ACTA ENDOCRINOLOGICA (BUC)

We studied the incidence, risk factors, presentation, treatment and prognosis of calcific uremic arteriolopathy (CUA) in 140 of our hemodialysis patients. Methods. Patients with CUA in the past 3 years have been compared to controls in a cross-sectional survey of 140 hemodialysis patients. Results. Prevalence of CUA was 6/140 (4.28%); common presentation was ulcerated acral necrosis. Age, sex ratio, BMI, prevalence of diabetes were similar in case (n=6) and control (n=134) patients. CUA patients had higher serum calcium (9.58?1.25 mg/dL vs. 8.50?1.03 mg/dL, p=0.01), calcium-phosphate product (71.06?19.67 mg2/dL2 vs. 58.73?17.20 mg2/dL2, p=0.01) and parathormone levels (1854?1407 pg/mL vs. 654?776 pg/mL, p=0.0002). Differences in ingestion of calcium, active vitamin D and non-calcium containing phosphate binders in the year prior to the assessment were not significant. CUA patients had higher CRP values in the 6 preceding months than non CUA patients (6.61?9.68 mg/dL vs. 1.97?4.20 mg/dL, p=0.01); logistic regression disclosed CRP as the only predictive factor for CUA (p=0.03). 4 (66%) of the CUA patients died due to sepsis, as compared to 3(2.23%) of the control group (p=0.001). 2 of 3 parathyroidectomised patients survived. In conclusion, this is, to our knowledge, the first series of CUA reported from Eastern Europe. In our center acral, ulcerated forms of CUA in patients with severe hyperparathyroidism are predominant.

Background: Salivary monitoring of hormone levels has many advantages over the more conventional serum/plasma analysis. Salivary free metanephrines (MN) and normetanephrines (NMN) could precise biochemical diagnosis of pheochromocytoma (PHEO) as an alternative to plasma metabolites.\r\nSubjects and methods: The prospective case-control study included a group of 30 patients confirmed with PHEO an age-matched control group of 70 normotensive subjects. The PHEO diagnosis was suspected on clinical ground and confirmed by imaging studies and classical neuroendocrine markers. Free plasma and salivary NMN and MN were assayed using enzyme immunoassay for both metabolites.\r\nResults: In tumor cases all metabolites were increased. As expected, values for all 4 parameters (mean?SEM) differed significantly in tumor group vs. normal group: free plasma\r\nnormetanephrines (NMNp): 1514.16 ? 282.97 pg/mL vs 47.82?2.52 pg/mL; free salivary normetanephrines (NMNs):\r\n663.63?168.47 pg/mL vs 44.98? 2.47 pg/mL; free plasma metanephrines (MNp): 445.20 ? 99.92 pg/mL vs 18.87?1.03\r\npg/mL; free salivary metanephrines (MNs):206.60?91.48 pg/mL vs 14.47?0.72 pg/mL with significant correlations in all\r\n100 subjects. Passing & Bablok regression showed no significant deviation from linearity in Elisa assay of NMNs vs NMNp; a significant deviation from linearity existed\r\nin Elisa assay of MNs vs MNp. Cut-off values, sensitivity and specificity for all 4 parameters were calculated by ROC\r\nanalysis. Plasma and salivary normetanephrines proved similar sensitivity (100%) and specificity (100%). Pairwise\r\ncomparison of ROC curves areas showed no significant differences between NMNp vs NMNs and MNp vs MNs. Ten cases were investigated post-surgery. All 4 parameters\r\nshowed no significant differences vs. control group.\r\nConclusions: Salivary free normetanephrines could be used as a nonstressful marker for diagnosis purpose in pheochromocytoma proving similar sensitivity and specificity as plasma free normetanephrines.

Objective. In postmenopausal period, changes in bone turnover markers (BTM), vitamin D3, cytokines and parathyroid hormone (PTH) are frequently observed. The study was to assess bone mineral density (BMD) and bone metabolism index (IBM) in the perimenopausal women. Design years: 2013-2014. Subjects and Methods. One hundred and thirteen women were divided into four groups: group I (35 not menstruating 50 - 60 years old with osteoporosis), II (23 not menstruating 50 - 60 years old without osteoporosis), III (30 menstruating 40 - 49 years old with osteoporosis), IV (25 menstruating 40 - 49 years old without osteoporosis). The following parameters were measured: IL-1β, IL-6, TNF-α, hormone oestradiol (E2), PTH, FSH, TSH, calcium (Ca2+), phosphates (P), alkaline phosphatase (bALP), C-terminal telopeptide of type I collagen alpha 1 chain (α1CTX), osteocalcin (OC), BMD, IBM. Results. IBM and BMD were significantly lower in premenopausal than in postmenopausal women. The concentration of OC, CTX, 25OH D3 and PTH levels differed significantly between group I vs. II, group I vs. III and group II vs. IV. Conclusions. The levels of BTM, D3, PTH differed significantly between groups. This study demonstrated that bone metabolism depended mainly on processes related with menopause state and changes in D3, PTH and cytokines levels.

Context. Diabetes is a chronic disorder with a complex pathogenetic background including monogenic, polygenic, and environmental causes. Objective. The aim of the present paper is to share the information related to genetic and clinical data of large pediatric diabetes cohort. Design. The present study retrospectively analyzes genetic and clinical findings of subjects diagnosed with diabetes under the age of 18 year and are in follow-up in a pediatric diabetes referral center. Subjects and Methods. Out of 1205 children with diabetes (902 treated with insulin) 246 underwent genetic tests on the basis of clinical selection criteria since 2007. Results. One hundred and ten variants related to diabetes were found in 89 of them. Age at presentation was 9.5±4.02 years (F/M 44/45). In total 49 pathogenic and likely pathogenic, 11 “hot and warm” of unknown significance variants were found in fourteen MODY and fifteen non- MODY genes according to criteria developed by American College of Medical Genetics. Thirty novel mutations were found. GCK (26.6%) and ABCC8 (10%) were two most frequently affected genes. Antibody testing revealed negative results in 80% of cases. Conclusions. Genetic interpretation in selected cases is important to understand the nature of the disease better. Improvement in testing opportunity and awareness might increase the prevalence of genetically explained diabetes cases. The distribution of subtypes differs between countries and even regions of the same country.

