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Zorica Sumarac,
Nada Suvajdžić,
Svetlana Ignjatović,
Nada Majkić-Singh,
Dragana Janić, Milan Petakov,
Maja Dorđević,
Mirjana Mitrović,
Marijana Dajak,
Milka Golubović,
Predrag Rodić
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ABSTRACT: The aim of the study was to evaluate the efficiency of the biomarkers chitotriosidase (Chito), total acid phosphatase (TACP), angiotensin converting enzyme (ACE) and ferritin in the diagnosis of Gaucher disease (GD) and to assess the utility of biomarkers for monitoring the effects of enzyme replacement therapy (ERT).
Forty treatment-naive Gaucher patients were studied. 27/40 GP were put on ERT and monitored every 6 months.
The baseline median values of Chito, TACP, ACE and ferritin were highly elevated in GP: 10216 nmol/mL/h, 26.1 U/L, 253 U/L, 515 μg/L, and 555 μg/L, respectively. The only significant difference between mild and moderate GP subgroups is observed for Chito activity (p=0.0116). During ERT, Chito showed the steepest decrease in regard to TACP and ACE, mainly within the first year (71.4%).
Among these biomarkers, Chito proved to be the most useful biomarker for diagnosing GD and monitoring the ERT.
Clinical biochemistry 05/2011; 44(12):950-4. · 2.02 Impact Factor
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Marina Djurović,
Svetozar Damjanović,
Svetislav Tatić,
Marjan Micev,
Aleksandar Cetković, Milan Petakov,
Vladimir Djukić,
Dragana Miljić,
Sandra Pekić,
Mirjana Doknić,
Marko Stojanović,
Aleksandar Vuksanović,
Vera Popović
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ABSTRACT: Carcinoid tumors are distinct neuroendocrine neoplasms commonly located within the gastrointestinal tract and bronchopulmonary system. The aim of this case report was to present a patient with carcinoid tumor of the ovary as a less common form of this neoplasm.
A 49 year old woman was admitted to the hospital with symptoms of diarrhea and abdominal pain and suspicion of neuroendocrine neoplasm, 4 month after bilateral salpingo-oophorectomy and total hysterectomy for ovarian tumor. Pathological diagnosis was typical for carcinoid tumor. At admission the patient had slightly eleveated levels of tumor marker CA 125 and highly elevated levels of 5- HIAA. Abdominal CT showed suspicious rest tumor in the pelvis. Relaparotomy was done and retroperitoneal fibrosis was found. Six months after the intervention the levels of 5-HIAA and CA 125 were normal, and NMR of the abdomen showed no signs of rest tumor.
Carcinoid tumor of the ovary is rare form of ovarian tumors and less than 0.1% had malignant potential. Surgical therapy associated with a long-term followup was the treatment of choice. Consideration of unusual sites of carcinoid tumors facilitates appropriate diagnosis and treatment.
Vojnosanitetski pregled. Military-medical and pharmaceutical review 03/2011; 68(3):274-6. · 0.18 Impact Factor
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Djuro Macut,
Danijela Vojnović Milutinović,
Ivana Božić,
Gordana Matić,
Jelena Brkljačić,
Dimitrios Panidis, Milan Petakov,
Nikolaos Spanos,
Jelica Bjekić,
Olivera Stanojlović,
Anđela Petrović Milinković,
Zoran Radojičić,
Svetozar Damjanović
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ABSTRACT: Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 ± 5.1 years, mean body mass index (BMI) 24.5 ± 5 kg/m(2)], and thirty respective controls were analyzed for the number of GR sites per cell (B (max)), apparent equilibrium dissociation constant (K (d)), and binding potency (GR potency). A strong association between B (max) and K (d) (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K (d) were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.
