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ABSTRACT: Introduction: Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases. The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases. Material and methods: The study group consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA (R&D Systems) in all the study subjects. The statistical calculations were performed using MedCalc. Results: We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p 〈 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p 〈 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL. Conclusions: Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs. (Endokrynol Pol 2012; 63 (6): 470-476).
Endokrynologia Polska 01/2012; 63(6):470-6. · 1.24 Impact Factor
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ABSTRACT: Angiogenesis plays an important role in tumour growth, progression and invasiveness. Vascular endothelial growth factor (VEGF) is a recognised angiogenesis-stimulating factor. Soluble VEGF receptors (sVEGFRs) have antiangiogenic properties. Recent studies have indicated that serum concentrations of these factors show a good correlation with the aggressiveness of these tumours in various organs. The aim of this study was to assess the usefulness of determining serum concentrations of VEGF and sVEGFR-2 in patients with adrenal incidentalomas.
The study included 51 patients: 38 women aged 53.57 ± 10.12 years and 13 men aged 54.66 ± 12.73 years without a history of cancer but with non-functioning adrenal tumours incidentally detected on a CT scan. The analysis of the CT images included such morphological features of the tumour as: tumour size, tumour homogenicity, tumour density before and after administration of an intravenous contrast medium, and the value of percentage washout of the contrast medium from the tumour. Based on the above criteria, we identified a group of 40 patients with adrenal tumours who met the CT criteria for benign adenomas (Group 1) and 11 patients whose incidentally discovered tumours did not meet the radiological criteria for benign adenomas, thereby providing grounds for referring these patients for surgery (Group 2). The control group consisted of 20 healthy sex- and age-matched individuals.
The mean serum concentrations of VEGF in the study and control groups were similar, although patients with adrenal tumours had significantly higher concentrations of sVEGFR-2 than healthy individuals. There were no significant differences in the mean concentrations of VEGF and sVEGFR-2 between the patients undergoing surgery (Group 2) and the patients not undergoing surgery (Group 1), or between the patients undergoing surgery (Group 2) and the control group. Postoperative histopathology of the resected adrenal tumours revealed benign adrenocortical adenoma in eight patients and the following in the remaining patients: adrenocortical carcinoma in one patient, phaeochromocytoma in one patient and ganglioneuroma in one patient. The adrenocortical carcinoma patient had the highest concentration of VEGF, while this patient's concentration of sVEGFR-2 was the lowest in the study group. In the patients diagnosed with ganglioneuroma and phaeochromocytoma, VEGF and sVEGFR-2 concentrations did not differ significantly from their mean concentrations in the study group. There were also no relationships between the serum concentrations of VEGF or sVEGFR-2 and the following parameters: tumour size, precontrast and postcontrast tumour densities or the value of percentage washout. Positive correlations were, however, identified between the concentration of VEGF and the concentrations of total cholesterol and LDL-cholesterol.
Determining the serum concentrations of such angiogenesis markers as VEGF and sVEGFR-2 seems useful in the evaluation of the nature of incidentally detected adrenal masses (incidentalomas), especially in the preoperative differential diagnosis of adrenal masses that do not meet the CT criteria for benign tumours.
Endokrynologia Polska 01/2012; 63(1):22-8. · 1.24 Impact Factor
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ABSTRACT: The increased incidence of cardiovascular disease in women with polycystic ovary syndrome (PCOS) has prompted researchers to look for indicators of early atherosclerotic changes in these patients. One of the earliest stages of atherogenesis is endothelial cell dysfunction. The aim of this study was to assess the levels of selected plasma markers of endothelial injury [E-selectin, endothelin-1 (ET-1) and von Willebrand Factor antigen (vWF:Ag)] in PCOS women before and after six months of treatment.
32 patients with PCOS aged 18-36 years (mean age 25.16 ± 5.80) were included in the study. The control group consisted of 20 healthy women matched for age and body mass. The levels of ET-1, vWF:Ag, E-selectin, fasting glucose, insulin, total cholesterol, HDL and LDL-cholesterol and triglycerides were assessed. In the PCOS group, all these tests were repeated after six months of treatment.
The study showed higher levels of vWF:Ag (p = 0.043), E selectin (p = 0.028), insulin (p = 0.044), glucose (p = 0.036) and LDL (p = 0.006) in PCOS patients versus healthy women. A positive correlation was demonstrated between E selectin and glucose (p = 0.0001), triglycerides (p = 0.014) and uric acid (p = 0.008). vWF:Ag levels showed a positive correlation with glucose (p = 0.04) and triglycerides (p = 0.036). A positive correlation was also found between ET-1 and total cholesterol levels (p = 0.012) in PCOS women. After treatment, there was a significant reduction in E-selectin levels from baseline (p = 0.002) and an increase in the levels of HDL (p = 0.0002) and triglycerides (p = 0.033).
