ACTA ENDOCRINOLOGICA (BUC)

Introduction. The aim of this study is to appreciate the visual and endocrine outcome and to determine the factors that may influence the outcome of patients with pituitary apoplexy. Material and Methods. Between January 2006 and March 2012, 81 pituitary tumors were treated at “N. Oblu” Clinical Emergency Hospital in Iasi. Investigations of 22 of these cases met the criteria for pituitary apoplexy (17 cases of non-secreting pituitary adenomas and 5 cases of secreting tumors (4 GH secreting adenomas with acromegaly and 1 prolactinoma). Twenty one patients underwent surgery. The mean follow-up duration was 21 months. Results. Distribution between sexes was 1:1, with a mean age of 55.0 years. In all cases pituitary apoplexy emerged in patients with macroadenomas (>1cm). 77.27% presented decreased visual acuity, cranial nerve palsy was found in 45.45%. Visual acuity improved after surgical decompression best results being obtained in patients operated within first 7 days from onset (p=0.005); 80% recovered the CN palsy after surgery (p=0.005), with no relation to delay of surgery (p=0.26) or cavernous sinus invasion (0.095); 18.18% presented with pituitary deficiency and maintained it after surgery, the rate of new pituitary deficiency was 27.77% significantly higher in patients operated using craniotomies (p=0.001). Conclusions. Clinical apoplexy emerged in patients with macroadenomas unrelated to the tumor type. Early surgical decompression (< 7 days) and high dose corticoids represent the main therapeutic approach for obtaining good recovery of visual function. CN palsy has a good prognostic not being related to the delay of surgery. Pituitary dysfunction at presentation is irreversible and has a high occurrence after surgical decompression, requiring lifelong hormone replacement.

Context. Hypothyroidism and iron deficiency are among the most common pathologies in population. Therefore, there are a lot of patients assuming both iron salt supplements and levothyroxine therapy. Objective. To evaluate the effect of iron salt intake on L-T4 absorption among different L-T4 formulations. Materials and methods. A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies and reviews written in English and published online up to 21 December 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. Results. The data show an impaired absorption of L-T4 in tablets formulation when taken concomitantly with iron salt supplements. These phenomena seem to be circumvented by new L-T4 formulations. Conclusion. Liquid L-T4 formulations can be ingested with iron salts, with no impairment of absorption. More studies are necessary to confirm these data for soft-gel capsules L-T4.

Context. There is no consensus regarding routine usage and benefits of molecular markers for prediction of prognosis and assessment of risk groups in differentiated thyroid cancer (DTC). Objective. We aimed to investigate NIS, Galectin-3, PTEN, P53 and Ki67 expressions in tumor tissue and metastatic lymph nodes in PTC and their association with lymph node metastasis and prognosis. Material and Methods. Ninety two papillary thyroid cancer patients who underwent total thyroidectomy and central lymph node dissection were included in this study. NIS, Galectin-3, PTEN, P53 and Ki67 immunohistochemical stainings were performed for all surgical tumor tissues and metastatic lymph nodes of the 38 patients. Age, gender, tumor size, multifocality, capsular invasion, extrathyroidal extension and lymphocytic thyroiditis were assessed retrospectively. Results. Seventy three females (79.3%) and nineteen males (20.7%) were included in this study. Risk of lymph node metastasis was higher in tumors with capsular invasion and extrathyroidal extension (p=0.03 and p < 0.001). NIS, PTEN and Galectin-3 protein expressions in tumor tissue were not associated with gender, tumor size, multifocality, extrathyroidal extension, capsular invasion, lymph node metastasis and tumor recurrence. Mean Ki 67 proliferation index was 2.08±0.95%. Ki 67 proliferation index was associated with tumor size (p=0.012). Intensity and expression of NIS and PTEN in tumor tissue were concordant with intensity and expression in metastatic lymph nodes (p<0.001). Ki 67 proliferation index in tumor was concordant with metastatic lymph nodes (p=0.02). Conclusions. NIS, PTEN, Galectin-3, Ki67 and P53 expressions were not associated with the risk of lymph node metastasis in PTC patients. Routine analysis of these markers does not seem to be favorable. Further studies with new markers are necessary to determine prognostic predictors.

