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Background/Aim. Thyroid nodules are usually asymptomatic and may occur in 68% of the general population. In most cases, they are discovered incidentally. As malignancy is proven in 10–15% of cases, a rational diagnostic approach is necessary. The aim of this retrospective study was to examine and grade different characteristics of patients with nodular and multinodular atoxic goiter in order to identify the potential predictors for the assessment of thyroid cancer risk. Methods. The study included 275 patients with nodular and multinodular atoxic goiter hospitalized at the Clinic for Endocrinology of the Military Medical Academy, Belgrade, Serbia, from January 1, 2017, to October 1, 2022, for preoperative preparation. The most relevant clinical, biohumoral, and pathomorphological characteristics were analyzed. Results. Patients with multiple thyroid nodules were older (57.21 ± 13.16 vs. 49.36 ± 15.83 years, p < 0.001) and had higher body mass index (29.12 kg/m2 vs. 26.50 kg/m2, p = 0.004) compared to patients with one nodule. On the other hand, patients with one thyroid nodule had a higher level of the thyroid-stimulating hormone than patients with multiple nodules (1.73 mIU/L vs. 1.21 mIU/L, p < 0.0001). Comparison of patients with and without proven thyroid cancer has shown a highly significant association between the higher categories of Bethesda classification and the presence of cancer (Bethesda IV–VI vs. Bethesda II–III, 52.2% vs. 22.3%, respectively, p = 0.002). Conclusion. Considering all the observed parameters, the cytological finding of fine needle aspiration biopsy emerged as the only one with predictive relevance for assessing thyroid cancer risk.

Background/Aim. Prediabetes is a condition that refers to the state of hyperglycemia not sufficiently high to reach the diagnostic values for type 2 diabetes mellitus (T2DM). This condition often precedes the appearance of T2DM. The association between the development of early glycoregulation disorders and the state of low-grade chronic inflammation is still not sufficiently well understood. The aim of the study was to assess the values of different inflammatory mediators and biomarkers in individuals with prediabetes. Methods. This cross-sectional, observational study included 60 respondents divided into two groups: the prediabetes group (PDG) with 31 patients and the healthy control group (HCG) with 29 respondents. Serum values of seven selected cytokines/biomarkers were compared between the two groups. Examined biomarkers were: interleukin (IL)-1β, IL- 6, IL-8, IL-18, tumor necrosis factor (TNF)-α, E-selectin, and vascular endothelial growth factor (VEGF)-A. In addition, the values of body mass index (BMI), waist circumference (WC), blood pressure (BP), serum triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were also compared between the two groups. Results. PDG patients had statistically significantly higher TNF-α values compared to the H CG patients ( 73 pg/mL vs. 55 pg/mL, p = 0.024). A trend towards higher levels of IL-8 and I L-1β and lower levels of E-selectin, VEGF-A, and IL-18 was registered in PDG patients but without statistical significance. Furthermore, PDG patients had higher values of BMI, WC, systolic BP, serum TG, FPG, and HbA1c when compared to HCG. Conclusion. The results of our study suggest the importance of inflammation and some inflammatory mediators in the pathogenesis of early glycoregulation disorder. We believe that the main goal of future studies should focus on anti-inflammatory therapy in prediabetes.

Background/Aim. Hyperglycaemia has a detrimental effect on the progress of micro/macrovascular complications in patients with diabetes mellitus type 2 (T2DM). Additionally, all known complications in T2DM are coupled with oxidative stress developed from different metabolic pathways. The aim of this study was to estimate the quality of glucoregulation and the degree of oxidative stress in T2DM patients depending on the applied therapeutic protocol and assess their correlation with clinical data and crucial biochemical parameters important for the development of diabetes complications. Methods. All included patients were divided into two groups: those treated with oral antidiabetic drugs (OAD) and those treated with oral antidiabetic drugs and insulin (OA-DINS). Thiobarbituric acid reactive substances (TBARS), total sulfhydryl groups (TSH), the activity of superoxide dismutase (SOD), total nitrites (NOx), vascular endothelial growth factor (VEGF), and activities of matrix metalloproteinase 9 (MMP9) were measured, together with lipid profile and routine biochemical parameters. All subjects were analyzed for demographic characteristics and detailed medical history as well as smoking habits and calculated for body mass index (BMI). Results. All patients were uniformly poor glucoregulated and dyslipidemic. SOD activity was decreased, and lipid peroxidation was increased in the OAD group compared to OADINS. Deficient glucoregulation in both the OAD and the OADINS groups did not associate with an oxidative state outcome. In both of these groups, the concentrations of VEGF and MMP9 were significantly higher than in controls. Conclusion. The better antioxidative outcome, expressed with a normalized concentration of TBARS, preserved TSH, and normalized SOD activity in T2DM patients treated with OADINS compared to those treated exclusively with OAD, suggests the need for more careful consideration of earlier insulin introduction into T2DM therapy in order to prevent the development of complications.

