ACTA ENDOCRINOLOGICA (BUC)

The mechanism underlying anovulation in the polycystic ovary syndrome (PCOS) remains unclear, although an excessive number of small antral follicles at ultrasound scans and discrepancies with selected follicles sustain the hypothesis of altered follicular development. Anti-M?llerian (AMH) hormone is a member of TGF-b super family of growth factors produced by granulosa cells of pre- and small-antral follicle. The 2 to 3 fold increase in the number of growing follicles in the ovary from PCOS women is reflected by an increase in serum concentration of AMH and thus, this hormone may be a good marker of PCOS.\r\nAim. This study was intended to implement ultra-sensitive ELISA measurement of serum AMH from PCOS women and search for a potential correlation with clinical and laboratory parameters.\r\nSubjects and methods. Sera from patients with PCOS (n = 42) and control women (n = 22) were used for ELISA measurement of AMH (AMH-EIA, Beckman Coulter) with sensitivity of 0.7 pmol/L.\r\nResults. We found a serum concentration of AMH almost 3 folds higher in patients with PCOS compared to controls (73.7 ? 7.5 vs. 25.7 ? 3.9 pmol/L, P < 0.0001). Differences were even higher in lean subjects. A positive correlation was found between total testosterone and LH levels, but not with serum FSH or insulin. Moreover, AMH concentration was correlated to more hyperandrogenic PCOS and with amenorrhea, and thus to the severity of the syndrome.\r\nConclusion. Measurement of serum AMH may be used as a valuable marker for PCOS to confirm diagnosis and evaluate the extent of follicular dysfunction in relation with hyperandrogenism and menstrual disturbances.

The blood-CSF barrier (BCB), as a component of the blood-brain barrier, is protective for the maternal brain. This study assesses estradiol, prolactin, glycoproteic hormones (hCG, FSH, LH, TSH) and thyroxine across the BCB in pregnancy after 38 weeks. Method. 35 pregnant women were simultaneously sampled in serum and CSF during caesarian section and compared to 27 non-pregnant fertile women undergoing surgery for benign gynecological disorders. The study was approved by the local Ethics Committee. Results were analysed as nonparametric variables. Compared to non-pregnant controls, we found high serum estradiol levels at term, also reflected in the CSF, while the CSF/serum ratio was non-significantly modified (median ratio 0.1 versus 0.1, p=NS). Prolactin showed a similar proportional increase in serum and CSF levels at term, with unmodified CSF/serum ratio (median ratio 0.14 versus 0.18, p=NS). hCG showed a similar profile across the BCB. FSH was significantly lower at term, but still conserved the CSF/ serum ratio. LH was undetectable in pregnancy. In peripartum TSH showed a unique profile across the BCB as it was the only one showing an increased CSF/serum ratio compared to non-pregnant controls (median ratio 0.11 versus 0.04, p<0.0001). Thyroxine was significantly increased in both serum and CSF, and showed a CSF/serum ratio unmodified from non-pregnant women (median ratio 0.02 versus 0.02, p=NS). Conclusion. There is an increase of BCB permeablity for TSH in term pregnancy. The peripartum increase in estradiol and decrease in HCG could be involved. We suggest that the unique TSH profile maintains the necessary thyroxine levels in pregnancy at term.

