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.

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.

Purpose. To re-examine our clinical practice and review strategy for treatment of primary hyperparathyroidism in patients with multigland disease. Methods. Retrospective analysis of 121 consecutive primary hyperparathyroidism (PHPT) patients who underwent surgery in a tertiary center between January 2010 and December 2014. Results. Of 121 patients with PHPT 87% had single gland adenoma (SGD) and 13% had multigland disease (MGD). The overall cure rate was 95.86%. MGD was more frequent in younger persons (<40y)(50% vs. 13.2%). All patients had SPECT-CT (Single Proton Emission Computerized Tomography) with 28% being SPECT-CT negative. Patients with MGD had a higher rate of persistent disease (13.33% vs. 2.83%). Specimen weight was <600mg in 75% of MGD patients. 67% of SPECT-CT negative patients had mild hypercalcemia (Calcium <2.75 mmol/L) which was more frequent in MGD patients (43% vs. 19%). Conclusions. MGD patients were more likely SPECT-CT negative (40% vs. 25.4%) and benefit from bilateral neck exploration (BNE) (74%). However, most SPECT-CT negative patients still have a single adenoma. In our series MGD was more frequent in younger patients, more likely SPECT-CT negative, often associated with mild hypercalcemia and had a higher persistence rate than SGD. BNE is the operation of choice in young, SPECT-CT negative patients. If ultrasound parathyroids suggests a single large adenoma, minimally invasive parathyroidectomy with intraoperative PTH monitoring can be considered.

Purpose. Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). Methods. In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student’s t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman’s test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. Results. Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). Conclusions. In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Background. Autoimmune thyroid diseases (AITD) including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are complex genetic diseases. TSHR is considered as candidate gene in GD. This finding prompted us to investigate the association of TSHR gene polymorphism with the risk and the prognosis of AITD in Tunisia. Methods. A total of 84 healthy controls and 91 patients with AITD (69HT and 22 GD) were genotyped for TSHR rs74067403A>G polymorphism and 134 healthy controls and 149 patients with AITD (98 HT and 51 GD) were genotyped for TSHR rs1054708 T>C polymorphism. Results. For rs1054708, we found an association between HT, AITD and the heterozygous genotype TC, the mutated genotype CC and the genotypes presented the mutated allele C (TC+CC) and with mutated allele C. The heterozygous genotype TC and the genotypes that presented the mutated allele C of rs1054708 are associated with male patients with AITD evenly the heterozygous genotype TC is associated with age of onset of disease. Conclusions. These preliminary results suggest that TSHR rs1054708 polymorphism may be a protective factor against HT and AITD. This polymorphism can affect the etiology of AITD between men and women and also by age.

effects of Ultrasonic Coagulation (UC), Bipolar Energy Sealing System (BESS), Intra Operative Nerve Monitoring (IONM) and surgical experience on the complications of thyroid surgery. Method. The data of 1627 patients who underwent thyroid surgery for various indications in our department between 2009 and 2018 were analyzed retrospectively and the effects of different technological devices on complications were investigated. Results. Transient recurrent laryngeal nerve (RLN) palsy was higher between 2009 and 2013, when IONM was not in routine use (p=0.029). There were no significant differences between two energy devices (UC and BESS) in terms of transient or permanent RLN palsy, bleeding, and transient or permanent hypocalcemia. Multivariate analysis showed that young age (0.006), female gender (0.016), surgery type (p<0.001), and lateral neck dissection (p=0.026) are independent risk factors for transient hypocalcemia. Conclusion. The results indicate that there is no superior hemostatic device. IONM and specific branching decrease transient RLN palsy. Female gender, young age, completion thyroidectomy, and lateral neck dissection were independent risk factors for the development of transient hypocalcemia.

Objectives. Despite extensive research on endometrial cancer (EC) and endometrial hyperplasia, there is still a gap in understanding the molecular mechanisms underlying their development and progression. The aim of this study was to investigate the expression levels of FOXO-1, P27Kip1, miR-27, and miR-186, and Akt1, Akt-P proteins in patients with EC and endometrial hyperplasia compared to control subjects. Subjects and methods. Samples of the endometrial tumor (n=30), normal (control) (n=30) and endometrial hyperplastic (n=30) tissue were obtained from patients referring to Arash and Imam Khomani hospitals, Tehran, Iran. Expression levels of genes and microRNAs were evaluated by qRT- PCR. Western blot analysis was applied for protein evaluation. The data were analyzed using t-test, Mann -Whitney U, Pearson correlation coefficient analysis, ANCOVA and ANOVA. Results. There was significant decrease in FOXO-1 in EC tissue compared to control tissue (p<0.05). Significant increase was observed in expression of miR-27 in patients with EC (p<0.001) and hyperplasia (p<0.01), whereas miR-186 expression level increased significantly only in patients with EC (p<0.05). P27Kip1 expression level did not significantly change in patients with EC and hyperplasia. There was a significant association between expression levels of miR-27 with FOXO-1 and P27Kip1 in patients with EC. Western blot analysis revealed higher endometrial AKT1-P protein levels in patients with EC and hyperplasia than control subjects (p<0.05). Conclusions. Our findings suggest that FOXO-1, miR-27, miR-186, and Akt1-P/Akt1 protein have the potential to serve as tissue biomarkers for early diagnosis, prognosis, and progression of EC in the human reproductive system.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is widely used for the standardized reporting of thyroid fine-needle aspiration (FNA) cytology. The 2023 revision of TBSRTC introduced specific subcategories for the classification of atypia of undetermined significance (AUS). This study tests the association between AUS subtypes and malignant diagnoses, namely AUSnuclear atypia and AUS-other, in archived thyroid – FNA specimens with atypia from 2018-2022 at King Abdulaziz University Hospital. A total of 104 thyroid – FNA specimens with AUS were re-evaluated cytologically and correlated with subsequent surgical outcomes, along with a discussion of discrepant cases

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.