Endocrine 02/2010; 37(1):129-34. · 1.42 Impact Factor
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ABSTRACT: The role of cortisol in mediating basal metabolic rate (BMR) changes that accompany the adjustment of maternal body weight (BW) and body composition during pregnancy is unknown. We tested whether increase in BMR during pregnancy is explained by variations in cortisol secretion. Longitudinal changes in BW, fat mass (FM), fat-free mass (FFM), BMR, hormonal, and metabolic parameters in 31 parous Caucasian women at gestational weeks 12, 26, and 36 were examined. Individual differences (Delta) between the last and the first measurement occasions for each variable were calculated. By gestational week 36, BW and BMR increased while both FFM/FM and BMR/BW ratio decreased (P < 0.001 for all) suggesting higher proportion of FM accretion. Cortisol, leptin, and insulin-like growth factor-1 (IGF-1) concentration rose, whereas non-placental growth hormone (GH) and thyroid hormones declined (P < 0.001 for all). Insulin resistance changed; basal glucose (P < 0.001) and ghrelin (P < 0.014) declined, whereas insulin (P < 0.001), homeostatic model index (HOMA-IR) (P = 0.041), and free fatty acid (FFA) concentration (P = 0.007) increased. The elevation in BMR showed inverse correlations with DeltaBW (r = 0.37, P = 0.047) and Deltacortisol (r = -0.53, P = 0.004). Significant portion (51.6%) of the variation in BMR change was explained by increases of cortisol (27.1%), FFA (13.4%), and free triiodothyronine (11.1%). In conclusion, the changes in maternal cortisol concentration are in relationship with changes in BMR and BW, further suggesting that increased cortisol secretion during pregnancy could be linked with the maintenance of maternal BW and body composition.
Endocrine 01/2009; 35(2):262-8. · 1.42 Impact Factor
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Djuro Macut,
Dimitrios Panidis,
Biljana Glisić,
Nikolaos Spanos, Milan Petakov,
Jelica Bjekić,
Olivera Stanojlović,
David Rousso,
Anargyros Kourtis,
Ivana Bozić,
Svetozar Damjanović
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ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by obesity-related risk factors for cardiovascular disease. The objective of our study was to determine values of key lipid and lipoprotein fractions in PCOS, and their possible relation to insulin resistance. A total of 75 women with PCOS (aged 23.1 +/- 5.1 years, BMI 24.9 +/- 4.7 kg/m(2)), and 56 age- and BMI-matched controls were investigated. In all subjects, basal glucose, cholesterol (total, HDL, and LDL), oxidized LDL (OxLDL), triglycerides, apolipoprotein (apo)A1, apoB, and apoE, nonesterified fatty acids, insulin, testosterone, sex hormone-binding globulin, homeostasis model assessment (HOMA) index, and free androgen index were determined in the follicular phase of the cycle. PCOS patients compared with controls had increased indices of insulin resistance, basal insulin (p < 0.001), and HOMA index (p < 0.001), and worsened insulin resistance-related dyslipidemia with decreased HDL cholesterol (p < 0.01), elevated triglycerides (p = 0.010), and pronounced LDL oxidation (p < 0.001). In conclusion, characteristic dyslipidemia of insulin resistance and unfavorable proatherogenic lipoprotein ratios were present only in women with PCOS and not in controls. Elevated OxLDL and the relation of apoE and nonesterified fatty acids with insulin resistance suggest that women with PCOS are at increased risk for premature atherosclerosis.
Canadian Journal of Physiology and Pharmacology 04/2008; 86(4):199-204. · 1.95 Impact Factor
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ABSTRACT: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS.
Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined.
Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein-A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined.
Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P = 0.007 and 0.003 respectively). Both the basal insulin (P = 0.003) and HOMA values (P < 0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P < 0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P < 0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3-16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P < 0.001, OR 2.8; 95% CI 1.6-4.9).
Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.
European Journal of Endocrinology 08/2006; 155(1):131-6. · 3.42 Impact Factor
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ABSTRACT: The study aim was to investigate the relationship between insulin resistance (IR), beta-cell function (betaF), hyperandrogenism and proinsulin levels during an oral glucose tolerance test (OGTT) in women with polycystic ovary syndrome (PCOS).
