Uloga omjera E2/P u etiologiji fibrocistične bolesti dojke, mastalgije i mastodinije

The aim of the study was to assess the role of the estradiol and progesterone relationship during the late luteal phase and the occurrence of fibrocystic breast disease (FBD). The concentration of estradiol/progesterone was measured in the group of women with FBD as study group (n=50) and control group of women without FBD (n=40). All women had regular ovulation cycles. Blood samples for estradiol (E2), progesterone (P) and prolactin determination were obtained in the morning at 8 am on days 21 and 24 of menstrual cycle. Significant mastalgia and mastodynia history in women with FBD was obtained with yes or no questionnaire. FBD diagnosis was confirmed with ultrasound (size and number of simple cysts). In the control group, a reduced E2/P ratio was noticed from day 21 to day 24 of the cycle (from 14.8±11.5 pg/mL to 9.1±6.1 pg/mL; p<0.05), which was not recorded in the group of women with FBD (study group). Even the slightest disturbance of the E2/P ratio may contribute to the occurrence of FBD with clinical manifestations of mastalgia and mastodynia.Namjera rada je bila ispitati ulogu odnosa estradiola i progesterona za vrijeme lutealne faze ciklusa u pojavljivanju fibrocistične bolesti dojke (FBD). Koncentracija odnosa estradiol/progesteron je bila mjerena u skupini žena s FBD (n=50) (studijska skupina) i u kontrolnoj skupini žena bez FBD (n=40) (kontrolna skupina). Sve su žene imale redovite ovulacijske cikluse. Krvni uzorci estradiola (E2), progesterona (P) i prolaktina određivali su se u 8 h ujutro 21. i 24. dana menstruacijskog cikusa. Određivanje značajnosti mastalgije i mastodinije bila je ispitana upitnikom da/ne. Dijagnoza FBD je bila potvrđena ultrazvukom dojke (veličina i broj jednostavnih cista). U kontrolnoj skupini smanjen odnos E2/P zabilježen je od 21. do 24. dana ciklusa (od 14,8±11,5 pg/mL do 9,1±6,1 pg/mL; p<0,05), za razliku od žena studijske skupine gdje ta promjena nije bila zapažena. Čak i mala promjena odnosa E2/P može doprinijeti nastanku FBD s kliničkim manifestacijama mastalgije i mastodinije

Small bowel adenocarcinoma mimicking a large adrenal tumor

Introduction. Adenocarcinoma of the small bowel is a rare gastrointestinal neoplasm usually affecting the distal duodenum and proximal jejunum. Because of their rarity and poorly defined abdominal symptoms, a correct diagnosis is often delayed. Case Outline. We present a 43-year-old woman admitted at the Clinic for Endocrinology due to a large tumor (over 7 cm) of the left adrenal gland. The tumor was detected by ultrasound and confirmed by CT scan. The patient complained of abdominal pain in the left upper quadrant, fatigue and septic fever. Normal urinary catecholamines excluded pheochromocytoma. The endocrine evaluations revealed laboratory signs of subclinical hypercorticism: midnight cortisol 235 nmol/L, post 1 mg - overnight Dexamethasone suppression test for cortisol 95.5 nmol/L and basal ACTH 4.2 pg/mL. Plasma rennin activity and aldosterone were within the normal range. Surgery was performed. Intraoperative findings showed signs of acute peritonitis and a small ulceration of the jejunum below at 70 cm on the anal side from the Treitz’s ligament. Adrenal glands were not enlarged. Patohistology and immunochemistry identified adenocarcinoma of the jejunum without infiltration of the lymphatic nodules. The extensive jejunal resection and lavage of the peritoneum were performed. Due to complications of massive peritonitis, the patient died seven days after surgery. Conclusion. Poorly defined symptoms and a low incidence make the diagnosis of small bowel carcinoma, particularly of the jejunal region, very difficult in spite of the new endoscopic techniques

Collagen type I alpha 1 gene polymorphism in premature ovarian failure

Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.Projekat ministarstva br. ON 17305