Background/Aim. Incidentalomas of the adrenal gland are adrenal masses commonly discovered by chance on imaging not performed for suspected adrenal disease. The aim o f t his study was to analyze clinical, hormonal and histopathological characteristics of adrenal incidentalomas. Methods. This retrospective study included 85 patients (32 men and 53 women) examined for adrenal incidentalomas at the Clinic for Endocrinology, Military Medical Academy in Belgrade, from January 2013 to December 2017. The age of the patients, gender, size, and localization of adrenal tumors, functional activity, as well as the presence of comorbidities were analyzed. Adrenalectomy was performed in 35 patients due to its size and functional activity, and histological findings were analyzed. Results. The largest number (56.4%) of the adrenal tumors, was detected by ultrasound examination of the abdomen, 23 (27.2%) by abdominal computed tomography (CT) scan, 13 (15.2%) by chest CT scan and 1 (1.2%) by magnetic resonance (MR) imaging of the abdomen. The average tumor size was 3.8 ± 2.3 cm (range from 1 to 1 5 c m). Adrenal tumors were bilateral in 20 (23%) patients, in 39 (46%) patients, the tumors were localized in the right adrenal gland, and in 26 (31%) in the left gland. Subclinical hypercortisolism, defined as insufficient cortisol suppression during overnight dexamethasone test (1 mg), was observed in 34 (40%) patients, while the absence of cortisol suppression (autonomous cortisol secretion) was found in 4 (4.7%) patients. In the remaining 47 (55.3%) patients, complete overnight suppression of cortisol secretion was achieved. Thirty-five (41%) patients underwent adrenalectomy; among them, in 4 (11.4%) cases, adrenocortical carcinoma was found, 15 (42.9%) were adenomas, pheochromocytoma was found in 4 (11.4%) cases, nodular hyperplasia in 5 (14.3%) cases, distant metastasis in one (2.8%) case and the remaining were different benign masses. Conclusion. For patients with adrenal incidentalomas, two fundamental questions on determining the functionality of the tumor and/or the presence of malignancy need to be clarified. All patients with adrenal incidentaloma should undergo hormonal evaluation for autonomous or possible autonomous cortisol secretion, as well as for autonomous, adrenergic, and mineralocorticoid excess. In patients with autonomous adrenal secretion, surgery is indicated even if the typical clinical manifestation is absent.

Background/Aim. Prolonged hyperinsulinemia accelerates the process of endothelial dysfunction and arteriosclerotic changes affecting the development of cardiovascular and cerebrovascular diseases. There are various measuring techniques for the evaluation of early functional changes in the arterial wall such as: flow-mediated endothelium-dependent vasodilation, impulse wave analysis, intima-media thickness assessment, venous plethysmography and so on; however, each has certain limitations in results interpretation. The aim of this study was to indicate the association of the pulsatility index (PI) that shows peripheral arterial contractility, with the changes in metabolic parameters under insulin resistance conditions. Methods. The study included a total of 30 healthy obese subjects with the values of body mass index more than 30 kg/m2, randomized with double blind design into two groups: placebo and orlistat. The extent of insulin sensitivity was calculated on the basis of glycemia and insulinemia values using an appropriate formula. Results. The obtained results suggest a statistically significant improvement in the PI index in the orlistat group (p < 0.002), while there was no such improvement in the placebo group. Conclusion. The results obtained in this study indicate the improvement in insulin sensitivity within early arteriosclerosis is a significantly favorable effect of orlistat on peripheral arterial circulation additionally supported by the reduction in levels of lipid fractions, especially triglycerides. Early hemodynamic changes under conditions of the reduced insulin resistance are characterized by the increase in arterial wall contractility evaluated by the PI determination.

