact parathyroid hormone 426 pg/mL. This case demonstrates the successful use of cinacalcet during pregnancy to manage hypercalcemia in a patient with HVDRR and treatment related tertiary hyperparathyroidism.