ACTA ENDOCRINOLOGICA (BUC)

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.

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.

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.

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

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.

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. Even if the last decade brings new information about the existence of the local pulmonary renin-angiotensin system (RAS), published results about its involvement in the progression of various pulmonary diseases remain contradictory. Methods. Using an experimental model of pulmonary allergic disease induced by ovalbumin (OVA) sensitization we studied effects of intratracheal (i.t.) administrated AT1 receptor blocker losartan (LOS) on inflammatory processes supposed to be mediated by pulmonary RAS. Alterations in bronchoalveolar lavage fluid (BALF) cellularity and variations of airway reactivity from OVA sensitized and challenged rats after LOS or vehicle i.t. instillation were comparatively assessed. Results. Blocking of RAS decreased the total BALF cellularity and polymorphonuclear cell count. LOS instillation also reduced the increases in specific airway resistance (sRaw) induced by inhalation of allergen (with 20%) or acetylcholine (with at least 15%). Conclusions. Our data suggest that expressly blocking of local RAS by i.t. administration of LOS have inhibitory effects on allergen - induced lung inflammation and sustain the participation of pulmonary RAS, activated by local or systemic factors, in lung diseases.

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.