Background/Aim. Vitamin D insufficiency/deficiency is often present in patients with type-2 diabetes mellitus (DM) and could present a risk factor for rapid progression of diabetic nephropathy and for higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on proteinuria, cholesterol, triglycerides, C-reactive protein (CRP) and hemoglobin A1c in patients with type-2 DM and vitamin D insufficiency/ deficiency. Methods. This prospective, cohort study included 90 patients with type-2 DM and vitamin D insufficiency/ deficiency divided into 3 equal groups: with normal proteinura, with microproteinuria and with macroproteinuria. Therapy included six months of supplementation with cholecalciferol drops: first two months with 20,000 IU twice weekly, than if level of vitamin D was below normal the same dose was given next four months. If the level of vitamin D was normal 5,000 IU was given twice weekly. At the begining and at the end of the study the levels of urea, creatinine, fasting blood glucose, calcium, phosphorus, cholesterol, triglycerides, CRP, hemoglobin A1c, intact parathyroid hormone, 24-hour urine protein and creatinine clearance were determined. Levels of calcium, phosphorus and vitamin D were also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results. The lowest level of vitamin D before therapy was found in patients with macroproteinuria, while at the end of the study the significantly higher level of vitamin D was found in all three groups. After 6 months of therapy a significant decrease of 24-hour urine protein, cholesterol, triglycerides, hemoglobin A1c in all three groups, and CRP in patients with normal proteinuria and microproteinuria were found. Significantly negative correlation between vitamin D and 24-hour urine protein, cholesterol and CRP was found in patients with macroproteinuria. Also, significantly negative correlation was found between vitamin D and hemoglobin A1c, in patients with normal proteinuria, vitamin D and CRP in patients with microproteinuria. Conclusion. A preventive use of high-dose cholecalciferol supplementation in patients with type-2 DM (with or without proteinuria) decreases cholesterol, triglycerides, proteinuria, CRP and hemoglobin A1c.

Introduction. Hypokalemic thyrotoxic paralysis is a very rare form of periodic paralysis in Caucasian population. In this population, a more frequent form is familiar hypokalemic periodic paralysis with the same clinical presentation. It is flaccid paralysis of proximal muscles in extremities. Having in mind that clinical presentation of hyperthyroidism in these patients is milder than it could be expected with given values of thyroid hormones, differential diagnosis to other forms of hypokalemic paralysis is essential. Case report. We presented a case of a young male with hyperthyroidism and severe periodic flaccid paralysis particularly of leg muscles. Laboratory findings showed elevated thyroid hormones levels and hypokalemia during the attacks with normalized potassium levels between attacks. The patient had no relatives with the similar condition. Also, he never had anything like these attacks prior to development of hyperthyroidism. After differential diagnosis, other reasons for hypokalemic periodic paralysis were excluded. We intensified the hyperthyroidism treatment and resolved hypokalemic periodic paralysis attacks with potassium chloride (KCl) infusions. The patient was advised to start a definitive treatment of hyperthyroidism after stabilization of hormonal levels. Conclusion. Hypokalemic thyrotoxic paralysis is a rare and potentially dangerous condition which, if recognized, can be prevented by resolving hyperthyroxinemia and the use of nonselective β blockers.

Background/Aim. Inflammation is the most important factor in the genesis of vascular complication in the endstage renal disease. The serum C-reactive protein (CRP) level is a sensitive marker of systemic inflammation as well as a predisposing factor for cardiovascular and all cause mortality in patients on hemodialysis. Albumin is the negative acute phase protein and its synthesis declines during the inflammation. The patients undergoing hemodialysis have a high prevalence of protein-energy malnutrition, due to reduced protein synthesis and increased degradation. The low serum albumin levels in these patients originate from the complex setting of conditions with systemic inflammatory response as a major cause, malnutrition and overhydratation. The aim of this study was to determine the prevalence of elevated CRP levels in the dialysis patients and to analyse its correlation with serum albumin levels and other parameters of nutritional status. Methods. The study included 49 patients on maintenance hemodialysis at the Department of Hemodialysis, Clinic of Nephrology, Military Medical Academy, Belgrade, Serbia. In order to analyse the parameters, the blood samples were taken during the arteriovenous fistula (AVF) puncture and before the second weekly dialyse. The following parameters were determined: serum levels of urea and creatinine before and after the dialysis procedure, CRP, hemoglobin, fasting glycemia, total cholesterol, triglycerides, albumins, iron, glycosylated hemoglobin (HbA1c), fasting insulinemia and C-peptide only before the dialysis. Results. Out of 49 patients on maintenance hemodialysis, 37 (75.5%) were males and 12 (24.5%) females with the average age of 56.04 ± 13.93 years. The average duration of the dialysis treatment was 7.37 ± 5 years. The high serum CRP levels (more than 3 mg/L) was found in 65.3% of patients. Singificantly more diabetic patients were observed in the group with the higher CRP levels (n = 12) compared to the group with the normal CRP levels (n = 3) (p ≤ 0.05). A significant positive correlation was found between the CRP value and urea values after the dialysis procedure. We found negative correlation between the CRP values and serum albumin, HbA1c, total cholesterol and triglyceride levels, with no statistical significance. Conclusion. Our study observed a high rate of inflammation in the dialysis patients presenting as high frequency of the elevated CRP levels in the examined group. Negative correlation between CRP levels and serum albumin as well as with some other parameters of nutritional status, suggests that chronic inflammation may be the missing link that actually connect protein energy malnutrition with high morbiditiy and mortality rate in these patients.

