ACTA ENDOCRINOLOGICA (BUC)

Context. In patients with suspected primary aldosteronism (PA), the aldosteroneto- renin ratio (ARR) is the most frequently recommended screening test. Further evaluation is based on hormonal changes during volume expansion. Both analyses are critically dependent on an accurate estimation\r\nof renin concentration. Direct active renin (DAR) is a novel laboratory technique used for plasma renin assessment.\r\nObjective. The objective of this study was to evaluate DAR for use in PA diagnostic work-ups.\r\nSubjects and Methods. The study enrolled 69 healthy volunteers. Blood sampling was conducted before and after an\r\nincrease in oral salt intake. Furthermore, a subset of 32 individuals underwent a saline infusion suppression test. DAR and serum aldosterone were measured in all blood samples. To calculate the ARR, serum aldosterone and DAR were expressed in ng/L.\r\nResults. ARR values [median (range); 97.5 percentile] associated with normal and elevated oral salt intake were 8.4 (0.6-37.7); 26.3, and 6.8 (1.1-37.7); 19.6, respectively. DAR and serum aldosterone concentrations\r\n[median (range); 97.5 percentile] after saline infusion suppression were 2.9 (2.7-10.7); 7.2 ng/L and 30 (30-72); 54 pmol/L, respectively.\r\nConclusions. The observed values may be useful in excluding a diagnosis of PA.

Background. Ectopic thymus could be located intrathyroidal, therefore fine ultrasound details are useful for this differentiation. Aim. To investigate differences in stiffness and vascularity properties among thyroid nodules and intrathyroidal ectopic thymus (IET) by obtaining quantitative data in children. Patients and Methods. Twenty-seven thyroid nodules and 20 IET in children were evaluated in terms of vascularity index (VI) via superb microvascular imaging (SMI) and stiffness by shear wave elastography (SWE). Differences in the volume, VI, and SWE parameters of the lesions were assessed by using the Mann-Whitney U test. Association of the age, lesion volume, SWE, and VI parameters was investigated by using Spearman’s correlation analysis. The optimal cut-off values for stiffness and vascularity in the differentiation of nodules from IET were calculated with ROC analysis. Results. The median (range) age of the participants with thyroid nodules and IET were 15.6 (10-18) years and 8.8 (3-14) years, respectively. The medians (range) VI of the IET and thyroid nodules were 4.7 (0.2-16) % and 23.8 (7.5-40)%, respectively. The median SWE values were 7.6 (4.4-9.5) kPa and 15.58 (8.5-23.4) kPa for IET and nodules, respectively. There have been highly significant differences among medians of volume, SWE, and VI values of the lesions. Significant positive correlations were found between VI and SWE parameters (p=0.001, r=0.64), and volume with VI (p=0.018, r=0.34) and SWE (p:0.001, r= 0.5). The diagnostic accuracies were 93%, 91% with the cut-off values as 9.2 kPa, 13% for the SWE and SMI, respectively. IETs were found to be less vascular and less stiff than thyroid nodules. Conclusions. IETs could be easily and confidently differentiated from nodules using SWE and SMI quantifications. This discrimination prompts the reduction of unnecessary interventional procedures.

In acromegalic patients growth hormone (GH) excess induces insulin resistance (IR) but whether this is sufficient for pre-diabetes to occur is a matter of debate.\r\nAim. To assess the relative role of IR and insulin secretion in the pre-diabetes of acromegaly.\r\nMethods. 126 patients with acromegaly (79 women, 47 men) were included. Plasma glucose, GH and insulin levels were measured basal and 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT). Basal and stimulated IR was assessed by homeostasis model assessment (HOMA), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI) derived from OGTT (OGTTISI) respectively. Basal and stimulated insulin secretion was assessed using HOMA-B% index and insulinogenic index (IGI), respectively. The local Ethic Committee approved the study.\r\nResults. There were 51 subjects with pre-diabetes and 75 subjects with normal glucose tolerance (NGT). Pre-diabetes group had a significantly higher HOMA-IR index (4.8?3.3 vs 2.5?1.6, p<0.001) and nadir GH in OGTT (9.4 (4.3, 22.2) vs. 4.8 (2.2, 14.5) ng/mL, p=0.02) than NGT group. HOMA-IR did not correlate with nadir GH serum level in pre-diabetes group (r =0.22, p=0.12) but correlated significantly in NGT group (r= 0.5, p<0.001). In contrast, the pre-diabetes group had a lower HOMA-B% index than NGT group (165.4?15.7 vs 228.5?29, p<0.001). HOMA-B% did not correlate with nadir GH in both groups. Unadjusted IGI did not differ between the two groups (0.40?0.07 vs. 0.48?0.05, p=0.34) but became statistically significant after adjusting for both basal IR (HOMA-IR) (0.31?0.06 vs. 0.54?0.05, p=0.01) and stimulated IR (OGTTISI) (0.30?0.06 vs. 0.54?0.05, p=0.005). There were no significant differences between pre-diabetes and NGT groups regarding age, duration of acromegaly and sex.\r\nConclusions. Our data suggest that reduced basal and stimulated insulin secretion express the failure of &#946;-cells adaptation to increased GH-induced-insulin resistance and is the pathogenic mechanism of pre-diabetes in acromegaly.