Background. Risk stratification and an appropriate therapeutic approach could be lifesaving in acute pulmonary embolism (PE). Echocardiographic (ECHO) acute right ventricular dysfunction (RVD) is the actual &#8220;gold standard&#8221; in risk evaluation of PE. We previously demonstrated that plasma BNP levels were significantly higher in patients with PE and acute RVD on ECHO vs. patients with normal RV function on ECHO.\r\nAim. Evaluation of the limits of plasma BNP in signalling acute RVD in PE. \r\nMethods. 70 patients with PE were prospectively investigated: 42(60.0%) men, mean ? SD(standard deviation) age 52.51?8.82. BNP was measured on admission using a quantitative fluorescence immunoassay (TriageBNP). ECHO evaluation of the RV function was performed in the first hour after admission. Study protocol was approved by local Ethical Committee. Patients were divided into two groups: group 1-with acute RVD on ECHO, n=24(34.3%) patients; group 2 - without acute RVD on ECHO, n=46(65.7%).Patients from group 1 were further divided into two subgroups: subgroup 1A-admitted in <12 hours after their PE symptoms onset, n=12(50.0%) patients, and subgroup 1B-admitted in >12 hours after the onset of PE symptoms, n=12(50.0%) patients.\r\nResults. BNP proved good in discriminating between patients with and without acute RVD (AUC=0.88, P<0.0001). The cut-off level of plasma BNP=50 pg/mL showed the best sensitivity=0.86 and specificity=0.82 in identifying acute RVD. BNP levels were significantly lower in subgroup 1A (admitted soon) compared to subgroup 1B (admitted later than 12 hours): medians 45.25 pg/mL vs. 344.50 pg/mL, P<0.0001. Eight patients from subgroup 1A, all admitted soon after the onset of their PE symptoms, and all experiencing at least one syncopal episode showed BNP under the cut-off level. In subgroup 1A BNP did not correlate with RV end-diastolic diameter (R=0.23, P=NS), while in subgroup 1B BNP and RV end-diastolic diameter showed a consistent positive correlation (R=0.91, P<0.0001). In subgroup 1A BNP correlated significantly, but negatively, with RV systolic pressure (R=-0.64, P<0.01). In subgroup 1B BNP was significantly positively correlated with RV systolic pressure (R=0.76, P<0.001).\r\nConclusions. BNP higher than a cut-off level of 50 pg/mL could predict acute RVD in patients with PE with a good sensitivity and specificity. Exception of this rule was found in some patients with recent (<12 hours) PE symptoms onset and poor clinical condition.

Background. Pineal and adrenocortical cell morphology, dynamics, hormonal analysis and function in response to both natural and synthetic corticoids awaits in depth investigation in mammals. Aim. To investigate the pineal responsiveness to corticoid treatment from combined morphological and hormonal studies in postpubertal male mice. Material and methods. Three groups, each with 14 mice were used as control (C) or treated with the natural corticoid, hydrocortisone (HYC) at a dose of 4 mg/100 g.b.w. and synthetic corticoid, dexamethasone (DEX) at a dose of 4 mg/100 g.b.w. for ten consecutive days. Results. The treatment induced inverse changes in pineal-adrenocortical karyomorphology, cell proliferation (mitotic percentage M%) and hormonal milieu. Whereas both these corticoids caused pineal stimulation as evidenced from significantly increased nuclear diameter (μm) values (C 3.35 ± 0.05, HYC 4.77 ± 0.02, DEX 4.59 ± 0.04, p<0.001) and cell proliferation (M%) (C 1.11 ± 0.09, HYC 1.59 ± 0.07, DEX 1.44 ± 0.05, p<0.01), the changes induced in adrenocortical nuclear diameter in all the zones (p<0.001), cell proliferation (M%) (C 1.38 ± 0.05, HYC 0.53 ± 0.06, DEX 0.70 ± 0.05, p<0.001) and decreased content of adrenal corticosterone (C 0.24 ± 0.03, HYC 0.13 ± 0.01, p<0.001 DEX 0.15 ± 0.02, p<0.01) were those of adrenocortical inhibition. Conclusion. There exists an inverse relationship between the pineal and adrenocortical functions in post pubertal male mice (Mus musculus).