Objective. The extremely negative effects of diabetic neuropathy over the entire human organism make the detection of modifications in early stages very important. Introduction. The purpose of this study is to establish a correlation between early modifications appeared at the level of corneal nerves fibers and the glycemic values of patients with type 2 diabetes. The affection of corneal nerves fibers has been emphasized with the help of corneal confocal microscopy (CCM). Method. A total number of 70 subjects have been evaluated of which 55 suffered from type 2 diabetes (group A) and 15 have been subject to control (group B). The ophthalmologic control also contained a confocal microscopy that has highlighted the decrease of the number of nerves filets of the sub-basal plexus, modifications associated with type 2 diabetes. Results. The density of nerves fibers (12.11± 1.064 n/mm2 compared to 28.33 ± 2.101 n/mm2, P= 0.001); the density of nerves branches (29.94 ± 3.980 n/mm2 compared to 43.75 ± 4.605 n/mm2, P<0.001); the length of nerves fibers (11.77 ± 0.638 mm/mm2 compared to 17.82 ± 0.479 mm/mm2, P=0.002), the total density of nerves fibers (23.25 ± 3.213 n/ mm2 compared to 63.75 ± 8.278 n/mm2, P=0.042) and the area of corneal nerves fibers (0.0044 ± 0.000247 mm2 /mm2 compared to 0.007893 ± 0.00054 mm2 /mm2, P=0.014) have been significantly smaller in patients with diabetes compared to healthy subjects. Conclusions. Being a non invasive technique, corneal confocal microscopy represents a technique that can be easily used in the detection of early modifications of fibers of subbasal corneal nerves stratum, in the case of patients suffering from type 2 diabetes.

Context. Arterial stimulation and venous sampling (ASVS) is the most sensitive diagnostic method for occult insulinoma localization. We present our experience with this method and modifications used that proved to ensure greater safety and sensitivity with this rare pathology. Relationship between tumour size and changes in peak insulin values and release curves were also tested. Subjects and Methods. Six consecutive patients with biochemically established diagnosis of endogenous hyperinsulinism underwent preoperative non-invasive diagnostic tests with sensitivities calculated and compared for all methods. Certain modifications were used in ASVS procedure that included hepatic vein catheterization, order of arterial stimulation, time intervals between each stimulation, diagnostic insulin gradient level and the time frame for diagnostic rise of insulin. Peak insulin values and insulin gradients were compared with tumour size in each patient. Results. In all patients, calcium stimulation accurately localized the insulinoma, with higher sensitivity than any other method. A more than 4-fold increase in insulin level was observed in all patients, after injection into the tumour feeding artery, while 2 to 4-fold increase was observed in the tumour neighbouring areas. Tumour size showed an inversely proportional correlation to peak insulin values in each artery that correctly located the tumour. Conclusion. ASVS presents the most accurate and safe method for localization of occult insulinomas. A four-fold insulin gradient can be used as a limit for positive preoperative localization in order to secure a higher specificity.

Background. In most type 1 and mixed forms of amiodarone-induced thyrotoxicosis (AIT), after restoration of euthyroidism and whether amiodarone can be withdrawn, an ablative therapy (thyroidectomy or radioiodine) is required. Radioiodine ablation of the thyroid was reported to prevent recurrence of AIT after amiodarone reintroduction.\r\nAims. To assess the efficacy and safety of radioiodine treatment in type 1 and mixed forms of AIT.\r\nPatients and methods. 9 patients (6M/3F) with type 1 and mixed form of AIT, mean age 62.2 ? 13.3 years (range: 50-85 years), pretreated with methimazole, received radioiodine treatment. The underlying thyroid disease was Graves disease (n= 5), toxic multinodular goiter (n= 3) and toxic adenoma (n=1). TSH, total T3, total T4, free T4, TPOAb were measured by radioimmunoassay; radioiodine uptake, thyroid ultrasonography, color flow Doppler ultrasonography were performed.\r\nResults. Multiple radioiodine doses were required in 4 out of 9 patients. Pretreatment 24 hours radioiodine uptake exceeded 10% in 12 out of 16 doses. Mean cumulative dose was 23.17 ? 17.48 mCi 131I (range 6-50 mCi). The period between amiodarone withdrawal and 131I administration was 11.72 ? 12.45 months (range: 2-41 months). Mean cumulative 131I dose was higher in AIT due to toxic multinodular goiter and toxic adenoma (30.25 ? 20.09, range: 11-50 mCi) versus Graves disease (17.5 ? 14.76, range: 6.5-40 mCi). In one patient with toxic adenoma, thyroidectomy was contraindicated due to a comorbidity-central core disease - a non-progressive congenital myopathy, associated with an increased risk for malignant hyperthermia. Hypothyroidism occurred in all patients but one (euthyroid), within 14 ? 3 months (range: 5-27) after the first radioiodine dose. Sinus rhythm was restored in 3 out of 5 patients. One case of radiation thyroiditis occurred after a single 6.5 mCi 131I dose.\r\nConclusion. Radioiodine ablation therapy is an effective and safe alternative in patients with type 1 and mixed forms of amiodarone-induced thyrotoxicosis. Since amiodarone should need sometimes to be restarted, post radioiodine hypothyroidism should be viewed as a goal rather than a complication.