Background/Aim. The neuropathic pain (NP) treatment is a big medical and socioeconomical problem. The new sorts of the NP treatment was developed and are applied in case of a medical treatment failure. The aim of this work was to investigate the efficacy of the ultrasound-assisted treatment of the resistant and chronic peripheral neuropathic pain with the local anesthetic nerve blocks. Due to the inefficacy of conventional treatment, three local anesthetics (shortacting, medium-term and long-acting) were administered in a series of the same minimal dose on a daily basis. Complications, side effects, the execution time of procedure and the onset time of local anesthetic were also investigated. Methods. In this prospective, randomized and doubleblinded study, 108 patients (of which 53 were diagnosed with diabetes and 55 with radiculopathy) with the resistant and chronic peripheral neuropathic pain in the lower extremities were treated with a series of ultra-sound assisted peripheral nerve blocks. The conventional treatment was exhausted. The presence of this neuropathic pain was confirmed by, at least, one of the three scales – the Leeds Assesment of Neuropathic Simptoms and Signs (LANSS) scale, the Dolour Neuropathic 4 questions (DN4) scale and the pain DETECT(PD-Q) scale. Other therapies were not applied. The nerve blocks were administered on a daily basis until the relief of pain (visual analogue scale – VAS < 30), and after that, two additional nerve blocks were given. The three local anesthetics of the different duration of therapeutic effect were given at the same minimal dose: the schortacting (1% procaine-chloride solution), medium-term (1% lidocaine-chloride solution) and long-acting (0.25% levobupivacaine-chloride solution) local anesthetics were used. The therapeutic efficacy was measured with the percentage reduction in the pain intensity on the VAS scale before and after the therapy and one month after the treatment: > 50% – excellent results; 31–49% – good results; < 30% the therapy did not work. The side effects, complications, the execution duration of procedure, the onset time of numbness, the number of corrections of the needle direction were recorded as well. Results. For all three groups: nerve blocks took 5.4 ± 1.48 minutes to do (withouth difference among the groups), the onset of numbness occured, on average, within 3.75 ± 2.62 minutes (withouth differences among the groups), and the need for corrections of needle direction was minimal (1.03 ± 0.17 corrections). All the patients experienced a loss of pain sensation (VAS < 30); when a long-acting anesthetic was used, the number of required nerve blocks was significant (p < 0.001) smallest (4.33 ± 0.63 blocks), than in other two groups, and the percentage pain reduction was highest (73.13%) (p < 0.001). The pain relief lasted one month after the therapy without the application of any other therapy. Neither complications nor side effects were observed. Conclusion. The procedure dercibed is a safe, efficient and easy-to-perform and does not lead to any complications and side effects. The pain relief is achieved most effectively and rapidly with the longacting local anesthetics, and maintained even for one month without the introduction of any additional therapy.

Background/Aim. Diabetic neuropathy (DN) is the basic complication of diabetes, associated with impared glucoregulation, metabolic distrurbances, microvascular vessel damage and increased cardiovascular risk. We monitored the impact of glucoregulation on the efficacy of painful diabetic neuropathy (PDN) treatment, when all pharmaceutical treatment options were exhausted. Methods. Patients (n = 53, both gender, average age 68.3 ± 12.6) with PDN resistant to the pharmacotherapy were treated with the ultrasound- guided local anesthetic (0.5% procaine hydrochloride, 1% lidocaine, 0.25% levobupivacaine) blocks. Neuropathy was confirmed in accordance with the applicable European Federation of Neurological Societies (EFNS) criteria. Glycosylated hemoglobin (HbA1C) and blood glucose levels were monitored before and after therapy and one month after the treatment. Neuropathic pain was confirmed by Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) or Douleur neuropathique (DN4) or pain DETECT scales. The pain intensity was assessed by Visual analog scale, Neuropathic pain symptom and Neuropathic pain symptom inventory (VAS, NPS and NPSI, respectively) scales before and after therapy and one month after the treatment. The efficacy of the therapy was assessed as: excellent result (> 50% of pain loss), good result (30%–49% of pain loss and the therapy does not work (< 30% of pain loss). The correlation between glucoregulation and the outcome was examined. Results. Because the values of glycenia and HbA1c were not different among patients treated with different local anesthetics, they were presented together. All patients had elevated blood glucose and HbA1C levels before (8.23 ± 2.77 mmol/L and 8.53% ± 2.48% respectively), after (8.43 ± 2.461 mmol/L and 8.85% ± 2.87%, respectively) and one month after the treatment (8.49 ± 2.22 mmol/L and 8.51% ± 2.09%, respectively). The loss of the pain was not result of the decrease in blood glucose and HbA1C blood levels. VAS, NPS, NPSI values were the following before the therapy: 81.53 ± 11.62 mm; 62.00 ± 13.04; 53.40 ± 17.63, respectively; after the therapy: 29.00 ± 9.23 mm; 13.79 ± 6.65; 11.83 ± 7.93, respectively; and one month later: 26.15 ± 8.41 mm; 12.68 ± 6.03; 9.81 ± 7.64, respectively]. There was no correlation between glucoregulation and excellent outcome. Conclusion. Even though the disturbance of glucose control is the key factor for the progression of PDN, it is not significant for the outcome of the pain treatment. New investigations are required.

