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Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012–2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the clinical, biochemical, and sonographic factors influencing the performance of parathormone washout measurement (PTHw) vs. MIBI in the preoperative localization of parathyroid adenoma (PA). The studied group consisted of 39 patients with primary or tertiary hyperparathyroidism. The measurement of PTH concentrations was performed using an electro-chemiluminescence immunoassay. Scintigraphic localization of PA was carried out using dual-tracer planar neck scintigraphy, using 74 MBq 99mTc-pertechnetate and 740 MBq of 99mTc-MIBI. MIBI was unambiguously positive in 74% of patients. Among patients with negative or inconclusive MIBI, 90% had a positive PTHw result. Among patients with negative PTHw, two out of three had a positive MIBI result. The PTHw of lesions <10 mm in their largest diameter yielded positive results in 95%, compared to 75% for MIBI. For lesions ≥10 mm in largest diameter, 88% were visualised using MIBI. In conclusion, PTHw is a highly effective, easy, quick, safe, and relatively cheap procedure which might be considered for PA localisation, especially in patients with lesions presenting typical ultrasound features and a size below 10 mm. MIBI remains a useful procedure in specialized centres, particularly for patients in whom PTHw failed, larger lesions, and in cases of the ectopic location of PA. [ABSTRACT FROM AUTHOR]

Simple Summary: Papillary thyroid cancer (PTC) comprises approximately 80% of all thyroid malignancies. The field of PTC genetics and cancerogenesis remains undetermined. Activated mTOR is involved in the development and progression of PTC. We performed a systematic review of papers studying the expression of the mTOR gene and its relationship with PTC risk and clinical outcome. We also analyzed the data on mTOR protein expression in PTC and reviewed available data on new targeted therapies and the use of mTOR inhibitors in PTC. A systematic literature search was performed using PubMed, Embase, and Scopus databases (the search date was 2012–2022). Studies investigating the expression of mTOR in the peripheral blood or tissue of patients with PTC were deemed eligible for inclusion. Seven of the 286 screened studies met the inclusion criteria for mTOR gene expression and four for mTOR protein expression. Papillary thyroid cancer (PTC) comprises approximately 80% of all thyroid malignancies. Although several etiological factors, such as age, gender, and irradiation, are already known to be involved in the development of PTC, the genetics of cancerogenesis remain undetermined. The mTOR pathway regulates several cellular processes that are critical for tumorigenesis. Activated mTOR is involved in the development and progression of PTC. Therefore, we performed a systematic review of papers studying the expression of the mTOR gene and protein and its relationship with PTC risk and clinical outcome. A systematic literature search was performed using PubMed, Embase, and Scopus databases (the search date was 2012–2022). Studies investigating the expression of mTOR in the peripheral blood or tissue of patients with PTC were deemed eligible for inclusion. Seven of the 286 screened studies met the inclusion criteria for mTOR gene expression and four for mTOR protein expression. We also analyzed the data on mTOR protein expression in PTC. We analyzed the association of mTOR expression with papillary thyroid cancer clinicopathological features, such as the TNM stage, BRAF V600E mutation, sex distribution, lymph node and distant metastases, and survival prognosis. Understanding specific factors involved in PTC tumorigenesis provides opportunities for targeted therapies. We also reviewed the possible new targeted therapies and the use of mTOR inhibitors in PTC. This topic requires further research with novel techniques to translate the achieved results to clinical application. [ABSTRACT FROM AUTHOR]

Background. Ghrelin is a hormone that occurs in acylated (AG) or unacylated (UG) form. Ghrelin strongly stimulates growth hormone (GH) secretion from anterior pituitary, as well as regulates the energy balance and various metabolic parameters. Increased consideration is given to UG, thought to be inactive. Objectives. We aimed to evaluate the levels of total ghrelin, AG and UG in medically naive and treated patients with biochemically active acromegaly, with respect to variables of lipid and glucose metabolism. Material and methods. We studied total ghrelin, AG and calculated UG levels in a group of 24 patients with active acromegaly and 15 healthy controls. Plasma levels of GH, insulin-like growth factor 1 (IGF-1), insulin, glucose, total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and calculated low-density lipoprotein (LDL) cholesterol, triglycerides (TG), apolipoproteins A1 (APO A1), and B-100 (APO B-100) were measured. Results. Patients with acromegaly revealed lower levels of total ghrelin than healthy controls. In pooled data of all subgroups, simple linear regression analysis revealed that total ghrelin concentration was significantly associated with APO A1 concentration (ß = 0.8087; p = 0.0315) and AG concentration was significantly associated with fasting insulin concentration (ß = 15.5183; p = 0.011). There was an inverse association between UG and the patients' age, and positive association between UG and APO A1. Conclusions. Our results suggest that ghrelin may influences metabolic disturbances in acromegaly. It seems that the assessment of AG and UG is superior to total ghrelin measurement. Mechanisms regulating ghrelin acylation and function of each form need elucidation in order to improve diagnostics and treatment of metabolic disturbances, not only acromegaly. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA), a disorder characterized by repetitive collapse of the upper respiratory tract during sleep, occurs in about 4% of middle-aged men and 2% of women. The incidence of the disorder is rising due to an increase in obesity and ageing of the population. Patients with obstructive sleep apnea are at elevated risk of some endocrinal and metabolic disorders, which may lead to serious consequences including shortening of life expectancy. The recognition and understanding of interactions between local upper airway dysfunction and its endocrinal consequences is therefore vital. In this review we will focus on the influence of OSA on bone metabolism and endocrine homeostasis. [ABSTRACT FROM AUTHOR]

