OBJECTIVE:The aim of this retrospective study is to analyze the outcome and survival of patients with well-differentiated metastatic neuroendocrine neoplasm (NEN) treated with peptide receptor radionuclide therapy (PRRT). SUBJECTS AND METHODS:The treatment was applied to 32 subjects, 18 men and 14 women, aged 39-79 years (median 65 years). The dominant grade of the tumor according to the Ki-67 index was G2 (75%) compared to G1 (25%). The average number of three-day protocol PRRT cycles was 4 (1.00-9.00). Lutetium-177- DOTA0,Tyr3,Thr8-octreotide (177Lu-DOTA-TATE) was used in 22 (69%), both 177Lu-DOTA-TATE and yttrium-90-DOTA0,Tyr3-octreotide (90Y-DOTA-TOC) in 8 (25%), and 90Y-DOTA-TOC in 2 (6%) patients. No adverse effects of PRRT were recorded excerpt one patient who has died soon after the first therapy due to ileus after surgery. RESULTS:Response to PRRT according to response evaluation criteria in solid tumors (RECIST) 1.1. criteria showed that 9 (28%) patients had disease progression, 16 (50%) had stable disease, and 7 (22%) had partial remission. Significantly shorter time until progression or death of 18 months was detected for patients with disease progression than for other groups with stable disease (34.5 months, P<0.02) and partial remission (35 months, P<0.05). However, the values obtained for overall survival were not significantly different between the studied groups being 33 months in subjects with disease progression, and 34.5 and 35 months in groups with stable disease and partial remission, respectively. In 6 subjects, an asymptomatic low hemoglobin level was detected that did not require intervention (Grade1). In 2 subjects, nephrotoxicity occurred with glomerular filtration rate (GFR) values below 30mL/min/1.73m2 (Grade3). CONCLUSION:It can be concluded that PRRT according to a three-day nephroprotection protocol is a reliable and safe method of treatment for advanced NEN. Longer time to disease progression and overall survival in most patients underline the great potential of this treatment method in patients with advanced NEN.

Polycystic ovary syndrome, commonly abbreviated as PCOS, as the most common endocrine disorder in women of reproductive age, is a multifaceted disease characterized by various hormonal imbalances and a great degree of variation in its clinical presentation. This, coupled with its etiology and pathogenesis being incompletely understood, results in a broad disease spectrum that is challenging to accurately diagnose and manage. The primary clinical features which PCOS commonly manifests with include hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, though all three are not necessarily present in all PCOS patients. Hyperandrogenism, manifesting as hirsutism, acne, and male-pattern alopecia, significantly affects both the physical and psychological wellbeing of these patients. Ovulatory dysfunction, presenting as irregular menstrual cycles due to oligo/anovulation, is an important element of PCOS's clinical presentation and leads to the infertility that some of these patients' experience. PCOS is commonly associated with insulin resistance and consequent hyperinsulinemia and metabolic disorders, seen in these patients. Subsequently, women affected with PCOS are at a greater risk of obesity, dyslipidemia, diabetes, and cardiovascular diseases, particularly later in life. The rate of mood disorders, namely depression and anxiety, is also increased in this population. The complex nature of this syndrome makes difficulties in patient care, and its chronic nature emphasizes a proactive stance when it comes to treatment, but also a careful assessment of all the elements of the disease.

Introduction: Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a inflammatory syndrome, manifested by pain, voiding symptoms, sexual dysfunction, and mental health issues including anxiety. Beneficial effects of exercise are known, but its influence on CP/CPPS has not been investigated. This study aimed to determine the effects of chronic aerobic physical activity on anxiety-related behavior and pain in rats with experimental CP/CPPS. Material and Methods: Adult male Wistar albino rats (n=32) were randomly assigned to 4 groups (n=8 in each): Sham-SED (30-days sedentary-SED protocol on treadmill and intraprostatic injection of 0.9% NaCl); Sham-PA (30-days physically active-PA protocol on treadmill and intraprostatic injection of 0.9% NaCl); CP/CPPS-SED (30-days SED protocol on treadmill and intraprostatic injection of 3% l-carrageenan); CP/CPPSPA (30-days PA protocol on treadmill and intraprostatic injection of 3% l-carrageenan). To establish pain dynamics, scrotal skin pain thresholds were measured by electronic von Frey aesthesiometer (evF) preoperatively: 2 and 1 day, and also postoperatively: 2nd, 3rd, and 7th day. Anxiety-like behavior was estimated by subjectiong the animals to the open field (OF), elevated plus maze (EPM) and light/dark (L/D) tests at the same postoperative days as evF. Results: Rats that developed experimental CP/CPPS showed decreased mechanical pain threshold in the scrotal skin in all postoperative time points, in comparison to the Sham group. Also, in rats with prostatitis increased anxiety-like behavior was observed in OF, EMP and L/D test, compared to corresponding controls. Protocol of 30-day long exercise in rats with CP/CPPS led to reversion of anxiety-like behavior and increased scrotal pain threshold. Conclusion: Results of the present study showed that exercise pretreatment on the treadmill for 30 consecutive days led to the amelioration of anxiety-related and pain-related behavior in rats with CP/CPPS.