Collagen type I alpha 1 gene polymorphism in premature ovarian failure

Introduction. Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.Uvod. Prevremena insuficijencija jajnika (PIJ) se odlikuje amenorejom, hipergonadotropizmom i hipoestrogenijom kod žena mlađih od 40 godina. Osteoporoza je kasna komplikacija ovog stanja. Cilja rada. Cilj istraživanja je bio da se uporede genski polimorfizam kolagena tip I alfa 1 (COLIA1) sa gustinom koštane mase kod žena sa PIJ. Metode rada. Određivan je COLIA1 genotip SS, Ss i ss kod 66 žena sa PIJ pomoću eseja za reakciju lančanog umnožavanja DNK (engl. polymerase chain reaction - PCR). Polimorfizam jednog nukleotida (zamena G u T) u okviru Sp1 vezujućeg mesta u prvom intronu gena COLIA1 određivan je primenom PCR, nakon čega se pristupilo analizi konformacionog polimorfizma. Gustina koštane mase je merena na nivou lumbalnog dela kičme pomoću apsorpciometrije. Hormonske analize za folikulostimulišući hormon, luteinizirajući hormon, estradiol, prolaktin, progesteron i testosteron urađene su primenom metoda RIA. Pri statističkoj obradi podataka korišćeni su: Kraskal-Volisov (Kruskal-Wallis) ANOVA test, χ2-test i Spirmanov (Spearman) test korelacije. Rezultati. Relativna distribucija alela COLIA1 genotipa bila je: SS 54,4%, Ss 41,0% i ss 4,5%. Nije utvrđena značajna razlika između grupa prema genotipu za gustinu koštane mase, starost ispitanica, period amenoreje ili indeks telesne mase žena. Značajna pozitivna korelacija je uočena za indeks telesne mase i paritet. Zaključak. COLIA1 je samo jedan od mnogih gena koji utiču na karakteristike kosti. Kod žena starije životne dobi on može biti marker kvaliteta, kvantiteta i osetljivosti kosti. Kod mladih žena sa PIJ COLIA1 ne može da ukaže na one žene kod kojih postoji veći rizik za nastanak osteoporoze.Projekat ministarstva br. ON 17305

Finger Length Ratios in Serbian Transsexuals

Atypical prenatal hormone exposure could be a factor in the development of transsexualism. There is evidence that the 2nd and 4th digit ratio (2D : 4D) associates negatively with prenatal testosterone and positively with estrogens. The aim was to assess the difference in 2D : 4D between female to male transsexuals (FMT) and male to female transsexuals (MFT) and controls. We examined 42 MFT, 38 FMT, and 45 control males and 48 control females. Precise measurements were made by X-rays at the ventral surface of both hands from the basal crease of the digit to the tip using vernier calliper. Control male and female patients had larger 2D : 4D of the right hand when compared to the left hand. Control male’s left hand ratio was lower than in control female’s left hand. There was no difference in 2D : 4D between MFT and control males. MFT showed similar 2D : 4D of the right hand with control women indicating possible influencing factor in embryogenesis and consequently finger length changes. FMT showed the lowest 2D : 4D of the left hand when compared to the control males and females. Results of our study go in favour of the biological aetiology of transsexualism

Genetska etiologija prijevremene insuficijencije jajnika

Primary premature ovarian insufficiency (PPOI) is characterized by hypergonadotropic amenorrhea and hypoestrogenism in women under 40 years of age. PPOI incidence is 1:10,000 in women aged 18-25, 1:1000 in women aged 25-30 and 1:100 in women aged 35-40. In 10%-28% of cases, PPOI causes primary and in 4%-18% secondary amenorrhea. The process is a consequence of accelerated oocyte atresia, diminished number of germinated cells, and central nervous system aging. Specific genes are responsible for the control of oocyte number undergoing the ovulation process and the time to cessation of the reproductive function. A positive family history of PPOI is found in 15% of women with PPOI, indicating the existing genetic etiology. Primary POI comprises genetic aberrations linked to chromosome X (monosomy, trisomy, translocation, deletion) or to autosomal chromosome. Secondary POI implies surgical removal of ovaries, chemotherapy and radiotherapy, and infections. Diagnostic criteria include follicle stimulating hormone level >40 IU/L and estradiol level <50 pmol/L.Primarna prijevremena insuficijencija jajnika (PPIJ) je sindrom koji je obilježen hipergonadotropnom amenorejom i hipoestrogenizmom. Incidencija PPIJ je 1:10.000 kod žena starosti 18-25 godina, 1:1000 kod žena starosti 25-30 godina i 1:100 kod žena starosti 35-40 godina. U 10%-28% slučajeva PPIJ je uzrok primarnih, a u 4%-18% sekundarnih amenoreja. Bolest nastaje kao posljedica ubrzanog procesa atrezije oocita, smanjenja broja germinativnih stanica i starenja središnjeg živčanog sustava. Specifični geni su odgovorni za kontrolu broja oocita koji prolaze proces ovulacije i vrijeme prekida reproduktivne funkcije. Pozitivna obiteljska anamneza PPIJ nađena je u oko 15% žena s PPIJ, što ukazuje na postojanje određene genetske etiologije. Primarna insufi cijencija jajnika (PIJ) dijeli se na primarnu i sekundarnu. U primarnu PIJ spadaju genetske aberacije vezane za kromosom X (monosomije, trisomije, translokacije, delecije) ili one vezane za autosomne kromosome. U sekundarnu PIJ spadaju kirurško odstranjenje jajnika, liječenje kemoterapijom i radioterapijom te infekcije. Simptomi su razdražljivost, nemir, gubitak libida, depresija, nesanica, dekoncentracija, napadaji vrućine, povišenje tjelesne težine, suhoća vagine i drugih sluznica. Kriteriji za dijagnozu su folikulostimulirajući hormon viši od 40 IJ/L i estradiol (E2) niži od 50 pmol/L kod žena mlađih od 40 godina