Introduction. Polycystic kidney disease is a hereditary kidney disease characterized by the occurrence of cysts (fluid-filled enlargements) in cortex or medula of the kidney, and is inherited in an autosomal dominant or autosomal recessive manner. In addition to multiple cysts in kidneys, there may be many extra-renal manifestations (cysts of the liver, pancreas, lungs, heart, etc.), among which the most serious one is intracranial aneurysms. Case report. A 57-year-old female patient with polycystic kidney disease and stage IV renal failure was hospitalized at our clinic due to decreased renal function, the development of urinary tract infections, headaches and unregulated blood pressure despite the usual treatment. This patient also had a number of associated diseases: obesity, diabetes mellitus (the insulindependent type), hypothyroidism, and depression syndrome. After better regulation of blood pressure, resolved urinary tract infections and improved renal function, there were still persistent headaches (resulting in the excessive use of analgesics). With adequate preparation, multislice computed tomography (MSCT) angiography of blood vessels of the head was performed. As a result, we diagnosed the saccular intracranial aneurysm (IA) with anterior localization. Regarding the symptoms, age and comorbidity, digital subtraction angiography (DSA) was performed, and showed saccular IA (5.2 mm × 4 mm), with wide neck affecting both middle cerebral artery branches (MCA). During the procedure the stent was placed, which filled the aneurysm with spirals, cutting it off from circulation. After the successful procedure and without further complications, the patient no longer had headaches and blood pressure was maintained within the required limits with stable parameters of chronic renal failure. Conclusion. The case of the patient with polycystic kidney disease, stage IV chronic renal failure, with a number of comorbidities (headache, obesity, hypertension, diabetes mellitus, hypothyroidism) and diagnosed with symptomatic intracranial aneurysm was successfully solved with a multidisciplinary approach, emphasizing the importance of teamwork in daily practice.

Background/Aim. Arterial stimulation with calcium and venous sampling (ASVS) enables us to reach the goal of avoiding that any patient with insulinoma undergoes a blind surgical exploration. Since ASVS is both a functional and morphological localization procedure, its sensitivity is not influenced by factors that are causing the insensitivity of usual anatomical and morphological procedures. Based on our own experience in preoperative localization of insulinoma, we indented to show why we believe that ASVS should be performed to all patients regardless of data collected from other preoperative localization methods. Methods. We have analyzed the accuracy of preoperative localization methods retrospectively. First anatomical and morphological procedures like transabdominal ultrasound (US), endoscopic ultrasound (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) were done. Then we analyzed the data collected during a functional procedure which, at the same time, allows regionalization (ASVS). To estimate the accuracy, the results of every single method were correlated with the operative findings in all sixteen cases. Results. Prior to ASVS, fourteen patients underwent US, fifteen had CT, MRI was performed in eight patients and EUS in thirteen. Using only one of these methods enabled identification of tumors in five patients, using two methods in six patients while three and four in one patient each. For three patients, none of these methods was successful. ASVS revealed that all seen tumors were functional except three of the six visualized with two methods (US and EUS). In two of these three cases, US and EUS localized the tumors in pancreatic tail/body while ASVS accurately identified the tumors in pancreatic head. For these patients US and EUS showed false positive results. In the third of these patients EUS showed the tumor localized in pancreatic head, while US and ASVS accurately pointed to tail. This, too, was a false positive result of EUS. ASVS successfully provided regionalization data in three patients where other visualization methods failed. Operative and later histological findings confirmed the accuracy of ASVS in all sixteen patients including two patients that previously underwent distal pancreatectomy based on false positive EUS findings. Conclusion. Two patients, with accurate insulinoma regionalization in pancreatic head, obtained with ASVS, previously underwent unsuccessful distal pancreatectomy based on the false positive EUS findings. The same goes to three other patients with the false positive results obtained with other anatomical and morphological findings, as well as those three patients that had no preoperative visualization with other methods prior to ASVS. Therefore we suggest ASVS performing in each suspected insulinoma patient before the surgery, regardless of the data collected using other methods. This would enable us to test functional characteristics of visualized findings and to regionalize part of pancreas with uncontrolled insulin secretion when no suspicious changes were found.