Neuroendocrine tumors (NETs) are relatively rare and heterogeneous with a variaty of clinical expression. They derive from the sensory and secretory neuroendocrine cells mainly within the pulmonary and gastrointestinal tract. They comprise less than 2% of all malignancies. On the basis of clinical behavior, histology, and proliferation rate, they are devided into well differentiated (low grade to intermediate grade) and poorly differentiated (high grade) neuroendocrine carcinoma. Tumor stage and grade have the impact on treatment and prognosis. The treatment of choice is surgery. More than 50% of the patients present metastatic disease at the time of diagnosis, thus the systemic treatment should be considered including somatostatin analogs, chemotherapy, targeted therapy, immunotherapy and peptide receptor radionuclide therapy (PRRT). For the diagnosis and follow-up of these tumors, various radiological methods are used (computed tomography, magnetic resonance imaging, ultrasound) as well as endoscopy. Nuclear medicine methods are used in order to exploit their unique properties mainly amine precursor uptake and decarboxylation system characteristics, as well as the expression of somatostatin receptors. These methods enable whole body examination, staging, selection of patient for PRRT and treatment monitoring as well. Imaging can be performed with gamma camera (SPECT, SPECT/CT) or positron emission tomography (PET/ CT). Radiopharmaceuticals used for imaging with gamma camera are usually 99mTc-(V)-DMSA, 99mTcMIBI, 99mTc-HYNIC TOC, 111In-pentetreotide and 131I-MIBG/123I-MIBG. Positron emitting radiopharmaceuticals has superior spatial resolution and faster imaging, such as 68Ga-DOTA-somatostatin analogues, 18F-FDG (particularly for high-grade tumors), 18F-L-DOPA/11C-L-DOPA and 11C-5-hydroxytryptophan that have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory. In this mini-review, the most frequent methods and radiopharmaceuticals are presented, as well as potential development.