Introduction. The blood brain barrier (BBB) restricts the transport of hydrophilic molecules such as peptidic pituitary hormones into the brain tissue. The blood-cerebrospinal fluid (CSF) is a part of the BBB.\r\nAim To compare the pituitary hormone levels on the two sides of the BBB in a group of subjects without endocrine diseases.\r\nPatients and methods. We investigated, with the approval of the local ethics committee, 78 subjects without endocrine diseases. Growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) were measured by rapid fluoroimmunoassay with Europium in the blood and cerebrospinal fluid (CSF)sampled simultaneously before rachianestesia for minor surgery.\r\nResults. CSF concentrations are significantly lower than the corresponding serum ones for all hormones studied: 0.04 ? 0.009 mU/mL vs 2.29 ? 0.57 mU/mL for GH, 1.49 ? 0.078 ng/mL vs 10.07 ? 1.42 ng/mL for PRL, 0.57 ? 0.078 U/L vs 22.71 ? 3.65 U/L for FSH, 0.39 ? 0.038 U/L vs 11.11 ? 1.55 U/L for LH and 0.01 ? 0.003 &#956;U/mL vs 1.36 ? 0.17&#956;U/mL for TSH (mean ? SEM; p<0.001). The CSF/serum ratio was below 1 in the vast majority of cases (from all subjects studied we only found 3 cases with supraunitary CSF/serum ratio). The serum and CSF levels were not significantly correlated for\r\nany of the pituitary hormones. Comparing preand postmenopausal women the CSF gonadotropin levels were slightly but nonsignificantly increased after menopause,\r\ndespite marked differences in the serum concentrations: CSF FSH 1.21 ?0.17U/L after vs 0.84? 0.4U/L before menopause, CSF LH 0.60? 0.047U/L after vs 0.43? 0.14U/L before\r\nmenopause. The CSF/ serum ratio for FSH markedly decreased after menopause (0.02?0.003 vs 0.22?0.11) although the effect did not reach statistical significance. The same\r\nwas true for CSF/serum LH ratio (0.026?0.005 vs 0.09?0.002). For none of the hormones studied the CSF levels correlated with age.\r\nConclusion. Pituitary hormones are normally found in the CSF at much lower levels than in the serum. The CSF hormonal\r\nconcentrations do not significantly correlate with the serum ones.

The possibility that a patient with newly diagnosed hypertension has an underlying cause that is directly responsible for the increased blood pressure deserves more attention from clinicians than is currently the case. This limited attention and consideration is responsible for delaying and even missing the diagnosis and proper treatment of secondary hypertension. The reasons are manifold, varying from minimal knowledge of diagnostic tests to easy and low threshold in prescription of antihypertensive drugs. In addition there is the misconception that the prevalence of secondary hypertension is so low that it hardly needs any consideration. However, some forms of secondary hypertension are much more prevalent than previously thought and this applies in particular to endocrine hypertension. In addition, in recent years there are emerging new scientific developments in the field of endocrine hypertension, varying from pathogenesis, genetics, and therapeutics. It is therefore quite remarkable that endocrinologists seem to have hardly any interest in endocrine hypertension, unless there is a clear cut case such as a patient with an already diagnosed pheochromocytoma. They leave the analysis of hypertension to other specialists who have hardly any expertise in for instance the analysis of patients suspected to have primary or pseudo-aldosteronism. The contribution of endocrinology is however essential, not only for detecting more patients with concealed endocrine hypertension but also for optimizing the understanding of the pathogenesis and treatment of high blood pressure in the larger group of patients with primary hypertension.

Context. Oxidative products take part in various physiological processes and overproduction of oxidative products is involved in the etiology of many diseases. Objectives. We aimed to evaluate thiol-disulfide homeostasis (TDH); one of the oxidative stress parameters, in girls with premature thelarche (PT) and precocious puberty (PP). Design. This case-control study was conducted between January 2022 and July 2022. Subjects and Methods. TDH parameters, involving native thiol (NT), disulfide, and total thiol (TT), were evaluated in 39 girls with PT, 41 girls with PP and 46 healthy prepubertal girls. The correlations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) levels with the TDH parameters were determined and ROC curve analysis was performed. Results. NT, TT and NT/TT ratio were higher in the PT and PP groups compared to the control group (p<0.01). Disulfide/NT ratio and disulfide/TT ratio were lower in the PT and PP groups compared to the control group (p<0.05). All the TDH values did not statistically differ between the PP and PT group (p>0.05). There was a positive correlation between LH level, FSH level, and NT level, TT level, NT/ TT ratio. The best parameter to discriminate PT or PT and control groups were NT and TT (p<0.01). Conclusion. TDH is altered in girls with PT and PP. NT and TT levels can be useful to discriminate prepubertal girls with lipomastia and girls with PP and PT in clinical practice. Further studies on larger cohorts of patients are required to clarify our results.