Context. Stress hyperglycemia has been studied in numerous critical illnesses for several decades. Despite the extensive accumulation of knowledge about this topic, the definition of stress hyperglycemia is not updated since 2007. Subjects and Methods. We performed a narrative review about stress hyperglycemia in acute myocardial infarction (AMI), aiming to improve its current definition and to give evidence supporting this. Results. The definition of stress hyperglycemia in 2021 we recommend is: “SH is a high ABGly in an AMI patient irrespective of DM status. It can be calculated as e.g., “stress hyperglycemia ratio” or “admission glucose delta”/“glycemic gap”. This definition may serve to start a consensus document of the experts in the field. The evidence accumulates supporting the possibility to recognize stress hyperglycemia also in AMI patients with diabetes mellitus (DM) by calculating glycemia during the previous 2-3 months using glycated hemoglobin. Moreover, it is now obvious that 2007 definition of stress hyperglycemia did not take into account the necessity to separate cut-offs for the subgroups with vs. without DM. Conclusions. We demonstrated the insufficiency of the current 2007 definition of stress hyperglycemia, provided evidence-based recommendation for the improvement and suggested the need for a consensus of the experts on this topic. In order to optimize the treatment of stress hyperglycemia in numerous critical illnesses, we ought to have its universal definition (as we already have the universal definition of AMI).

Obesity involves both genetic and environmentl influences, but the mechanisms of the genetic effects are not well understood.\r\nObjective. The aims of the study were to investigate the frequency of perilipin gene polymorphism in order to identify the relationship between insulin resistance and gene polymorphism in obese women.\r\nSubjects and methods. Study population included 31 obese women and 10 women with normal weight as a control group. All of the entire coding exons of PLIN gene were amplified by polymerase chain reaction (PCR). Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA-IR).\r\nResults. In the obese group, 29 (93.6%) patients were homozygous and 1 patients (3.2%) was heterozygous for the c.580C>.G (p.Pro194A1a)(rs. 6496589) mutation and 1 patient (3.2%) was Pro194A1a. Homozygous. Val156Leu. Heterozygous mutation at exon 5 at PLIN gene (p=0.072). As for exon 8 at PLIN gene in obese group, 6 patients (19.3%) had heterozygous for the c.1113T>C (Pro371Pro) (rs2304796) mutation, and 12 patients (38.7%) had heterozygous for the c.1113T>C and c.1119C>T (p. Val373Val) (rs2304795) mutation, and 4 patients (12.9%) had homozygous for the c.113T>C and c.1119C>T mutatons (p=0.009). In obese patients with no nucleotide substitution at exon 8, mean levels of systolic and diastolic blood pressures were higher than those of obese subjects with gene polymorphism. However, there were no statistically significant differences for HOMA-IR levels between obese women with and without perilipin gene polymorphism.\r\nConclusions: Perilipin gene polymorphisms such as heterozygous and homozygous for the c.1113T>C and c. 1119C>T (rs2304795) at exon 8 were associated with obesity risk. However, no relationship was found between insulin resistance and polymorphisms of perilipin gene in obese women.

Aim. The goal was to study immunostaining with Inhibin alpha, Melan- A and MNF 116 in tumors located in the adrenals (benign adrenocortical tumors and metastatic lesions in the adrenal gland) because sometimes pathology cannot distinguish between the two. Patients and Methods. We included 35 patients with benign adrenal tumors and 15 patients with adrenal metastases from nonadrenal tumors submitted to laparoscopic (n=40) or classical (n=10) surgery. In our study we have explored immunostaining with inhibin α-subunit, melan-A, MNF 116 in adrenocortical tumors and metastatic lesions in the adrenal gland in order to make the distinction between primary adrenal cortical lesions and metastatic lesions. Results. All nonsecreting adrenocortical adenomas were stained with inhibin α-subunit and melan-A, but did not stain with MNF 116. All adrenal metastases stained with MNF 116 but were negative for inhibin α-subunit and melan-A with the exception of the 2 melanomas, which stained for melan-A. Conclusion. Inhibin α-subunit and melan-A were sensitive for benign adrenocortical tumors, while MNF 116 was sensitive for metastases from extraadrenal tumors.

Secretion is a basic process in all cells and is involved in important functions such as the release of hormones from endocrine and neuroendocrine cells, in neurotransmission, the release of digestive enzymes and acid secretion, etc, having an important role in the physiology of many metabolic processes of tissues and organs. Contrary to an accepted belief of more than 60 years that the final step in the process of secretion is the total incorporation of secretory granule membrane into the cell plasma membrane for the delivery of secretory product to the outside of the cell, studies made in the last 25 years demonstrated a completely different molecular mechanism of secretion, this being a highly regulated process. Discovery of a new cellular structure, the “porosome”, in principal with the aid of atomic force microscopy (AFM) and transmission electron microscopy (TEM), and the discovery of SNARE (Soluble NSF Attachment Protein REceptor) and SNAREs-induced membrane fusion, and the regulated expulsion of secretory product via secretory vesicle swelling with Aquaporin 1 (AQ1) and Ca2+ implicated, has finally provided us with an understanding of cell secretion at the molecular level. The current study was undertaken to present this new concept regarding the cellular process of secretion, using original illustration of our researches.