Content. Metabolically healthy obese (MHO) individuals are characterized by absence of metabolic syndrome. The role of autonomic nervous system in metabolic profile of obese subjects has not been sufficiently investigated. Objective. We analyzed heart rate variability (HRV) in MHO and metabolically unhealthy obese (MUO) premenopausal women. Design. In 42 women metabolic profile was defined as MHO and MUO. Subjects and Methods. For metabolic profile Wildman, IDF and HOMA-IR criteria were used. Autonomic nervous system activity was assessed by analysis of heart rate variability. Results. There was no significant difference in HRV between MHO and MUO premenopausal women. In Wildman division, after adjustment for systolic blood pressure, RRNN and LF/HF were statistically different between groups (p=0.0001; p=0.029). In IDF division, adjusting for waist circumference, LF was significantly different between groups (p=0.004). In HOMA division, adjusting for HOMA, groups were different in SDNN (p=0.009), RMSSD (p=0.002), pNN50 (p=0.003), HF(p=0.002) and TP (p=0.005). Conclusions. Autonomic nervous system does not share the leading role in premenopausal women metabolic profile. The differences in HRV between MHO and MUO women depend on the metabolic health criteria. Systolic blood pressure, HOMA and waist circumference have significant effect on HRV differences between MHO and MUO premenopausal women.

Objective. Metabolic syndrome (MetS) is a metabolic condition with high prevalence worldwide. This study aims to examine the relationship between serum concentrations of gastrointestinal hormones such as cholecystokinin (CCK), ghrelin, peptide YY (PYY), and high sensitive C-reactive protein (hs-CRP) and the ingredients of MetS in obese population. Subjects and Methods. This case-control study included 40 obese subjects (20 with MetS and 20 BMI and age-matched control individuals). The age range of the participants was 20-50 years and the participants’ anthropometric characteristics were measured. Serum lipids and the concentrations of oxidized low density lipoprotein (Ox-LDL), insulin, hs-CRP, CCK, PYY, and ghrelin were assessed with commercial ELISA kits. Results. Serum levels of hs-CRP, total cholesterol (TC) and triglycerides (TG) in patients with MetS were significantly higher while CCK and insulin concentrations were higher in obese non- MetS group (P <0.05). PYY had a negative association with waist circumference (WC) and high density lipoprotein cholesterol (HDL-C) and ghrelin had a positive association with systolic blood pressure (SBP) and TC in obese control group (P < 0.05). In obese patients with MetS, hs-CRP had a strong positive association with TG. Conclusion. The current study revealed the possible role of hs-CRP and several GI- hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.

