ACTA ENDOCRINOLOGICA (BUC)

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. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Context. Anti-Mullerian hormone (AMH) assay is becoming the best indicator of successful IVF treatment response to fertility drugs and could be a useful marker of embryo implantation potential. Various protocols are being used for controlled ovarian stimulation (COS), but there is an uncertainty regarding the implementation of the best protocol for endometriosis patients and also little evidence is available concerning the clinical value of AMH levels in endometriosis. Objective. This study aimed to evaluate the prognostic value of serum AMH levels for pregnancy in COS using GnRH-agonist(GnRH-a) and GnRHantagonist( GnRH-ant) protocols in endometriosis patients. Design. This is a cross-sectional study between March 2012 and November 2015. Subjects and Methods. Data were collected from 249 COS cycles of endometriosis patients, including 129 cycles with GnRH-a and 120 cycles with GnRH-ant. Patients in each group were classified into three subgroups based on their serum AMH levels. The outcomes of ICSI program were evaluated. Results. The ROC curve analysis showed that embryo and oocyte counts and AMH were equally predictive for pregnancy, as demonstrated by a similar area under the curve (AUC) of 0.69, 0.66 and 0.64, respectively. The sensitivity and specificity for prediction of positive pregnancy were 70.91% and 67.01% for embryo counts, 70.91% and 67.53% for oocyte counts at the cutoff values of 5 and 7, respectively, and 83.64% and 52.58% for AMH levels at the cutoff values of 1.3ng/mL. Conclusions. This study demonstrates that AMH as a single test has substantial accuracy in the prediction of pregnancy using the GnRH antagonist protocol for patients with endometriosis. In other words, AMH assay prior to ovarian stimulation initiation guides the clinicians to choose the antagonist stimulation protocol for the patients with two extreme AMH levels. AMH levels can be used to individualize control ovarian stimulation in endometriosis patients.

abdominal cystic lesions should include investigation of cystic pheochromocytomas. To date only a few cases of purely cystic pheochromocytoma have been reported in the English literature. Aim. To present the management in four cases of silent pheochromocytomas patients who presented with pure or partially cystic abdominal lesions with benign (n:3) and malignant characteristics (nonspecific neuroendocrine tumor) (n:1) in histological evaluation. Results. Resection of the tumor is considered the primary treatment option in the management of pheochromocytoma, and preoperative preparation with alpha and beta antagonists is crucial in order to avoid precipitation of hypertensive crisis during surgical procedures. The absence of clinical symptoms and lack of typical radiological features may complicate the diagnosis of pheochromocytoma resulting with increased mortality and morbidity during surgery. Conclusion. Asymptomatic pheochromocytomas are rare and they are responsible for approximately 5% of adrenal incidentalomas. These lesions may be referred to surgery as clinically nonfunctional adrenal adenomas.

We present the case of severe hypocalcaemia in a 5 weeks old baby, secondary to pre and postnatal vitamin D deficiency. The symptomatic hypocalcaemia led to several life threatening episodes of seizures. Following initial calcium gluconate infusion, multiple phospho-calcic deposits in the soft tissue and cerebral tissue were observed. A multifactorial etiology of calcinosis cutis was suggested by the association between infusion of high and repeated doses of calcium gluconate in a severely hypocalcaemic baby, with a low 25- hydroxyvitamin D3 level, associated to a renal and bone relative resistance to the high level of PTH. The aim of this report is to raise pediatric health care professionals awareness on the relatively rare entity known as calcinosis cutis.

Context. Adiponectin is an abundant adipokine, which has antiinflammatory, anti-atherosclerotic and vasoprotective actions, and potential antiresorptive effects on bone metabolism. It seems to be directly involved in the improvement and control of energy homeostasis, protecting bone health and predicting osteoporotic fracture risk. Objective. To examine the relationship between adiponectin level and bone mineral density (BMD) in postmenopausal women with metabolic syndrome (MetS) and low BMD, and to estimate the prognostic significance of adiponectin in osteoporosis. Design. Clinical-laboratory cross-sectional study including 120 middle-aged and elder women (average 69.18±7.56 years). Subjects and Methods. The anthropometric parameters were measured for all examinees. Lumbar spine and hip BMD, as well as body fat percentage, were measured using a Hologic DEXA scanner. In all subjects serum adiponectin concentration was measured by ELISA method. Results. The level of adiponectin was significantly positively correlated with BMD-total, BMD of the lumbar spine and BMD of the femoral neck (r=0.618, r=0.521, r=0.567; p<0.01). Levels of adiponectin and BMD are significantly lower in post-menopausal women with MetS and osteoporosis compared to patients with osteopenia (856.87±453.43 vs. 1287.32±405.21 pg/mL, p<0.01; BMD, p<0.05), and the highest values in healthy examinees. A cutoff value of adiponectin level for osteoporosis/osteopenia was 1076.22/1392.74 pg/mL. Conclusions. Post-menopausal women with MetS have significantly lower adiponectin level and low BMD compared to healthy examinees. Adiponectin may be an early, significant and independent predictor of developing osteoporosis in women with MetS, especially in postmenopausal period.

