ACTA ENDOCRINOLOGICA (BUC)

Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Background. The occurrence of mixed dementia defined as the association of Alzheimer’s disease with vascular dementia is increasing due to the global aging of the human population. Since thyroid hormones play a role in cognition and alterations of the thyroid axis occur with aging it is reasonable to assume that thyroid function and cognitive decline in mixed dementia are linked. Objective. To investigate whether there is a link between TSH, oxidative stress, cognitive decline and depression in female patients with mixed dementia. Methods. Fourty female patients with mixed dementia and 10 healthy controls were included in the study. MMSE, depression score (Cornel Scale of depression), TSH, MDA, glutathione were determined. Serum TSH levels correlated with the cognitive decline measured by MMSE (r=0.55 p=0.0002) and with de depression score (r=0.34 p=0.0314). Furthermore an increase in the oxidative stress marker MDA (p=0.0004) and in the antioxidant defense marker Glutathione (p=0.0013) was observed in patients with mixed dementia. In addition the levels of Glutathione correlated with cognitive decline (r=-0.4997 p=0.001) and with the levels of TSH (r=-0.4997 p=0.001). Conclusion. Our results suggest that thyroid function, oxidative stress and mixed dementia are corelated. However, a possible cause and effect relationship is not yet proved.

Background. Chronic inflammation is associated with different cancers, and is identified as a key pathogenic mechanism in ovarian cancer. The purpose of our study was to evaluate systemic inflammation markers, as predictive and prognostic factors, in ovarian cancer patients with initial surgical treatment. Subjects and Methods. We performed a retrospective study on 60 ovarian cancer patients with primary cytoreduction surgery, between 2010-2018, with a follow-up period of at least one year. We analyzed systemic inflammation markers and their correlations with the clinical, paraclinical, tumor characteristics, or treatment particularities, and evaluated them as prognostic factors for overall survival. Results. In the univariate analysis, no statistically significantly differences were observed, by correlating the systemic inflammation markers with age, reproductive status, FIGO stage, or type of cytoreduction. Higher neutrophillymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were statistically significant associated with deceased patients, and lower lymphocyte-monocyte ratio (LMR) had statistical significance for living patients. For the patients in the group, the increase of NLR, as well as of PLR leads to the increased risk of death, and the increase of LMR leads to the decrease of this risk. In the multivariate regression analysis, the increase of NLR determined an increased risk of death by 9.7%, and for LMR a reduced risk of death by 46.9%. Conclusions. Systemic inflammation markers had no statistical significance correlated with age, reproductive status, FIGO stage, serous cancer type, or type of cytoreduction but only with overall survival. NLR is an independent risk factor, while LMR is an independent protection factor as well as optimal cytoreduction.

The aim of this study was to examine the highglucose and high fatty acid status effect on the development of atherosclerosis. Materials and Methods. We used rat thoracic aorta smooth muscle cell line A7r5. We investigated mechanisms underlying high-glucose and high fatty acid (oleic acid) conditions on vascular smooth muscle cell (VSMC) mimicking concurrent status of diabetes and dyslipidemia. Results. Glucose-oleic acid stimulated cell proliferation and migration while the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 were activated. In addition, the expressions of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) enhanced by glucose-oleic acid were increased. The proliferation signal mediated by glucoseoleic acid condition was demonstrated via CTGF/FASN, while MMP-2 was regulated by CTGF but not FASN. Conclusion. Oleic acid in the presence of high glucose level can induce VSMC proliferation and migration leading to diabetes-associated vascular atherosclerosis. Furthermore, via activation of CTGF, increased expression of FASN suggested a possibility of lipogenesis in VSMC which may also contribute to diabetes-associated vascular atherosclerosis.

Introduction. Papillary thyroid microcarcinoma has provoked discussion among the endocrinological community due to the extremely diverse therapeutic methods adopted in international guidelines. From the radical approach of total thyroidectomy with prophylactic central lymphatic dissection to "active monitoring" and opinions such as "papillary microcarcinoma is not carcinoma". Aim. To investigate the factors of invasiveness in papillary microcarcinoma. Material and methods. We included 184 patients with thyroid microcarcinoma, operated in the Department of General Surgery "Kaspela",Plovdiv, for a period of five years. Results. Intra-organ metastases or multifocal growth was identified in 38 of the patients. Positive for micro and macro metastases lymph nodes in the central lymphatic basin are found in 54. In 46 of them we identified metastases in the ipsilateral, and in 21 in the contralateral central neck nodes. The analysis of patients with lateral metastases found 7 unilaterally and 3 bilaterally. Skip metastases were registered in 4 of these 10 patients. Conclusions. The results of our study show that despite the favorable prognosis and non-aggressive behavior of papillary microcarcinoma, factors attesting to the invasive nature of the tumor occur in 44.5% or almost half of patients. This requires careful and individual approach constructing therapeutic strategy for the treatment of patients with papillary microcarcinoma

