ACTA ENDOCRINOLOGICA (BUC)

Context. Type 2 diabetes is a chronic metabolic disease which affects bone. There is evidence in the literature about some serum markers that reflect the bone turnover metabolism, such as RANKL (Receptor Activator of Nuclear factor Kappa-b Ligand) and Fibroblast Growth Factor (FGF) 23. Objective. We aimed to investigate the correlations between RANKL and FGF23 and other diabetes-related factors possibly influencing early bone turnover changes. Subjects and Method. We conducted a crosssectional analytical study on a group of 171 patients with type 2 diabetes, without Charcot’s arthropathy or a history of amputations, in which a complete history and anthropometric, clinical, biochemical and dietary evaluation were performed. We evaluated the serum level of RANKL and FGF 23. Results. RANKL was significantly lower in patients with macroangiopathy (0.42±0.15 pmol/L vs. 0.47±0.2 pmol/L, p=0.001). The level of FGF23 was lower in patients with neuropathy (0.37±0.36 pmol/L vs. 0.41±0.17 pmol/L, p=0.001). We found that FGF23 increased with age, but decreased with the duration of diabetes. We also found an inverse relationship between FGF23 levels and HbA1c, triglycerides, diastolic blood pressure, total proteins, albuminemia. Conclusions. RANKL was significantly lower in patients with macroangiopathy, and FGF 23 in patients with neuropathy. Therefore, more studies are needed to elucidate their role in early bone turnover changes.

Context. Cardiomyopathy is the most frequent cardiovascular complication in acromegaly. Objective. We aimed to compare some echocardiographic markers in acromegaly patients with controls and find a correlation with disease duration, disease activity, levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Design. We conducted a cross-sectional casecontrol study for the period of 2008-2012. Subjects and methods. Acromegaly patients altogether 146 (56 men and 90 women), were divided into four groups according to disease activity and the presence of arterial hypertension (AH). The control group included 83 subjects, matching the patient groups by age, gender and presence of AH. GH was measured by an immunofluorometric method, while IGF-1 by IRMA method. All patients and controls were subjected to one- and two-dimensional transthoracic echocardiography, color and pulse Doppler. Results. We found a thickening of the left ventricular walls and an increase in the left ventricular mass. However, these changes were not statistically significant in all groups and no correlation with disease duration could be demonstrated. As markers of diastolic dysfunction, increased deceleration time and isovolumetric relaxation were registered, which were dependent mainly on age in a binary logistic regression analysis, but not GH or IGF-1. Using absolute values, ejection and shortening fractions were increased in some groups. Using cut-off values, a higher percentage of systolic dysfunction was demonstrated in patients compared to their corresponding controls. Engagement of the right heart ventricle was also found – increased deceleration time and decreased e/a tric ratio. Conclusions. In conclusion, functional impairments of both ventricles were present, with a predominance of left ventricular diastolic dysfunction.

Introduction. Salusins are multifunctional endogenous peptides shown in human and rat tissues. Serum salusin α level is decreased in coronary artery disease and lack of salusin α enhances coronary atherosclerosis. Hypothyroidism is a chronic inflammatory disease that has a high risk of developing cardiovascular disease. Here we aimed to search the relationship of overt hypothyroidism and subclinical hypothyroidism with salusin α and other inflammatory markers, also the effect of L-thyroxine treatment on these findings. Material and Methods. 32 patients with overt hypothyroidism taking L-thyroxine treatment, 18 patients with subclinical hypothyroidism without treatment and 25 healthy patients as control group were included in the study. Serum salusin α, TNF α, sCRP, glucose, insulin and lipid levels were tested for all groups and results were evaluated with SPSS statistical analysis method. Results. HDL, sCRP, salusin mean values were statistically significantly different in all 3 groups. HDL level was statistically significantly higher in control group compared to treatment group. sCRP level was higher and salusin level was lower in both treatment and non-treatment hypothyroidism groups compared to control group. When treatment and non-treatment hypothyroidism groups were compared, there was no statistically significant difference for salusin α, but HDL level was high and insulin level was low statistically significant in treatment group. Conclusions. Salusin α that is shown to be protective for coronary artery disease and hypertension, is found to be significantly low in hypothyroidism, thus it is a marker that increases the cardiovascular disease risk in this specific patient group.

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.

Objective. To evaluate obstetric and neonatal outcomes of patients with type 1 diabetes mellitus (T1DM) and compare multidose injection (MDI) and continuous subcutaneous insulin infusion (CSII). Study Design. Retrospective study of 53 pregnant patients with T1DM reaching at least 24th gestational week. Results. Fourteen patients (26.4%) hospitalized for insulin dose regulation. Ten patients had hypertensive diseases. Perinatal mortality occurred in 2 neonates owing to cardiac malformations. Neonatal hypoglycemia, small for gestational age, large for gestational age, and neonatal jaundice were demonstrated in 8, 4, 12 and 19 newborns, respectively. Sixteen newborns were admitted to the NICU for various reasons. Congenital malformations were detected in 7 newborns (6 cardiovascular and 1 central nervous system anomaly). Despite lack of statistical significance, total daily insulin doses were higher in the MDI group than in the CSII group with doses of 62 IU (18–166) and 51 IU (20–114), respectively (p=0.119). Gestational and perinatal outcomes also showed no statistical significance. However, all congenital abnormalities and perinatal deaths occurred in the MDI group. Conclusion. T1DM in pregnancy is a challenging problem in terms of having better obstetric and perinatal results. CSII may be used safely instead of MDI in appropriate patients.

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. 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.

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.