One hundred and twenty-six selected women were classified as follows: PCOS, BMI > 25 kg/m2 (n = 39); PCOS, BMI < 25 kg/m2 (n = 54); controls, BMI > 25 kg/m2 (n = 14); controls, BMI < 25 kg/m2 (n = 19). Blood samples were collected between the third and sixth day of a spontaneous menstrual cycle, at 9:00 a.m., after an overnight fast. Serum levels of FSH, LH, PRL, 17alpha-OH-progesterone, SHBG, testosterone, delta4-androstenedione, insulin, proinsulin and glucose were measured. A 75 g OGTT was performed, and concentrations of glucose, insulin and proinsulin were also measured at t = 30, 60, 90, and 120 min.
The markers of insulin secretion and the AUC for proinsulin were higher in obese and overweight women and in women with PCOS, respectively. The AUC for proinsulin was positively correlated with markers of IR, betaF and androgen levels. An inverse relationship between PI/I values and indices of IR and betaF was observed.
Increased proinsulin levels reflect, most probably, insulin resistance, which is the key disorder in PCOS-associated metabolic abnormalities. Beta-cell function, pre-proinsulin mRNA processing and proinsulin conversion to insulin could be initially increased as a result of IR. An interaction between circulating proinsulin and androgen biosynthesis or action might also exist.
European Journal of Obstetrics & Gynecology and Reproductive Biology 07/2006; 127(1):99-105. · 1.97 Impact Factor
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ABSTRACT: We report the case of a 52-yr-old man with a mass in the area of the left adrenal. The clinical features, MIBG uptake, and elevated urinary dopamine levels suggested the diagnosis of pheochromocytoma. He presented with unstable hypertension, tachycardia, weight loss, and the "inflammatory syndrome" (fever, leukocytosis, and high sedimentation rate). Clinical findings, preoperative radiographic (sonography, CT scan, [131I]MIBG scintigraphy), and endocrine evaluations (elevated 24-h urinary dopamine) were suggestive of a dopamine-secreting adrenal tumor. The mass was resected and on histologic examination showed the characteristic features of a malignant fibrous histiocytoma (MFH). The tumor cells were immunopositive for neuron-specific enolase (NSE), vimentin, CD-68, S-100, desmin, and immunonegative for chromogranin A, synaptophysin, neurofilament protein, and low-molecular-weight keratin, indicating that this tumor was not able to synthesize catecholamines. The prolonged retention of the tracer (MIBG) was interpreted as a consequence of obstructive hydronephrosis, while elevated urinary dopamine levels were assumed to be due to compression of the renal vessels by the large retroperitoneal mass.
Endocrine 07/2004; 24(1):99-103. · 1.42 Impact Factor
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Vera Popovic,
Marina Djurovic,
Aleksandar Cetkovic,
Danilo Vojvodic,
Sandra Pekic,
Svetlana Spremovic, Milan Petakov,
Svetozar Damjanovic,
Natasa Milic,
Carlo Dieguez,
Felipe F Casanueva
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ABSTRACT: Inhibin B is a product of the gonads and a marker for ovarian follicular development. This was a cross-sectional study designed to assess awakening of the reproductive function by studying secretion pattern of inhibin B during the weight restoration in patients with anorexia nervosa (AN). Twenty patients with AN participated at low weight [body mass index (BMI) 14.3 +/- 0.3 kg/m(2))], 22 partially weight recovered AN (BMI 17.4 +/- 0.1 kg/m(2)), 16 reached goal weight but did not restore menstrual cycles (BMI 19.5 +/- 0.1 kg/m(2)), and 13 reached goal weight and had at least six consecutive menstrual cycles (BMI 19.3 +/- 1.0 kg/m(2)). Nineteen eumenorrheic females with BMI 19.8 +/- 0.4 kg/m(2) served as controls. At low weight, patients had low basal leptin, inhibin B detectable in only 15% of samples, and LH significantly lower than in controls (P < 0.01). At weight gain, basal leptin increased, median inhibin B increased (detectable in 66.7% of samples), and LH remained low, all significantly lower than in controls (P < 0.01). Weight-recovered/amenorrheic patients further increased basal leptin, inhibin B was detectable in all samples, and LH remained low, all significantly lower than in controls (P < 0.01). In weight-recovered/cycling patients, basal leptin, median inhibin B, and LH, as expected, were not different from healthy volunteers. Inhibin B values correlated significantly with leptin (P = 0.000) and BMI (P = 0.000). In summary, gonads in patients with AN who gain weight are not entirely quiescent but have a low level of activity. Inhibin B is an early marker of gonadal activity, and with weight gain, awakening of the reproductive function is gradual, whereas factors triggering the onset of menstrual cycles still remain unknown (nutritional fat intake, psychological).