Context. Hashimoto’s thyroiditis is the most common autoimmune disorder as cause of secondary hypothyroidism. The disease is associated with several metabolic disturbances and inflammatory disorders. Objectives. The aim of the current report was to evaluate several inflammatory and metabolic predictors of Hashimoto’s thyroiditis. Subjects and Methods. In the current study, forty patients with Hashimoto’s thyroiditis participated in the current study. They were aged between 20 to 50 years old. Anthropometric and nutritional measurements were assessed and biochemical factors including serum VEGF, IL-23, Nesfatin-1 and serum lipids were measured. Results. Waist circumference was higher among patients with lower serum TSH concentrations. Serum HDL and T4 concentrations were lower and serum IL-23 was higher among patients with higher TSH concentrations. BMI, WC and serum HDL were negative predictors of serum TSH while IL-23 was positively associated with TSH concentrations. Serum lipids including TC, TG and LDL were also negatively associated with T3 and T4 concentrations. Conclusions. According to our findings, VEGF and serum IL-23 were potent predictors of Hashimoto’s thyroiditis. However, further studies are warranted to better clarify these associations and underlying pathologic mechanisms.

Objective. The aim of the study was to test whether a correlation exists between the Epworth Sleepiness Scale (ESS) and respiratory sleep parameters in patients with\r\ntype 2 diabetes.\r\nDesign. Subjects and Methods.The records of 83 consecutive patients (mean age 54.6? 9.8 years) with type 2 diabetes\r\nthat accepted to perform an in-hospital sleep study for screening of sleep apnea have been retrospectively evaluated.\r\nResults. There was a weak positive correlation between apnea/hypopnea index (AHI), oxygen desaturation index and ESS, and a weak negative correlation between ESS and mean O2 saturation. When data was separately analyzed in men and\r\nwomen, it could not be identified any correlation between sleep respiratory parameters and ESS in men. In women,\r\ncorrelation coefficients increased, proving a stronger relationship between ESS and AHI (r=0.65, p<0.001), mean O2 saturation (r=-0.52, p=0.005) and oxygen desaturation index (r=0.60, p=0.001). ESS had only a moderate level of accuracy in identifying patients with moderate and severe sleep\r\napnea (sensitivity 84.1%, specificity 74.1%, PPV 84.1%, NPV 74.1%). In women ESS showed a higher sensitivity than in men\r\n(92% vs. 80.6%), but a lower PPV (63% vs.78.1%) in predicting the presence of an AHI &#8805; 15.\r\nConclusions. In women with type 2 diabetes, it is possible to suspect the existence of SAS solely on the basis of the\r\nESS score. In male population, symptoms evaluated by questionnaires, such as the ESS, provide additional information which combined with clinical findings are helpful in selecting patients who are candidates for further detailed sleep studies.

Objective. We aimed to investigate the potential relationship between plasma alarin levels and type 2 diabetes mellitus (T2DM). Patients and Method. We included 154 participants, divided into four groups in a cross-sectional study design. The first group includes patients with T2DM without complications (n=30), the second group patients with T2DM with microvascular complications (T2DMnoC n=32), the third group patients with T2DM with macrovascular complications, T2DM-MV (n=32) and the last group is the healthy control group (n=60). Results. In our study 94 patients were diabetic; 47 females and 47 males. The control group consists of 60 people, 30 women and 30 men. It was found that these had a significant (p>0.05) variation in serum alarin levels among the T2DM (T2DM-noC=3.1±0.7 ng/mL T2DMmV=2.8±0.4 ng/mL, T2DM-MV= 3.6±0.4 ng/mL) versus control group (15.6±2.6). We failed to find a significant variation of serum alarin levels (p>0.05) between T2DM subgroups. Serum alarin levels were significantly higher among control patients (p<0.05). There was no difference between diabetic sub-groups. Conclusion. We concluded that serum alarin levels in patients with T2DM are lower than in normal people. Further studies are needed to investigate the possible prognostic value of alarin in clinical practice in T2DM.

Objective. Few studies are available on the temporal sequence and effect of ethnicity,\r\nsocioeconomic status and environment on pubertal changes leading to sexual maturation in\r\nboys; therefore, we describe normative values for developmental changes in physical and\r\nendocrine characteristics at onset and during progression of the pubertal process in a cohort\r\nof Pakistani boys.\r\nDesign. This cross-sectional study involved 234 healthy, 8-18 years old, school-based boys.\r\nMethods. Body weight, height, appearance of pubic hair patterns and testicular volume\r\n(TV) along with serum FSH, LH, testosterone and GH levels were measured.\r\nResults. Pubarche was first recorded at a mean age of 11.3 years [Tanner stage 2]. TV of\r\n3 ml and the first significant increase in mean serum FSH and LH levels were detected at 10\r\nyears of age. The mean percent increase in TV/year was maximal from 12-14 years, coinciding\r\nwith rising testosterone levels. The levels of gonadotropins increased more than 2-fold between\r\n12-14 years. Whereas, LH continued to increase in postpubertal boys and FSH levels plateaued\r\nat 15 years. GH concentrations were shown to be maximal at 12-13 years and declined\r\nthereafter to prepubertal values. However, BW and height were significantly correlated with\r\nage; yet no significant correlation was seen between body mass index (BMI) and age.\r\nConclusion. The present data among boys indicates an earlier transition to the Tanner stage\r\n2 and an increase in TV, resulting in a slightly more extended period of pubertal development, as\r\ncompared to European and American children pointing to ethnic, social and economic differences.