Introduction. Induction of heme oxygenase (HO) gene expression can protect lungs from Hypoxic Pulmonary\r\nVasoconstriction (HPV). Furthermore, there is evidence that Rho-kinase (ROCK) may be involved in HPV. Studies are going on to detect the real mechanisms involved in the phenomenon. Ghrelin, a 28-amino-acid peptide, has been shown that it may protect lungs from HPV side effects. The aim of this study was to evaluate the effect of exogenous ghrelin on HO and ROCK isoforms gene expression during chronic hypoxia (CH).\r\nMaterial and Method.Twenty four adult male Wistar rats were divided randomly in three groups. Hypoxic rats with saline or ghrelin treatment were placed in a normobaric hypoxic chamber (O2 11%), for two weeks. Controls remained in room air. HO and ROCK isoforms gene expression was measured by Real-Time RT-PCR. Lung tissues were histologically processed and stained with hematoxylin-eosin for morphometric analysis.\r\nResults. Morphometric analysis showed that ghrelin reversed the hypoxia induced pulmonary artery wall thickness (P < 0.001). In hypoxic animals, the amount of HO-1 expression increased but there was suppression in HO-2 gene expression (P < 0.05). Both ROCK-1 and ROCK-2 gene expressions were diminished after two-week hypoxia. Ghrelin treatment reduced the overexpression of HO-1 (P < 0.05), but had noeffect on ROCK gene expression.\r\nConclusion. Ghrelin by decreasing the expression of HO-1 and HO-2 in hypoxic animals may be involved in an adaptation\r\nmechanism during CH. However, ghrelin did not change ROCK isoforms gene expression, thus it could not affect HPV in this way. Nevertheless, more studies are needed to justify the protective roles of ghrelin for HPV.

Background. Trigonella foenum graecum L. (Fenugreek, FG) is used in many countries as a medicinal plant. Evidence has suggested the hypolipidemic effect of Fenugreek; however, its actual mechanism has not been determined yet. Objectives. The purpose of our research was to investigate the effect of Fenugreek on lipid profile, liver histology and LDL receptor gene expression in male hamsters fed with high cholesterol diet. Methods. These animals were given normal diet (ND), high cholesterol diet (HCD: 2% cholesterol and 0.5% cholic acid added to ND), HCD supplemented with 2g and 8g fenugreek per 100g ND (HCD+FG2 and HCD+FG8) respectively for four weeks. At the end of treatment, serum lipids, lipoproteins and liver enzymes were measured. Finally, LDL receptor (LDLR) gene expression was determined in the liver of the studied animals using Real Time-PCR method and liver histological changes were evaluated by H&E staining method. Results. A significant reduction was observed in serum triglyceride (p<0.01), total cholesterol, low and very low density cholesterol, aspartate and alanine transaminases in HCD+FG8 group (p<0.05) compared with HCD group, while serum level of HDL-c (p<0.01) increased. In addition, LDLR gene expression in HCD+FG8 group increased 7.8 folds. The results confirm the protection effect of liver tissue in HCD+FG8 group against pathological changes. There was no significant change in LDLR gene expression in HCD+FG2 group. In conclusion, fenugreek ameliorated dyslipidemia by up-regulation of LDLR gene expression and can be used as a protective agent against hypercholesterolemia.

Introduction. Abnormal thyroid function affect spermato-genesis and male infertility. For men, the aromatase deficiency can cause infertility. In this study, the aim is to investigate the effect of maternal hypothyroidism on offspring testicular morphology and cytochrome-P450- aromatase (P450arom) immunoreactivity. Materials and Methods. Eighteen Wistar albino pregnant rats were divided into three groups, namely A, B and K groups. Hypothyroidism was induced by adding 0.01% of propyl thiouracil (PTU) in drinking water. Hypothyroid mothers, group A: given PTU for 21 days during pregnancy, group B: given PTU for 21 days prior to pregnancy; control mothers, group K, given only water. Hypothyroid and control group mothers’ pups at postnatal day (PND) 15 and 60 were sacrificed. We determined immunoreactivity intensity of P450arom and mRNA levels by RT-PCR performed in the testis tissues. ELISA method was used for thyroid function tests for T3, T4 and TSH. Structure of seminiferous tubule was evaluated by hematoxylin-eosin staining. Results. It was seen that the aromatase expression in 15-day-old maternal hypothyroid groups was similar to the one in the control group while there was a decline in the aromatase expression of 60-day-old groups. As for mRNA, it was determined that it had a tendency to increase over time in all groups but this increase was not significant. The tubule diameter and Johnsen’s Testicular Biopsy Score diminished in all hypothyroid groups in comparison to the control group. Conclusion. The changes that occur in the early period of testis development due to maternal hypothyroidism negatively affect testis development in the next stages of life. This situation leads to a decline in aromatase expression in the following years.