Introduction. Our aim was to compare the effects of conventional diabetic diet with refined carbohydrate restricted diet on glycemic and metabolic parameters in type 2 diabetic patients who were treated by insulin.\r\nMaterials and methods. A hundred type 2 diabetic patients treated by insulin, randomized into two groups. The first group (n:50) was given a low refined carbohydrate\r\ndiet , the second group was given conventional diabetic diet. Metabolic parameters were evaluated at the beginning and at the end of the 3rd month of randomization.\r\nResults. There were no statistically significant weight change differences between groups (p=0,237). Changes in the HbA1C level (&#916; HbA1C) in the basal insulin-refined\r\ncarbohydrate restricted diet group, in the basal insulin-conventional diet group and in the premixed insulin-conventional diet group were -1.22% (p<0.001), -0.51% (p=0.13) and -0.66%(p=0.155), respectively. Symptomatic hypoglycemic episodes were reported only by the\r\npatients in premixed insulin group.\r\nConclusion. A diet rich in nutrients with sole exclusion of refined carbohydrates has been shown to be as effective as a stricter conventional diet and therefore it has to be\r\nconsidered as a preferable treatment option.

Objective. To compare two chromatographic methodologies for determination of plasma phenylalanine (Phe) and their usefulness for diagnosing hyperphenylalaninemia (HPA) and phenylketonuria (PKU). Methods. The plasma amino acids were isolated and concentrated from blood collected from infants with HPA detected by newborn screening. The plasma Phe was determined in parallel by HPLC and by image-densitometry of 2D-TLC plates. Results. Typical examples of 2D-TLC plates and HPLC chromatograms from infants with HPA and PKU are presented and evaluated. The Phe spot was visible on 2D - TLC plates at Phe concentrations higher than 300 μmol/L. The standard calibration curve traced after imagedensitometry of the Phe spot presented high dispersion of values at each concentration of Phe, high SD values, the equation of the curve having a low R-squared value (0.862). In contrast, the standard calibration curve obtained by HPLC shows linearity on the range of concentrations from 100 - 16,000 μmol/L, extremely small SD values, the equation of the curve has a very high R-squared value (0.999). Conclusions. The HPLC methodology is appropriate to confirm HPA detected by newborn or selective screening of PKU. The 2D - TLC methodology is adequate to detect patients with severe PKU.

Context. Post-operative clinical and biochemical hypocalcemia is a common complication of thyroid surgery and the correlation with incidental parathyroidectomy (IP) remains controversial. Objective. To evaluate the incidence of IP during TT, its correlation to early post-surgery hypocalcemia, and its potential risk factors. Patients and Methods. 77 consecutive patients submitted to thyroid surgery between January 2018 and December 2019. Demographic, clinical, biochemical, surgical and histopathological factors were assessed. Statistical multivariate analysis was performed to identify the risk of IP. Results. IP was evident in 22 (28.5%) patients who underwent TT, TT with lymph node dissection of the central compartment (CLND) and reoperation for previous hemithyroidectomy with CLND. Early symptomatic hypocalcemia 24 hours after TT was demonstrated in 12/22 (54.5%) patients, with PTH value of <14pg/mL in 7/12 (58.3%) patients, and in 6 of these 7 patients (85.7%) the PTH value was <6.3pg/mL. In 5/22 (22.7%) patients the IP was associated with biochemical hypocalcemia <8.4mg/dL, and in 5/22 (22.7%) patients anatomical damage was not associated with a reduction in plasma calcium levels. The severity of early post-op hypocalcemia was not correlated with the number of parathyroid glands left in situ. The multivariate analysis did not show statistically significant values between the clinical-pathological variables and increased risk of IP. Conclusions. No IP clinical-pathological risk factors have been identified during thyroid surgery. In all cases of TT, with or without CLND, the meticulous identification of the parathyroid glands, whose incidental removal is frequently associated with clinical and biochemical hypocalcemia, is recommended.

Context. Incidentally discovered solid adrenal tumors must be evaluated from two points of view: the risk of malignancy and the secretory feature. Objective. Our aim was to evaluate the surgical technique option in relation with clinical and histopathologic features. Design. We performed a retrospective study that included patients with adrenal gland tumors. Subjects and methods. All patients were operated between 2012 and 2019 by the same surgical team in a single center. Results. The batch included 102 patients with adrenal tumors operated through open surgery (OS, n=41) and laparoscopic surgery (LS, n=61). Tumor localization was especially on the right adrenal gland (n=52, 50.98%). Primary origin of the adrenal gland tumors was in 82 cases (80.39%) and a metastatic origin in 16 cases. Average dimension for surgical resected tumors was 4.02 cm (0.9-12 cm) for the LS group as compared to 7.22 cm (1.3-19 cm) for OS group with a predominant type of surgery represented by adrenalectomy and a conversion rate of 2.94%. The hospital stay was 7.22 days (5-12 days) in the LS group versus 12.72 days (6-57 days) in OS group with significant differences (p<0.01). Also, the postoperative recovery was significantly different (6.5 days versus 2.62 days, p<0.01). Conclusion. Laparoscopic approach represents the gold standard in adrenal gland tumors less than five centimeters in size. Adrenalectomy is mostly performed by LS and adenoma is the most frequent histopathologic type, while pheochromocytoma is operated through OS. LS has a significantly reduced hospitalization and postoperative stay compared to OS.