Introduction. Fahr´s syndrome is a rare, slowly progressive, neurodegenerative disorder, characterised by extensive, bilateral, and symmetrical basal ganglia calcification. It is associated with neuropsychiatric manifestations and gradually progressive cognitive impairment. Fahr's syndrome is the secondary form of brain calcification that is caused by various metabolic, infectious, or degenerative diseases. Case report. We presented a middle-aged male with Fahr's syndrome due to primary idiopathic hypoparathyroidism. Clinical diagnosis was based on signs and symptoms of hypocalcemia, progressive neuropsychiatric illnesses, laboratory evidence of hypoparathyroidism, and radiological signs of calcifications in the basal ganglia. The patient improved after only a few days of intravenous rehydration and calcium substitution, followed by oral supplemental calcitriol. Conclusion. Timely recognition of idiopathic and iatrogenic hypoparathyroidism allows appropriate treatment that can prevent the development and clinical manifestations of Fahr´s syndrome and potentially slow its progression.

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Introduction. Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. Case report. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Conclusion. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

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Introduction. Paraganglioma is a rare neuroendocrine neoplasm that may arise from the extra-adrenal autonomic paraganglia. Urinary bladder paraganglioma is typically presented as repeated episodes of palpitations, headache or blood pressure rise immediately after micturition. Management of these tumors includes radical surgical treatment with preoperative antihypertensive preparation, and a life-long follow-up. Case report. We presented a middle- age female patient with functional urinary bladder paraganglioma, with a 3-year history of repeated episodes of abdominal pain, dysuria and hematuria. After obtaining more precise anamnestic data, the patient reported occasional simultaneous presence of mild adrenergic symptoms, that did not cause any particular attention at first. Morphological and biohumoral examinations suggested paraganglioma of the urinary bladder. Open partial cystectomy was performed, detecting a submucosal mass, while immunohistochemical analysis confirmed the presence of chromaffin tissue. Clinical manifestations, diagnostic approach, management and histopathological findings of urinary bladder paraganglioma are discussed. Conclusion. Since the prognosis with localized paraganglioma is good, we underlined the importance of a well-timed, accurate and detailed medical history in all the patients with even mild, inexplicable micturition-provoked adrenergic symptomatology.

Background/Aim. Insulinomas are rare benign tumors in the most cases and the most frequent endocrine tumors of the pancreas. A wide spectrum of clinical manifestations in patients with insulinoma is the reason for difficult recognition of the disease with a long period of time between the onset of symptoms and the diagnosis. Diagnostic procedures include Whipple’s triad, 72-hour fast test and topographic assessment. The only currative therapy for patients with insulinoma is operative treatment. Methods. This retrospective study included 42 patients with diagnosis of insulinoma treated in our institution in a 60-year period. In all the patients a demographic and clinical data, types of biochemical methods for diagnosis, and diagnostic procedures for insulinoma localization were analyzed. Tumor size and localization, surgical procedures, postoperative complications and outcome were assessed. Results. A study included 42 patients, 29 women and 13 men. The median age at diagnosis was 43 years. Median time between the onset of symptoms and diagnosis was 3 years. The most common clinical symptoms and signs were disturbance of consciousness and abnormal behavior in 73%, confusion and convulsions in 61% of patients. The diagnosis of insulinoma was estimated by Whipple's triad and 72-hour fast test in 14 patients. Determination of insulinoma localization was assessed by angiography in 16 (36%) of the patients, by ultrasound (US) in 3 of 16 (18.8%) patients, by abdominal computed tomography (CT) in 8 of 18 (44.5%) patients, and magnetic resonance imaging (MRI) in 2 of 8 (25%) patients. Insulinoma was found in 13 of 13 (100%) patients by arterial stimulation with venous sampling (ASVS) and in 13 of 14 (93%) patients by endoscopic ultrasound (EUS). Of the 42 patients, 38 (90.5%) underwent operative procedure. Minimal resection was performed in 28 (73.6%) of the patients [tumor enucleation in 27 (71%) and central pancreatectomy in one (2.6%) of the patients], and the major resection was performed in 9 (23.6%) of the operated patients [distal splenopancreatectomy in 8 (21%) and pancreaticoduodenectomy in one (2.6%) patient]. The overall mortality rate in postoperative period was 2.6% (one patient). Conclusion. A combination of ASVS and EUS as diagnostic procedures ensures high accuracy for preoperative determination of insulinoma localization. Minimal resection such as enucleation shoud be performed whenever it is possible.