Objective. The study was designed to evaluate the relationship between thyroid antibodies and gland dysfunction, with the aim of finding a clinically useful threshold value of thyreoperoxidase antibodies, which could prove to be predictive for thyroid failure. Materials and method. The study was conducted on 99 women, ages ranging from 18-91 years (mean age: 45.5 ±17.0), were treated as outpatients in the Department of Endocrinology, Metabolism and Internal Medicine. Analysis of serum samples for TSH concentration and anti-TPO titers was conducted. Results. The most common disorder was hypothyroidism. Anti-TPO titers above reference range values were observed in 35 patients (35.4%): 21 (60%) were hypothyroid and 11 (31.4 %) were euthyroid. The anti-TPO and TSH serum levels correlated both in patients with high thyroid antibody titers, and in the anti-TPO negative groups. To find the threshold value of antiTPO that would help predict hypothyroidism, receiver operating curves were used. With this approach, TPO antibody titers over 17 IU/ml indicated hypothyroidism with a 90% sensitivity and 75% sensibility. Conclusion. It can be postulated that the cutoff values of anti-TPO in the general population should be decreased in order to improve autoimmune thyroid disorder screening. Obviously, using that margin may lead initially to the detection of some false positive subjects. However, with lower cut-off values, more patients can be enrolled into thyroid follow-up groups. In this way, many people could avoid complications of undiagnosed, insidious thyroid failure. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists have been proposed for diagnostic imaging and radionuclide therapy—theranostics—of human tumors, including prostate (PC) and breast cancer (BC). We herein present [99mTc]Tc-DB15, a SPECT radiotracer based on the potent GRPR-antagonist [DPhe6,LeuNHEt13]BBN(6-13). After Sar11/Gly11-replacement an acyclic tetraamine was coupled at the N-terminus via a spacer allowing for stable binding of the diagnostic radiometal Tc-99m. The forming [99mTc]Tc-DB15 radiotracer displayed high in vitro uptake in GRPR-expressing mammary (T-47D) and prostate cancer (PC-3) cells. Furthermore, it showed an attractive biodistribution profile in mice bearing T-47D or PC-3 xenografts. A pilot proof-of-principle study of [99mTc]Tc-DB15 in PC and BC patients applying SPECT is currently under way. Promising results from the first two BC patients are presented herein. Diagnostic imaging and radionuclide therapy of prostate (PC) and breast cancer (BC) using radiolabeled gastrin-releasing peptide receptor (GRPR)-antagonists represents a promising approach. We herein propose the GRPR-antagonist based radiotracer [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DGA-DPhe6,Sar11,LeuNHEt13]BBN(6-13); N4: 6-carboxy-1,4,8,11-tetraazaundecane, AMA: aminomethyl-aniline, DGA: diglycolic acid) as a new diagnostic tool for GRPR-positive tumors applying SPECT/CT. The uptake of [99mTc]Tc-DB15 was tested in vitro in mammary (T-47D) and prostate cancer (PC-3) cells and in vivo in T-47D or PC-3 xenograft-bearing mice as well as in BC patients. DB15 showed high GRPR-affinity (IC50 = 0.37 ± 0.03 nM) and [99mTc]Tc-DB15 strongly bound to the cell-membrane of T-47D and PC-3 cells, according to a radiolabeled antagonist profile. In mice, the radiotracer showed high and prolonged GRPR-specific uptake in PC-3 (e.g., 25.56 ± 2.78 %IA/g vs. 0.72 ± 0.12 %IA/g in block; 4 h pi) and T-47D (e.g., 15.82 ± 3.20 %IA/g vs. 3.82 ± 0.30 %IA/g in block; 4 h pi) tumors, while rapidly clearing from background. In patients with advanced BC, the tracer could reveal several bone and soft tissue metastases on SPECT/CT. The attractive pharmacokinetic profile of [99mTc]DB15 in mice and its capability to target GRPR-positive BC lesions in patients highlight its prospects for a broader clinical use, an option currently being explored by ongoing clinical studies. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is a condition of breathing pathology occurring during sleep, characterized by repeated episodes of upper airway obstruction. The aim of the study was to determine the occurrence of airway obstruction in smoking males with OSA in whom lung function tests had not been performed before. One hundred and four current smokers selected from 1241 patients were enrolled for the research. The subjects included in the study smoked minimum 20 cigarettes a day for at least 10 years. The diagnosis of OSA was confirmed by polysomnography (PSG) in the Sleep Laboratory and subjects were assigned to one of three groups, depending on the severity of OSA. The control group consisted of 30 age-matched male smokers in whom OSA was not confirmed in PSG. Patients from the study and control group scored ≥ 11points in the Epworth Sleepiness Scale. Spirometry, impulse oscillometry, and body plethysmography were used to assess pulmonary function. Airflow limitation in subjects of the control group and OSA patients was confirmed. There were no significant differences in the incidence of bronchial obstruction between the control and study groups, and among the patients of various OSA severity. We conclude that the severity of OSA in smokers does not associate with the presence of airway obstruction. However, the increased peripheral respiratory resistance found in oscillometry did relate to a longer smoking time in OSA patients.