Neuroendocrine tumors (NETs) are relatively rare and heterogeneous with a variaty of clinical expression. They derive from the sensory and secretory neuroendocrine cells mainly within the pulmonary and gastrointestinal tract. They comprise less than 2% of all malignancies. On the basis of clinical behavior, histology, and proliferation rate, they are devided into well differentiated (low grade to intermediate grade) and poorly differentiated (high grade) neuroendocrine carcinoma. Tumor stage and grade have the impact on treatment and prognosis. The treatment of choice is surgery. More than 50% of the patients present metastatic disease at the time of diagnosis, thus the systemic treatment should be considered including somatostatin analogs, chemotherapy, targeted therapy, immunotherapy and peptide receptor radionuclide therapy (PRRT). For the diagnosis and follow-up of these tumors, various radiological methods are used (computed tomography, magnetic resonance imaging, ultrasound) as well as endoscopy. Nuclear medicine methods are used in order to exploit their unique properties mainly amine precursor uptake and decarboxylation system characteristics, as well as the expression of somatostatin receptors. These methods enable whole body examination, staging, selection of patient for PRRT and treatment monitoring as well. Imaging can be performed with gamma camera (SPECT, SPECT/CT) or positron emission tomography (PET/ CT). Radiopharmaceuticals used for imaging with gamma camera are usually 99mTc-(V)-DMSA, 99mTc-MIBI, 99mTc-HYNIC TOC, 111In-pentetreotide and 131I-MIBG/123I-MIBG. Positron emitting radiopharmaceuticals has superior spatial resolution and faster imaging, such as 68Ga-DOTA-somatostatin analogues, 18F-FDG (particularly for high-grade tumors), 18F-L-DOPA/11C-L-DOPA and 11C-5-hydroxytryptophan that have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory. In this mini-review, the most frequent methods and radiopharmaceuticals are presented, as well as potential development.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a result of interplay between psychological, immune, neurological and genetic factors, manifested by variety of urological, as well as brain-related symptoms. However, its relation with brain excitability has not been addressed. herefore, our aim was to assess susceptibility to seizures in rats with CP/CPPS. We induced CP/CPPS in adult rats by intraprostatic injection of 3% λ-carrageenan. Sham operated rats served as controls (0.9% NaCl, Sham). On day 7 upon injection, rats were treated with lindane (4 mg/kg) and observed for convulsive behavior (seizure incidence, latency and severity) and EEG manifestations (number and duration of ictal periods). Interleukin levels (IL-1β and IL-6) were measured in prostate, hippocampus, thalamus and cerebral cortex. Scrotal skin mechanical pain thresholds were determined and prostates were histologically evaluated. Animals with CP/CPPS showed significantly higher incidence, decreased latency time and augmented severity of lindane-induced seizures compared with Sham group. EEG revealed increased number of ictal periods in CP/CPPS rats. Higher levels of IL-1β and IL-6 were determined in the thalamus and cortex in CP/CPPS animals vs. Sham. IL-1β level was higher and IL-6 was lower in prostates from CP/CPPS animals comparing to Sham. CP/CPPS development was verified by histological findings of nonbacterial inflammation in the prostates, as well as by significantly decreased scrotal pain threshold in CP/CPPS animals. On the basis of this research, we concluded that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with increased level of IL-1β and IL-6 in the cortex and thalamus.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Introduction: Insulin resistance (IR) is one of the main features of polycystic ovary syndrome (PCOS), and metformin is one of the most commonly prescribed insulin sensitizers in its treatment. Research carried out so far shows heterogeneous results on the effects of metformin on the hormonal and metabolic status of women with PCOS. The aim of the study was to investigate the effect of six-month treatment with metformin (2000 mg per day) on the hormonal and metabolic characteristics of women with PCOS, paired with healthy women by body mass index (BMI) and age. Material and Methods: A number of 20 women with PCOS [age: 23.5 ± 5.9 years, BMI: 24.8 ± 4.2kg / m2] and 20 healthy control group women were tested (age: 24.5 ± 5.3 years, BMI: 23.6 ± 3.0kg / m2). Polycystic ovary syndrome was diagnosed with ESHRE / ASRM criteria. Standard biochemical and hormonal parameters were determined, which were repeated in the PCOS group and after six months of metformin therapy. Insulin resistance was determined using a homeostatic model (HOMA-IR). Results: After six months of metformin therapy in the PCOS group, there was a significant increase in the frequency of menstrual cycle (65% versus 87%, p <0.001), reduction of the degree of hirzutism towards Ferrimann - Galway score (9.5 versus 8.5, p = 0.025), but after the therapy all parameters were still significantly different from the ZK group. After therapy, there was no difference in the concentration of triglycerides between PCOS and ZK (1.3 ± 0.7 versus 0.9 ± 0.4 mmol / L, p = 0.19), which were significantly higher in PCOS compared to ZK before therapy (1.4 ± 0.8 vs 0.9 ± 0.4 mmol / L, p = 0.03). There was no significant effect of BMI therapy, as well as on HOMA-IR and the concentration of androgens that were significantly higher in PCOS compared to ZK, while there was a favorable effect of metformin on the liver. Conclusion: Six-month treatment with metformin, at a dose of 2000 mg per day in women with PCOS, leads to a significant increase in the incidence of menstrual cycle, ovulation and reduction in the degree of hirsutism, as well as a beneficial effect on lipids and liver, and the independent effects of the drug on BMI and IR.

Background: Homocysteine and taurine are non-proteinogenic sulfur-containing amino acids with numerous important physiological roles. Homocysteine and taurine are considered to be neurotransmitters and neuromodulators, the first showing clear hyperexcitability role, while the second is known by its inhibitory and neuroprotective properties. Objective: In this article we addressed the role of homocysteine and its related metabolite homocysteine thiolactone in the development of seizures, focusing on its experimental models in vivo, potential mechanisms of proepileptogenic activity via interactions with glutamatergic neurotransmission, sodium pump activity, oxidative stress, cholinergic system and NO-mediated neuronal signaling, as well as the pharmacological and non-pharmacological approaches to modulate its proconvulsive activity. Additionally, herein we will focus on taurine neuroprotective effects linked with its anticonvulsive properties and mediated by taurine interactions with GABA-ergic and glutamatergic system and oxidative stress.

Gojaznost se danas smatra uzrokom nastanka kardiovaskularne bolesti, tipa 2 dijabetesa, osteoartritisa, maligniteta, ali i faktorom koji doprinosi nastanku reproduktivnih poremećaja i problema plodnosti. Postoji povećan relativni rizik za nastanak anovulatornog infertiliteta u žena sa izraženom gojaznošću i produženo vreme do koncepcije. U žena u reproduktivnom periodu gojaznost je povezana sa povećanim rizikom za nastanak hiperandrogenizma i anovulacije, kao što je slučaj u sindromu policističnih jajnika (PCOS) kao najčešćem hiperandrogenom poremećaju. Postoji veliki broj dokaza u prilog postojanja bliskog odnosa adipokina, gojaznosti, metaboličkog sindroma i reproduktivnih posledica. Redukcija težine za 5-10% dovodi do poboljšanja u kliničkim, metaboličkim i reproduktivnim karakteristikama, kao što je slučaj u žena sa PCOS. Primena insulinskih senzitajzera vodi sniženju hiperinsulinemije, insulinske rezistencije, uspostavljanju normalne menstrualne cikličnosti i ovulacije kod značajnog broja žena sa PCOS. Gojaznost može uticati na stimulaciju ovulacije njenim produžavanjem, povećanjem doze gonadotropina, incidence folikularne asinhronije i prekida stimulacije. Hirurško lečenje gojaznosti predstavlja alternativni vid terapije u slučaju kada ni promena načina života ni farmakoterapijske mere ne daju povoljne rezultate. Za sada ne postoji dovoljno dokaza u prilog preporuke da se barijatrijska hirurgija koristi u lečenju gojaznih žena sa PCOS.