Aim. To evaluate the expression of Galectin-3, Fibronectin-1, Cytokeratin-19 and HBME1 in benign and malignant thyroid nodules and to assess their diagnostic value. Methods. Immunohistochemical analysis was performed on 59 surgically removed thyroid nodules, including 34 carcinomas (12 papillary, 2 tall cell variants, 3 lymph node metastases from papillary carcinoma, 5 follicular variants of papillary carcinoma (FVPTC), 3 anaplastic, 5 follicular and 4 Hürthle cell carcinomas), as well as 25 benign lesions (10 follicular adenomas, 4 Hürthle cell adenomas, 11 nodular goiters with surrounding normal thyroid tissue).3 expression in all malignant lesions except for one case of FVPTC and one follicular carcinoma. Normal thyrocytes and the majority of the benign lesions were negative for all markers. Statistical analysis of each protein confirmed that Galectin-3 was the most sensitive (94%), followed by Cytokeratin-19 (88%). Fibronectin-1 and HBME1 proved to be less sensitive (56% and 68%, respectively), but more specific (92% specificity for each of them). Coexpression of two or more proteins was restricted to carcinomas, while their concurrent absence was highly specific for benign lesions. Comparing the immunopositivity in follicular carcinoma versus adenoma we achieved 80% sensitivity for Galectin-3 and 100% specificity for HBME1. For distinguishing the Hürthle cell lesions, Fibronectin-1 turned out to be more sensitive than Galectin-3 and Cytokeratin- 19. Conclusion. Our findings suggest that immunohistochemical panel consisting of Galectin-3, Cytokeratin-19, HBME1 and Fibronectin-1 might contribute to differential diagnosis between malignant and benign thyroid nodules, including those with follicular architecture.

Introduction. With the introduction of iodized salt, more and more people are exposed to iodine sufficiency in some regions. The purpose of this study was to investigate the prevalence of nontoxic nodular goiter (NTNG) in the littoral region with high iodine supply after a nearly twodecade universal salt iodization. Subjects and Methods. Eight hundred and thirtyfive participants (from 25~65 years; males 421 and females 414) were invited for the study from Huan-cui District of Weihai City, Shandong Province from January 2013 to September 2014. All participants were inspected and diagnosed by endocrinologists according to the thyroid function tests and the thyroid gland imaging. After the normal diet of three days, the urine samples of the participants were collected between 8:00AM and 9:00AM and the urinary iodine (UI) concentrations were analyzed using Urinary Iodide Test Kit. Results. The overall prevalence of NTNG in the region was 40.1%, and different prevalence occurred in the different age ranges (p<0.01). The prevalence of NTNG was 32.51%, 37.44%, 49.70%, 58.57 and 74.77% in the age group of ≤ 30, 31-40, 41-50, 51-60 and >60 years, respectively. Meanwhile, the prevalence of NTNG in women (42.08%) was higher than that in men (34.29%, p<0.05). The median of UI concentrations were 139.4μg/L and 101.5μg/L for the group with NTNG and without NTNG, respectively (p<0.01). However, there was no significant difference in UI concentrations among the groups with different age ranges (p>0.05), and statistical difference was not observed for UI concentrations between women and men (p>0.05). Intriguingly, higher UI concentrations were found in the group with larger thyroid size (p<0.01). Conclusion. The iodine excess can lead to the high occurrence of nodular goiter in the littoral region, and individual UI concentration detection is recommended for the iodine nutritional status analysis among normal people when Universal Salt Iodization (USI) continues to be implemented in the region.

Context. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer due to its high fibrotic content; it can affect the blood flow resistance. Objective. To introduce duplex Doppler ultrasonography (DDUS) parameters of papillary thyroid carcinoma (PTC) and their correlation with size. Design. The study was designed as a prospective study. Subjects and Methods. Thyroid nodules of the patients who were already scheduled for thyroid surgery either for malignant thyroid nodules or multinodular goiter were evaluated for DDUS parameters. Size, systolic to diastolic flow velocity (S/D) ratio, pulsatility index (PI), and resistive index (RI) of each nodule were recorded. Nodules were diagnosed as PTC or benign nodules based on histopathology. DDUS parameters were compared between PTCs versus benign nodules and micro PTCs (≤ 10 mm) versus large PTCs (> 10 mm). A correlation analysis was performed between the size and DDUS parameters. Results. 140 thyroid nodules (30 PTCs, 110 benign nodules) were obtained. The mean S/D ratio, PI, and RI values were significantly higher in PTC than in benign nodules (p values were 0.0001, 0.0003, and 0.0001 respectively). The optimal cut-off values of S/D (0.732), PI (0.732), and RI (0.738) had accuracy rates of 71%, 69%, and 69%, respectively. There was no statistically significant difference between micro PTC and large PTC with regards to DDUS parameters. The size and DDUS parameters of PTC showed no significant correlation. Conclusions. PTC has a high resistive flow pattern regardless of its size; however the clinical utility of DDUS to differentiate a PTC from benign nodule is limited.