Elevated levels of vWF:Ag and E selectin in PCOS women suggest endothelial dysfunction in this group of patients. Glucose and triglyceride are significant factors affecting endothelial function in PCOS.
Endokrynologia Polska 01/2011; 62(3):243-8. · 1.24 Impact Factor
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ABSTRACT: Pathogenesis of colonic lesions in patients with acromegaly remains still unclear. There are suggestions that apart from somatotropin axis hormones (GH and IGF-1), other agents also take part in this process. Molecular and animal studies indicate a vital role of hyperinsulinemia in development of colorectal neoplasms.
To evaluate a relation between insulin level, insulin resistance and its anthropometric markers and colorectal lesions in patients with acromegaly.
The study consisted of 40 patients with active, newly diagnosed acromegaly; 24 women and 16 men aged from 24 to 77 years (mean age 50.1, SD+/-12.1). The analysis included the results of somatotropin axis function (GH and IGF-1 level), carbohydrate metabolism assessment (fasting serum glucose and insulin levels, oral glucose tolerance test, HOMA-IR for insulin resistance), the results of anthropometric measurement (BMI, WHR) and colonoscopy.
Colon pathologies (60 polyps and 2 flat lesions) were discovered in 19 (47.5%) patients with acromegaly, 8 of them had multiple polyps. Hyperplastic polyps were revealed in 11 (27.5%), while adenomas in 8 (20%) acromegalics. Patients with colorectal lesions were found to have higher WHR then subjects with normal colon (p=0.033). Positive correlation between the number of hyperplastic polyps in the patients with multiple changes in the colon and IGF-1 (p=0.025), insulin level (p=0.005) and HOMA-IR (p=0.001) was found. Multiple adenomas correlated positively with insulin level (p=0.007), HOMA-IR (p=0.006) and BMI (p=0.015).
The study results show a relation between hyperinsulinemia, insulin resistance and colon pathologies in acromegaly. Fasting insulin level and HOMA-IR correlate positively with the number of hyperplastic polyps and adenomas in acromegalic patients with multiply colorectal lesions.
Neuro endocrinology letters 03/2008; 29(1):107-12. · 1.30 Impact Factor
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Violetta Matyja,
Beata Kos-Kudla,
Wanda Foltyn, Janusz Strzelczyk,
Wojciech Latos,
Bogdan Marek,
Dariusz Kajdaniuk,
Jacek Karpe,
Zofia Ostrowska,
Karolina Sieron-Stoltny,
Aleksander Sieron
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ABSTRACT: Acromegalics have an increased risk of colorectal neoplasm. The aim of this study was to establish the association between acromegaly and colorectal lesions.
The study included 51 patients with active acromegaly: 30 women and 21 men (average age 52.95 +/- 13.49 years). Growth hormone (GH), insulin-like growth factor I (IGF-I), prolactin (PRL), thyreothropin (TSH), thyroxine (FT4) were measured in the serum when patients were hospitalized for their first diagnosis of acromegaly, before starting the treatment. All patients underwent colonoscopy--in the first phase conventional in white light; in the second phase fluorescence colonoscopy. Autofluorescence of colonic mucosa was assessed by illumination with monochromatic light. Green fluorescence is characteristic for normal colonic mucose, whereas red fluorescence occur in pathological lesions. Material to histopathological examination was taken from every pathological colorectal lesion.
Using conventional colonoscopy we detected colonic polyps in 21 acromegalic patients (41.17%). Polyps with red fluorescence were found in 7 (13.7%) acromegalics and with green fluorescence in 16 (31.37%) cases of these patients. Histological diagnoses of colorectal lesions are adenoma, hyperplastic and inflammatic polyps. The number of colorectal polyps was dependent on IGF-I, fT4 and sex.
Acromegaly is associated with high prevalence of colorectal pathology, mainly hyperplastic polyp and adenoma. There is a relationship between number of colorectal polyps and serum IGF-I levels in acromegaly. Adenomas and hyperplastic polyps were associated with higher levels of IGF-I.
Neuro endocrinology letters 11/2006; 27(5):639-43. · 1.30 Impact Factor
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ABSTRACT: The aim of the study was pineal gland function assessment on the base of daily rhythm study and mean daily melatonin (MEL) concentrations in serum in patients with colorectal carcinoma.