Introduction. Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Case report. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Conclusion. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

Background/Aim. According to the current principles, autonomous functional thyroid nodules are treated by surgery or by radioiodin therapy. Ultrasound guided percutaneous ethanol injection into solid tumors of the soft tissues was a starting point in attempts to treat the thyroid nodules by the same method. The aim of the study was to assess the efficiency of percutaneous injection in treating solitary, nontoxic, autonomous thyroid nodules of up to 15 mL volume. Methods. In 25 patients with solitary nontoxic autonomous thyroid nodules diagnosed by tehnetium-99m scanning as an intensive area having a complete supremacy in the paranodal tissue, an ultrasound guided percutaneous ethanol injection was applied. The procedure was carried out repeatedly once a week until the reduction in nodule size to 50% of the initial size was achieved. Results. An average size of the nodule before curing was 9.68 ± 5.01 mL. An average quantity of the injected ethanol was 9.52 ± 5.08 mL, ie 1.06 ± 0.48 mL/mg of the tissue. The regression of the nodule size in the successfully (Δvol% u = - 57.09 ± 13.75%, p < 0.001) and partly successfully cured (Δvol du = -48.45 ± 14.35%, p < 0.05) was statistically significant compared to the size before the treatment. After ceasing ethanol injection, 18 months later, a further size regression (Δvol% = -79.20 ± 9.89%) compared to the initial one (p < 0.001) was noticed. Soon, after the procedure was finished, a statistically significant concentration increase of Thyroid Stimulating Hormone (TSH) was noticed compared to the initial values (0.18 ± 0.16 vs 0.34 ± 0.31 mU/L, p < 0.01). According to the given criteria, in two female patients satisfactory results were not achieved, but, a year later, in one of them the nodule was not seen by repeated scintigram. The number and frequency of side effects were insignificant. Conclusion. Repeated percutaneous ethanol injections into nontoxic solitary autonomous thyroid nodules result in disappearing of authonomy. The regression of the nodule size of more than 50% compared to its initial volume, as well as the increase in concentration of TSH for more than 50% are the signs of a successful treatment.

Background/Aim. Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. Method. The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA(16%), AC(15%) and CC(11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. Results. After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95%CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 ± 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 ± 0.03 (p = 0.052), and in the CC genotype by 0.01 ± 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 ± 24 mmHg at baseline, to an average of 121 ± 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 ± 10 mmHg at baseline to 115 ± 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 ± 13 mmHg at baseline to 78 ± 8 mmHg (p = 0.004), and in the AC genotype from 88 ± 5 mmHg at baseline to 11.7 ± 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). Conclusion. The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Aim. To determine the efficacy of AT1 receptor antagonist (valsartan) in decreasing of urinary excretion of albumin in normotensive patients with type 1 diabetes and incipient diabetic nephropathy (DN). Methods. This was a prospective, randomised, placebo-controlled study, which included 20 patients with insulin-dependent diabetes mellitus, mean age 25.15, and the duration of diabetes of 13.95 years. All the patients were normotensive, with persistent microalbuminuria (incipient phase of DN). Patients were randomly divided into two groups (10 patients each): valsartan group treated with 80 mg valsartan daily during 6 months, and the group treated with placebo during the same period. Both groups were similar and comparable concerning the observed parameters at the beginning of the study. Results. After 6 months therapy, valsartan caused significant decrease of urinary albumin excretion rate (UEAR) by 69.1% from 64.8 to 21.1 mg/24 h, while in placebo group there was an insignificant increase of UEAR by 29.8%. During the follow-up of UEA in the observed groups, at the beginning and the end of the mentioned period highly significant decrease of albumine secretion (p

Introduction. Hemorrhagic fever with renal syndrome (HFRS) is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS.