Cardiovascular disorders represented by congenital malformations, hypertension, aortic dilatation which can emerge in dissection or rupture and ischemic heart disease are common in Turner syndrome (TS) and life-threatening. Echocardiography and magnetic resonance imaging represent complementary diagnostic methods used to assess cardiovascular status. Unfortunately, normal reference ranges for cardiac and aortic measurements are established only in unselected TS patients, preventing a delineation between patients with and without cardiovascular pathology. We performed echocardiography in 15 patients with TS, aged 12-33 years (mean 21.8 years, standard deviation 6.37 years) without cardiovascular and renal malformations, hypertension or aortic dilatation and 30 normal controls; karyotype was 45,XO in 11 patients and 45,XO/46,XX in four patients. To minimize the influence of body size, ratios of aortic and cardiac chambers dimensions were calculated. As expected, we found smaller dimensions in TS versus controls but only the ascending aorta, left atrium and diastolic left ventricular diameters and the ratio diastolic / systolic left ventricular diameters reached statistical significance. Only aortic dimensions were entirely independent of age, height, weight and BMI with a 95% confidence interval of 14.28 &#8211; 25.32 (mean 19.8) mm for the aorta at the annulus and 95% CI 21.42 &#8211; 29.36 (mean 25.54) mm for the ascending aorta. The ratios ascending aorta/ systolic left ventricular diameter (95% confidence interval 0.54 &#8211; 1.34; mean 0.94), aorta at the annulus/systolic left ventricular diameter (95% CI 0.44 &#8211; 0.92; mean 0.68) and aorta at the annulus/ diastolic left ventricular diameter (95% CI 0.36 &#8211; 0.61; mean 0.49) are independent of age, height, weight and can also be reliable for detection of aortic dilatation.

Aim. The efficacy of various treatment regimens in severe premenstrual syndrome, (PMS), and premenstrual dysphoric disorder, (PMDD).\r\nStudy design. The study group of 92 patients, aged 20-36 years, was assessed for 2 months before and at the end of one of the following 4 months treatment regimens, randomly assigned: A - combined oral contraceptives with drospirenone; B - oral contraceptives without drospirenone; C - selective serotonin reuptake inhibitors; D - EPO and vitamin B6. A not blinded control group of 92 age-matched patients with severe PMS, without medication, was used.\r\nMethods. All 184 patients completed the Prospective Record of the Impact and Severity of Mastodynia (PRISM) calendar published in 1985 (11) for every of the 6 months of the study. We did not manage or analyze PMDD separately from severe PMS. Simple t test of the initial PRISM results was used, as well as Student t test, or the chi2 test / Fisher test for qualitative data for subgroup analysis.\r\nResults. Oral contraceptives with drospirenone (treatment A) significantly improved the breast tenderness (average severity score was 14.5 ? 0.6 before and 8.9 ? 0.7, p< 0.05, after treatment) and the lack of self-control (average severity score was 14.3 ? 0.7 before and 9.1 ? 0.5, p< 0.05 after treatment). However, oral contraceptives without drospirenone (treatment B) also significantly improved the same parameters of PMS: breast tenderness (average severity score was 15.3 ? 0.4 before and 9.2 ? 0.5, p< 0.05 after treatment) and the lack of self-control (average severity score was 15.5 ? 0.5 before and 9.8 ? 0.7, p< 0.05 after treatment). The subgroup on drospirenone oral contraceptives did not show any premenstrual weight gain, unlike the other subgroups. SSRIs (treatment C) significantly improved the lack of self-control (p< 0.01), but without significant effect on breast tenderness and without any effect on the weight gain. EPO and vitamin B6 (treatment D) showed no significant effects.\r\nConclusion. Concerning the number of patients, drospirenone containing oral contraceptives showed effective improvement of PMS in 67.9% (remission) versus 35.9% (remission in the control group without any medication). However, the authors suggest that SSRIs (and not oral contraceptives with or without drospirenone) might be the treatment of choice in cases where mood / behavioral symptoms prevail over physical symptoms.