Studies were performed in 12 women at the age of 63.17+/-5.90 years and 21 men aged 58.95+/-11.32 years with large intestine adenocarcinoma. The control group consisted of 28 healthy volunteers at comparable age. During the circadian study blood samples for the measurement of melatonin (MEL) were collected every 4 hours during 12 h. MEL concentrations were assessed with the use of RIA methods. Statistical analysis of circadian rhythms of MEL was carried out with the use of cosinor method according to Halberg.
Existence of daily rhythm of MEL secretion was shown in all studied groups. A significant decrease of amplitude of rhythm and secretion of MEL at nocturnal hours in comparison with the control group was shown in the group of women with large intestine carcinoma. A significant decrease of mesor value and amplitude of MEL rhythm as a consequence of decrease of MEL secretion at nocturnal and morning hours was observed in the group of ill men.
Decrease in melatonin circadian rhythm amplitude as a consequence of its lowered nocturnal secretion occurred in all patients with colorectal carcinoma. Abnormalities in daily rhythm of melatonin secretion were more intensified in men with large intestine carcinoma, which leads to suppression of mean daily hormone concentration.
Neuro endocrinology letters 07/2002; 23(3):239-42. · 1.30 Impact Factor
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ABSTRACT: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.
The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).
The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.
Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy.
Neuro endocrinology letters 05/2002; 23 Suppl 1:104-9. · 1.30 Impact Factor
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ABSTRACT: Prolonged glucocorticoids administration is the most common cause of secondary osteoporosis. It is estimated that 30% to 50% of chronic glucocorticoids users experience vertebral or hip fractures. The highest bone loss (up to 30% in some studies) is observed in the first six months of treatment. Only a minority of patients who take chronic glucocorticoids receive optimal osteoporosis diagnosis, prevention, and/or treatment. The aim of this paper is to present the pathophysiology of glucocorticoid-induced osteoporosis, as well as some guidelines on diagnostic, preventive and therapeutic strategies for this disorder in an effort to promote the greater awareness of it.
Endokrynologia Polska 58(2):170-5. · 1.24 Impact Factor
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ABSTRACT: It is well known that there is a higher prevalence of cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women. Recently it has become evident that adiponectin and leptin secreted by adipose tissue may be involved in the pathophysiology of MS. The aim of the study: was to assess the effects of the menopause on the relationships between adiponectin and leptin and different cardiovascular and metabolic risk factors.
A total of 56 postmenopausal women and 75 premenopausal subjects were enrolled in this study. We measured blood pressure, BMI, waist circumference and WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and fasting glucose and applied the oral glucose tolerance test (OGTT). Women were categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3 abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by the radioimmunoassay (RIA) method.
A decline in adiponectin was related to an increased number of MS variables in postmenopausal and premenopausal women. Postmenopausal women with MS had significantly lower adiponectin concentrations than premenopausal women with MS. Serum adiponectin concentrations were inversely correlated to leptin in postmenopausal women. In premenopausal women no clear relationships were found between serum leptin and the number of metabolic disturbances. In contrast to young women, postmenopausal women showed an increase in leptin secretion with a growing number of MS elements. Compared to premenopausal women with MS, postmenopausal women with MS had higher levels of leptin. We found associations between leptin and different risk factors, mainly in the postmenopausal group. When the presence of MS was used as a dependent variable (yes/no) and adiponectin, leptin and menopause status as independent factors, adiponectin and leptin remained significant variables related to MS.
The significant role of adiponectin in the pathophysiology of MS in premenopausal and postmenopausal women is confirmed in this study. Leptin is correlated with several MS components but this adipocytokine appears to play a role only in postmenopausal women.
Endokrynologia Polska 57(1):15-22. · 1.24 Impact Factor
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ABSTRACT: Chromogranin A (CgA) is a non-specific marker of neuroendocrine tumors (NET) and is important in monitoring the disease course and NET treatment.
Usefulness of suppression test of CgA secretion with octreotide in diagnosis and predicting the therapy outcome in NET patients.
The study included 32 patients with NET of gastrointestinal tract, lung and of unknown origin. CgA level in blood plasma on fasting, before and 30, 60, 90 and 120 minutes after subcutaneous administration of 100 mug octreotide, was determined in all patients. The subjects were divided into two subgroups with relation to CgA level and to the results of somatostatin receptor scintigraphy (SRS).
Statistically significant CgA decrease after octreotide administration in all study time points and positive results of SRS were found in the patients with the elevated CgA level. No statistically significant decrease of CgA level after octreotide was found in the group with normal CgA levels. In this group, 13 patients had a negative result of SRS, and somatostatin receptors expression was found in one patient. Tolerance of somatostatin analogs (SSA) therapy was very good.
Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. This examination can also be a screening test useful in planning the treatment with SSA in patients with NET.
Endokrynologia Polska 58(2):123-9. · 1.24 Impact Factor
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Mariusz Nowak,
Tomasz Wielkoszyński,
Beata Kos-Kudła,
Bogdan Marek,
Jacek Karpe,
Dariusz Kajdaniuk,
Lucyna Siemińska,
Joanna Głogowska-Szelag,
Wanda Foltyn, Janusz Strzelczyk,
Katarzyna Nowak
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ABSTRACT: The soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) have been found to be increased in the blood of patients with Graves disease. The aim of this study is evaluation of the serum concentrations of soluble forms of adhesion molecules ICAM-1 and VCAM-1 in patients with thyroid-associated orbitopathy (TAO) before and after methylprednisolone treatment.
The study was performed in 40 Graves disease, hyperthyroid and euthyroid patients with a clinically active form of TAO. Serum concentrations of sVCAM-1 and sICAM-1 in TAO patients were determined by enzymelinked immunoabsorbent assay (ELISA) before and after intensive pulse methylprednisolone treatment.
We did not find any significant changes in the studied parameters between TAO patients with hyperthyroidism and those with euthyroidism. The serum concentrations of sICAM-1 and sVCAM-1 were significantly increased in patients with TAO before methylprednisolone therapy when compared with the control group. After treatment serum concentrations of sICAM-1 and sVCAM-1 decreased significantly but were still significantly higher than for the control group.
From the results obtained we can conclude that Graves orbitopathy itself but not thyroid function is probably responsible for the elevated level of the adhesion molecules studied.
Endokrynologia Polska 58(6):487-91. · 1.24 Impact Factor
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ABSTRACT: Neuroendocrine tumors are frequently associated with other primary malignancies. Plasmablastic lymphoma is a rare, aggressive neoplasm, derived from large B-cell, associated with human immunodeficiency virus infection. Plasmablastic lymphoma cells share many cytomorphologic and immunophenotypic features with plasmablastic cells, causing some diagnostic problems. We present a unique case of coexisting two very uncommon neoplasms: plasmablastic lymphoma and neuroendocrine carcinoma in 54-years-old men. This is the first report of caecum localization of plasmablastic lymphoma. Presented case images diagnostic problems in rare neoplasms.
Endokrynologia Polska 57(2):160-5. · 1.24 Impact Factor
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ABSTRACT: Leptin and adiponectin are involved in the pathogenesis of several autoimmune diseases. Very little is known about adipocytokine production in autoimmune thyroid diseases. Interleukin-6 (IL-6) plays an important role in the inflammatory and autoimmune processes.
The aim of this study was to assess the serum levels of leptin, adiponectin, and IL-6 in postmenopausal euthyroid women with Hashimoto's thyroiditis and compared them with concentrations in control women. Ninety-eight euthyroid women with Hashimoto's thyroiditis were enrolled in the study. The diagnosis was confirmed with elevated thyroid peroxidise autoantibody (TPOAb) levels in serum and typical hypoechogenic pattern on thyroid ultrasound. The control group, matched for body mass index (BMI), consisted of 105 healthy postmenopausal euthyroid women. Serum levels of leptin, adiponectin, IL-6, thyroid-stimulating hormone (TSH), free thyroxine (fT(4)), and TPOAbs were determined.
When compared with controls, the women with Hashimoto's thyroiditis were characterized by significantly elevated serum concentrations of IL-6, whereas concentrations of leptin and adiponectin were not different. Hashimoto's thyroiditis patients had significantly higher serum levels of TSH than the controls. The simple linear regression analyses of the Hashimoto's thyroiditis group and all of the studied women indicated that serum leptin levels correlated positively with BMI, waist to hip ratio (WHR), TSH, and IL-6 and negatively with adiponectin. No correlation was observed between serum adiponectin and TSH, fT(4), or TPOAbs. There were no associations between serum IL-6 levels, TPOAbs, and TSH levels; however, positive correlations between IL-6 and BMI, WHR, and leptin were observed. TSH correlated positively with leptin, age, and TPOAbs.
Hashimoto's thyroiditis is characterized by an increased production of IL-6 but does not have a direct influence on leptin or adiponectin serum levels. The correlations between TSH and leptin demonstrated in this study highlight the need for future investigations. (Pol J Endocrinol 2010; 61 (1): 112-116).
Endokrynologia Polska 61(1):112-6. · 1.24 Impact Factor