Introduction. Hemorrhagic fever with renal syndrome (HFRS) is acute infective multisystemic disease followed by febrility, hemorrhages and acute renal insufficiency. Bleeding in the anterior pituitary lobe leading to tissue necrosis occurs in acute stage of severe clinical forms of HFRS, while atrophy of the anterior pituitary lobe with diminution of the gland function occurs after recovery stage. Case report. We presented a patient with the development of chronic renal insufficiency and hypopituitarism as complication that had been diagnosed six years after Hantavirus infection. Magnetic resonance of the pituitary gland revealed atrophy and empty sella turcica. Conclusion. Regarding frequency of this viral infection and its endemic character in some parts of our country partial and/or complete loss of pituitary function should be considered during the late stage of HFRS. [ABSTRACT FROM AUTHOR]

Background/aim: According to the current principles, autonomous functional thyroid nodules are treated by surgery or by radioiodin therapy. Ultrasound guided percutaneous ethanol injection into solid tumors of the soft tissues was a starting point in attempts to treat the thyroid nodules by the same method. The aim of the study was to assess the efficiency of percutaneous injection in treating solitary, nontoxic, autonomous thyroid nodules of up to 15 mL volume., Methods: In 25 patients with solitary nontoxic autonomous thyroid nodules diagnosed by tehnetium-99m scanning as an intensive area having a complete supremacy in the paranodal tissue, an ultrasound guided percutaneous ethanol injection was applied. The procedure was carried out repeatedly once a week until the reduction in nodule size to 50% of the initial size was achieved., Results: An average size of the nodule before curing was 9.68 +/- 5.01 mL. An average quantity of the injected ethanol was 9.52 +/- 5.08 mL, ie 1.06 +/- 0.48 mL/mg of the tissue. The regression of the nodule size in the successfully (deltavol% u -57.09 +/- 13.75%, p < 0.001) and partly successfully cured (deltavol du = -48.45 +/- 14.35%, p < 0.05) was statistically significant compared to the size before the treatment. After ceasing ethanol injection, 18 months later, a further size regression (deltavol% = -79.20 +/- 9.89%) compared to the initial one (p < 0.001) was noticed. Soon, after the procedure was finished, a statistically significant concentration increase of Thyroid Stimulating Hormone (TSH) was noticed compared to the initial values (0.18 +/- 0.16 vs 0.34 +/- 0.31 mU/L, p < 0.01). According to the given criteria, in two female patients satisfactory results were not achieved, but, a year later, in one of them the nodule was not seen by repeated scintigram. The number and frequency of side effects were insignificant., Conclusion: Repeated percutaneous ethanol injections into nontoxic solitary autonomous thyroid nodules result in disappearing of authonomy. The regression of the nodule size of more than 50% compared to its initial volume, as well as the increase in concentration of TSH for more than 50% are the signs of a successful treatment.

Introduction: Our study was aimed at determining whether the polymorphism of genes for different components of the renin-angiotensin-aldosterone system could influence the renal hemodynamic response to losartan treatment., Material and Method: The study included 35 patients with type I diabetes mellitus and persistent albuminuria, genotyped for the 1166 A/C polymorphism gene for the angiotensin II type 1 receptor and I/D polymorphism of the angiotensin-converting enzyme gene. The participants were divided into groups according to the combinations of A or C allele: AA, AC, CC; and according to the combinations of I or D allele: II, ID and DD genotype. The patients received losartan therapy for 12 weeks. The renal hemodynamic measurements were determined at baseline and after the examination period., Results: Losartan therapy significantly reduced the filtration fraction from the baseline by 0.018 +/- 0.024 (p = 0.012) only in the AC genotype. The glomerular filtration rate remained unchanged in all genotype groups. A significant increase in the effective renal plasma flow was obtained only in AC genotype (544 +/- 88 vs 575 +/- 90 ml/min; p = 0.02), while significant reductions in the renal vascular resistance were found in AA group (115 +/- 25 vs 95 +/- 21 mmHg x l(-1) x min(-1), p = 0.001) and in AC group (118 +/- 30 vs 101 +/- 28 mmHg x l(-1) x min(-1); p = 0.001). A significant reduction of the glomerular filtration rate by 8 +/- 10 ml/min was obtained only in the DD genotype (p = 0.016), and only the DD genotype achieved a significant reduction of the filtration fraction by 0.019 +/- 0,022 (p = 0.008). The most pronounced increase of the effective renal plasma flow was found only in the ID genotype (536 +/- 75 vs 591 +/- 63 ml/min; p = 0.01). The reduction of the renal vascular resistance was independent of ACE gene polymorphism., Conclusion: Our study shows that individual renal vascular response to losartan treatment in diabetic patients with persistent albuminuria, could be influenced by genetic polymorphisms.