ACTA ENDOCRINOLOGICA (BUC)

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.

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.

OBJECTIVES: This study was carried out on 1290 patients, whose choroids plexus and pineal gland were examined on computed tomography. Aim: To check the correspondence between the choroid plexuses and the pineal gland calcifications along age groups and sex; and the connections between these calcifications and associated pathology.\r\nMATERIALS AND METHODS: The study group consisted of patients of both sexes, within six age intervals.\r\nRESULTS: In order to classify the calcification variants, eight types of combinations were ordered and can be seen in CT: two refer to extreme variants: totally uncalcified (type 1) and totally calcified (type 8); bilateral, symmetrical variants (types 4 and 5); the other four types include the asymmetrical calcifications (2, 3, 6 and 7). After the anthropological study the results demonstrate that there are significant differences between calcification of the choroids plexus and those of the pineal gland with the two sexes, on age groups and pathological ground. For type 1-totally uncalcified the maximum frequency is around 70% with ages under 19. For type 8 - totally calcified, bilateral, the maximum frequency is around 50% with age groups 48-59 and 60-71. For type 4 - calcification only of choroid plexus, one finds a continuous increase from about 10% at the first age group to about 25% at the last group, while for type 5- calcification only of the pineal gland the frequency is 10%&#8722;20%. We started from the hypothesis that the presence of these calcifications is physiological, and has an active adaptative metabolic part depending on many factors, among which the individual constitutional ground is also present.\r\nCONCLUSIONS: The age is not the main cause of the calcification types, but a process of adaptative-reactive variability of interface type, playing an integrating mediating part.

At least one fifth of pituitary adenomas exhibit plurihormonality when using immunohistochemistry for anterior pituitary hormones. However, the correlation with clinical features is weak, without an agreement upon pathological predictors of tumor behavior. The aim was to determine the immunoreactivity for anterior pituitary hormones and alpha subunit in 276 consecutive pituitary adenomas patients, aged 22-79 years (44.3 ? 8), 154 F/ 122 M: 83 acromegalics (ACM), 173 nonfunctioning adenomas (NFA) and 20 prolactinomas (PRM) submitted to surgery via transfrontal (81) or transsphenoidal (195) along 10 years (1995-2005). In addition, clinical data, hormonal secretion and tumour size were evaluated before pituitary surgery. Local ethical committee approved the study design. The immunoreactivity performed by the avidin-biotin-complex method was evaluated for beta FSH, LH, TSH, alpha subunit, PRL and GH, using a semiquantitative scale of stained cells: strong (>20%), positive (10-20%), weak (5-10%) and negative (<5%). CT or MRI tumor size (less than 1 cm, 1-2 cm, 2-4 cm and over 4 cm on maximal diameter) were considered together with the Hardy neuroradiological stage. The results showed that 16/83 ACM, 53/173 NFA and 4/20 PRM exhibited immunoreactivity for beta FSH and LH. TSH immunoreactivity was positive in 13/83 ACM, 11/173 NFA and 1/20 PRM. Tumor size in gonadotrophin - positive group (> 10% of stained cells) was between 1-2 cm in 6 ACM, 21 NFA and 2 PRM, while positive bigger tumors (2-4 cm) were in 7 ACM, 24 NFA and 2 PRM. Giant, over 4 cm tumors were positive in 3 ACM, 8 NFA and no PRM. A similar trend of the tumor size distribution was observed in the monohormonal or null cell adenomas. In conclusion, tumor size and gonadotrophin plurihormonality are independent factors in the management of pituitary adenomas.

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).