Hyperparathyroidism during pregnancy is diagnosed in 0.5-1.4% women and poses a serious challenge. Symptoms of primary hyperparathyroidism (PHP), namely fatigue, lethargy and proximal muscle weakness, are unspecific and could be mistaken as complaints naturally present during pregnancy. Thus, diagnosis is usually delayed. Moreover, the complications of PHP are very common. They occur in 67% of mothers and even in up to 80% of progeny. Appropriate management is a matter of debate. According to clinical symptoms, biochemical evaluation and trimester of pregnancy an operation or conservative management should be introduced. The recognition and understanding of the illness is therefore vital. Due to the lack of unequivocal guidelines concerning pregnancy and PHP, in this review we will analyze recent findings to facilitate proper proceedings.

The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.

Introduction: Acromegaly results from oversecretion of growth hormone and subsequently insulin growth factor-1. According to some authors, the disease can cause increased prevalence of nodular goitre and thyroid cancer (TC). However, the number of studies comparing acromegalic patients with control groups is low. We aimed to assess the prevalence of thyroid lesions in patients with acromegaly in comparison to an age- and sex-matched control group and to update the meta-analysis previously performed in our department by the same authors., Material and Methods: We searched medical documentation of patients with acromegaly treated in our department between 2003 and 2013. The prevalence of thyroid abnormalities was compared with the group of patients with hormonally inactive adrenal incidentalomas. To perform the meta-analytic part of the paper we also searched ten databases to find relevant papers., Results: Two hundred and five patients with acromegaly and 184 patients with incidentalomas were included. Any thyroid lesions were present in 77.6% of patients with acromegaly vs. 63.0% with incidentalomas (p = 0.002), multinodular goitre - 66.8% vs. 47.8% (p = 0.0002), and TC- 5.4% vs. 2.7% (p = 0.21) respectively. For thyroid lesions the pooled odds ratio (OR) was 3.1 (95% confidence interval [CI] 1.8-5.5), and for TCs the OR was 4.5 (95% CI 1.9-10.3)., Conclusions: According to our results thyroid lesions were significantly more common in patients with acromegaly; in case of TC the difference was not significant. The updated meta-analysis showed significantly increased prevalence of both disorders. In conclusion, systematic thyroid examination should be an important part of follow-up in case of acromegalic patients. (Endokrynol Pol 2017; 68 (1): 2-6).

INTRODUCTION Myeloid‑derived suppressor cells (MDSCs) have the potent ability to suppress T‑cell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD. PATIENTS AND METHODS The study included 64 patients with stable COPD. The clinical parameters of the patients were studied, and MDSCs were assessed using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. RESULTS The percentage of MDSCs in BALF was lower than that in PB (0.63 ±0.90 vs 3.94 ±0.38). In BALF, MDSCs (% of mononuclear cells) correlated with forced expiratory volume in 1 second (rs = -0.30, P = 0.0185), residual volume/total lung capacity (rs = 0.32, P = 0.0148), PaO2 (rs = -0.45, P = 0.0002), arterial oxygen saturation (SaO2; rs = -0.41, P = 0.0008), and diffusion capacity of carbon dioxide (rs = -0.32, P = 0.0211). There was a significant negative correlation between MDSCs (% of all leukocytes) and arterial oxygen pressure (rs = -0.42, P = 0.0006) and SaO2 (rs = -0.37, P = 0.0027). No correlations were found in PB. CONCLUSIONS MDSCs are present in human lung microenvironment and may be involved in local inflammation in COPD. Future studies should focus on a detailed assessment of MDSCs in local and systemic inflammation in COPD.