Background. Evaluation of features of puberal maturity on a representative specimen of adolescents from Mures county.\r\nMaterial and method. The collected data came from the Public Health Authority in 2008, from 2013 teenagers, with ages ranging between 11&#8211;18 years, according to the Physical development registration file, Tanner stages and demographic data.\r\nResults. Boys grew at a faster rate in both height and weight than girls. In the urban areas, there is a preponderence for children in Tanner stages I-IV, compared to Tanner stage V. In the rural area, girls from middle school cover stage I then stage V of development and boys prevail in stage III and decrease in stage V. The teenagers of Mures county between 15-18 of age, both boys and girls, have a higher frequency than the rest of the teenage population of the country in stage V development, and for ages between 11&#8211;14 there is a majority for stage I. Correlating the parent&#8217;s education level and the puberal maturation of teenagers, we concluded that elementary and medium education levels prevail for all Tanner stages involved, without significant differences between them. Late puberty is more frequently associated to the parent&#8217;s elementary education level (68.34%) and rural area, in both genders. In the rural area there is a higher preponderence of children with rank over 2, due to the tendency of families in the urban area to reduce the children&#8217; number in the past years. Out of the entire study group, 3.75% were disharmonious with obesity: 3.94% of boys and 3.56% of girls, with a slight predominance in younger girls. There is no significant correlation between obesity and birth weight (p=0.441) or between puberal maturity level and weight.\r\nConclusion. We must stress upon the importance of monitoring the aspects of physical, neuropsychic development and puberal maturity in children, considered influence factors of morbidity.

Context. Predictive equations estimate total fat mass obtained from multiple-site ultrasound measurements; however, the predictive equation of total fat mass has not been investigated solely from abdominal subcutaneous fat thickness. Objective. To develop regression-based prediction equations using abdominal subcutaneous fat thickness for predicting fat mass, and to explore the validity of these predictive equations. Design. Cross-sectional study. Subjects and Methods. Twenty-seven males and eighteen females were randomly divided into two groups as the model prediction and the validation. Total body fat mass was determined by dual-energy X-ray absorptiometry. The linear regression analysis was used to predict equations for total body fat mass from abdominal subcutaneous fat thickness acquired by ultrasound. Then, these predictive equations were tested on the validation group. Lin’s concordance correlation coefficient (CCC) was used as a further measure of agreement. Results. When fat mass prediction equations were tested on the validation groups, measured- and estimated-total fat masses in males (p=0.9) and females (p=0.5) were found similar. A good level of agreement between measurements in males (CCC=0.84) and females (CCC=0.76) was attained. Conclusion. The abdominal subcutaneous fat thickness obtained from a single region by ultrasound might provide a non-invasive and quick evaluation.

Context. Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy. It is also a growing problem worldwide and is associated with many maternal and fetal complications during and after pregnancy. Objective. This study aimed to investigate the neonatal and maternal complications of gestational diabetes in the Iranian population of pregnant women. Design. This prospective cohort study was carried out on the health assessment data of pregnant women in the age range of 18-45 years who were referred to health centers affiliated with Mashhad University of Medical Sciences, Mashhad, Iran, from March 2019 to September 2020. Subjects and Methods. Overall, 2,500 pregnant women with GDM and 7,700 healthy pregnant women were enrolled in the GDM and healthy groups, respectively. Individuals’ data were recorded in an electronic health record system (SINA System) and were later collected and analyzed. Results. Significant between-group differences were observed in terms of cesarean delivery risk, hypertension, fetal macrosomia, preeclampsia, preterm birth, fetal birth weight, and neonatal icterus in GDM and non-GDM groups. However, no significant differences were found in terms of stillbirth, and low birth weight between the two groups. Based on the logistic regression model, GDM significantly increased the risk of cesarean delivery, fetal macrosomia, and neonatal icterus. Conclusions. The fetal macrosomia leading to the cesarean delivery, and neonatal icterus were determined as the significant complications of GDM in the Iranian population. These results can provide valuable insight into healthcare planning.

Context. Sodium Glucose Co-Transporter-2 inhibitors (SGLT2i) are oral antidiabetic agents that can be used with insulin in the treatment of type 2 diabetes mellitus, known for cardiovascular and renal benefits. Dapagliflozin and empagliflozin are available in Turkey and we aimed to evaluate real-life data of using these two molecules with other oral antidiabetic drugs (OAD) or insulin. Subjects and methods. 119 patients (59 women, 60 men) files who had started SGLT2i between 2017-2019 were examined retrospectively until 6 months after the treatment change. Patients’ weight, body mass index (BMI), insulin doses, fasting blood glucose, HbA1c, lipid profile, spot urine albumin/creatinine ratio, e-GFR values, ALT, AST, uric acid levels were evaluated at baseline, 3 months and 6 months. Results. 41.2% of patients were using dapagliflozin and 58.8% were using empagliflozin. After 6 months of follow-up, HbA1c decreased from 8.27% to 7.45% (p<0.001). Daily total insulin dose decreased from 84.75 to 75.58 U/day in 3 months (p<0.004). Weight and BMI decreased significantly at 6 months. ALT, AST decreased significantly in patients using insulin (p 0.001 and 0.007), whereas spot urine microalbumin/creatinine ratio decreased at 3 and 6 months (p 0.005 and 0.020). A significant decrease was also observed in uric acid levels (p: 0.026). Conclusions. Dapagliflozin and empagliflozin have beneficial effects on decreasing glycemic parameters, weight, transaminases, uric acid and microalbuminuria in the real life environment. We also observed that SGLT2i and insulin combination is as safe and effective as combination with OAD.