A 45-year old female was admitted to the hospital because of a large adrenal tumor. The history of disease began a year earlier with hypertensive paroxysms accompanied by redness and warmth in the face, profuse sweating, nausea and the urge to vomit. Large abdominal mass in the right adrenal area was detected ultrasonographicaly, and confirmed by CT-scan. Biochemical analyses revealed highly elevated urinary catecholamines (norepinephrine and epinephrine), which led to clinical diagnosis of pheochromocytoma. The patient was operated, and pathohistological finding confirmed the diagnosis. Genetic testing revealed the existence of germline mutation in 46. codone (GTG®GTA,V46V) in succinate-dehydrogenase D gene (SDHD). Pheochromocytoma is a cateholamine-secreting tumor of chromafine cells usually localized in adrenal glands, only 10% are localized in ganglia of simathetic nervous system. The most of these tumors are sporadic, but they can be inherited as a part of four familial cancer syndromes: multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1) and familial pheochromocytoma. These syndromes are caused by mutations in RET protooncogene, VHL tumor-suppressor gene, NF1 tumor-suppressor gene and SDHD gene. In comparison with sporadic, familial pheochromocytomas have different characteristics, and they are usually bilateral. Because of the coexistence of other malignancies, genetic screening of patients with pheochromocytoma is mandatory. These syndromes have autosomal dominant inheritance with high penetrance, and it is important to test first-degree relatives as well as carriers. Genetic screening for mutations in SDHD gene should be done routinely in all patients with apparently sporadic pheochromocytoma.

Polycystic ovary syndrome (PCOS) is the most frequent reproductive disorder in women. PCOS is considered a metabolic disorder closely related to obesity, insulin resistance, hyperinsulinism and unfavourable lipid profile, and all together increases the risk of cardiovascular diseases. The objective of the study was to estimate the concentration of individual lipid fractions in obese PCOS patients as well as to examine the possible connection of changes in lipid fractions regarding the age of the patients. There were 59 obese patients with PCOS examined, who were divided into two groups: < 20 years (group A, n=22) and > 20 years (group B, n=37). The results of these groups were compared with the corresponding from the control groups (groups C and D). Basal values of cholesterol, HDL, LDL, triglycerides, oxidated LDL, Apo AI, Apo AII, Apo V, Apo E and atherogenic indices Apo B/Apo AI and LDL/HDL were analysed. A statistically significant difference between the groups A and V for the total cholesterol (4,20 vs. 5,02 mmol/L), LDL-cholesterol (2,79 vs. 3,42 mmol/L), triglycerides (1,27 vs. 1,50 mmol/L), oxidatedLDL (56,35 vs. 65,17 U/L), Apo V (0,87 vs. 1,03 g/L), Apo B / Apo AI (0,55 vs. 0,68) and LDL / HDL (2,37 vs. 3,06) was determined. It was conformed that in the obese patients with PCOS there was significantly higher level of almost all analysed lipid fractions and atherogenic indices with extremely high oxidation of LDL cholesterol. The PCOS patients have significantly higher atherogenic potential with ageing.

Polycystic ovary syndrome (PCOS) is considered a metabolic disorder closely related to obesity, insulin resistance (IR), hyperinsulinemia and unfavorable lipid profile, all increasing the risk for the occurrence of cardiovascular diseases. The aim of this study was to assess age and body mass index (BMI) related changes of cardiovascular risk factors in 90 women with PCOS. The cut-off age point was 30 years and for BMI 27.8 kg/m2. In all patients systolic and diastolic blood pressure (BP), metabolic parameters comprising values of glucose and insulin during oral glucose tolerance test (OGTT), and basal lipid values were determined. Significant increase in blood pressure (BP) indices, basal insulin values and insulin resistance (IR) assessed by HOMA model were observed with aging and the increase of BMI, while the parameters of glucose metabolism, total cholesterol and triglycerides were significantly elevated only with aging. However, the correlation between the indices of arterial blood pressure, and lipid and glucose metabolism parameters occurred only in patients over 30 years of age, pointing to the causative relation and the consequent deterioration of IR and lipid profile with aging, influencing cardiovascular function in women with PCOS.