Journal of Clinical Endocrinology & Metabolism 04/2004; 89(4):1838-43. · 6.50 Impact Factor
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ABSTRACT: A 70-year old female was admitted to the hospital because of hypertension increased sweating and weight loss. The hypertension was sustained. Five months before admission CT scan of the abdomen had revealed a well-defined right adrenal mass together with left kidney tumor. A magnetic resonance imaging of the abdomen confirmed the presence of the right adrenal and left kidney masses, but also showed another tumor in the pancreas between the body and the tail. Urinary 24-hour noradrenaline was grossly elevated and confirmed the diagnosis of pheochromocytoma. 131I-metaiodobenzylgvanidine (MIBG) scintiscan showed increased MIBG uptake in the right adrenal gland. After pre-treatment with phenoxybenzamine 30 mg daily, the patient was operated, and the right adrenalectomy was done. Histopathological examination revealed encapsulated adrenal pheochromocytoma without infiltrative characteristics and lymph node metastasis. After the operation hypertension was controlled easily with amlodipine. The patient was discharged for recovery. Ulteriorly, SSCP (single strand conformational polymorphism) method detected a point mutation in the third exon of the VHL (von Hippel-Linday) gene. It was decided to follow up the patient with the von Hippel-Lindau disease, while waiting for the results of the sequence analysis to confirm that the found mutation is not associated with renal cancer.
Archive of Oncology. 01/2003;
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Archive of Oncology. 01/2002;
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ABSTRACT: The aim of this study was to evaluate the influence of circulating cortisol levels on the somatotroph responsiveness to the most potent stimuli of growth hormone (GH) secretion, the GHRH+GHRP-6 test. We studied 12 patients with hypocortisolism (10 with Addison's disease and 2 with isolated ACTH deficiency) before and after glucocorticoid (GC) replacement therapy and compared them with 14 healthy subjects. In the 10 patients with Addison's disease, GH responses (GH peak, microg/L) to GHRH+GHRP-6 were similar both during GC, (68.2+/-12.8) and off GC (60.3+/-14.1) therapy and did not differ from those in controls (61.5+/-6.0). In a subgroup of 4 patients with newly diagnosed Addison's disease, GH responsiveness to GHRH+GHRP-6 prior to GC replacement (26.4+/-4.1) was significantly lower than in the 6 patients with long-standing Addison's disease after short-term GC withdrawal (82.9+/-18.2). In the newly diagnosed Addison's patients, after one month of GC replacement, mean GH peak value increased to 40.7+/-11.8. In the 2 patients with isolated ACTH deficiency, GH responses to GHRH+GHRP-6 did not differ off and on GC therapy (60.3+/-14.1 and 41.5+/-2.0, respectively). Our data suggest that short-term GC deprivation does not have a major impact on GH responsiveness to GHRH+GHRP-6. However, in patients with long-standing hypocortisolism, GH response is blunted but still within normal range (> 15 microg/L).
Hormones (Athens, Greece) 2(4):243-9. · 2.44 Impact Factor