Gaining weight and components of metabolic syndrome in the period of menopause

INTRODUCTION Menopause induces redistribution of fat mass and development of abdominal obesity, increasing risk for metabolic syndrome (MS) by 60%. Related cardiovascular diseases become a leading cause of morbidity and mortality in women after fifty years of age. OBJECTIVE The aim of this study was to investigate the influence of gaining weight on components of MS in the menopause. METHOD The study included 50 obese women, BMI=31.92± 5.83 kg/m2, age 54.40±3.64, time since menopause 5.90±5.46 years, and 37 normal weight women, BMI=23.50±2.13 kg/m2, age 53.92±3.95, time since menopause 5.96±4.92 years. Both groups were divided according to the presence of MS into two subgroups. Anthropometric characteristics and blood pressure were measured. Blood was taken at 8 am for the following: fasting glucose, triglycerides, cholesterol, HDL, LDL, apolipoprotein A (ApoA), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), C-reactive protein (CRP), fibrinogen, FSH, LH, prolactin, oestrogen, progesterone, testosterone and sex hormonebinding globulin (SHBG). RESULTS 66% of obese women had MS compared with 22% normal weight women. Significant differences between groups were found for the following: weight, BMI, waist, hip circumference, waist/hip ratio, diastolic blood pressure, Lp(a), FSH, LH, prolactin (all p&lt;0.01) and fasting glucose (p&lt;0.05). Obese women with and without MS were significantly diverse for the following: waist/hip ratio, systolic blood pressure and fasting glucose (all p&lt;0.01); age, BMI, waist circumference, triglycerides, HDL, Lp(a) and SHBG (all p&lt;0.05). Normal weight women with and without MS had significantly different values of waist/hip ratio, systolic, diastolic blood pressure, triglycerides (all p&lt;0.01); HDL and testosterone (p&lt;0.05). Significant differences were found between obese and normal weight women with MS in anthropometric characteristics, ApoA, Lp(a), fibrinogen (all p&lt;0.01) and FSH (p&lt;0.05). CONCLUSION Abdominal obesity significantly increases incidence of MS as a cluster of cardiovascular risk factors in the menopause

Adrenal incidentaloma in neurofibromatosis type 1

INTRODUCTION Neurofibromatosis type 1 is one of the most common genetically transmitted diseases with a high index of spontaneous mutations and extremely varied and unpredictable clinical manifestations. It is diagnosed by the existence of certain clinical criteria. The presence of numerous localised cutaneous neurofibromas or a plexiform neurofibroma is virtually pathognomonic of neurofibromatosis type 1. The incidence of pheochromocytoma in neurofibromatosis type 1 is 0.1-5.7%. CASE OUTLINE A 56-year old female patient was admitted for further evaluation of incidental adrenal tumour previously diagnosed on computerized tomography (CT). She had previously unrecognized neurofibromatosis type 1 and a clinical picture which could remind of pheochromocytoma. None of the catecholamine samples in 24 hr urine indicated functionally active pheochromocytoma. Chromogranin A was moderately increased. Decision for operation was made after performing the image techniques. Adrenal incidentaloma had features of pheochromocytoma on abdominal magnetic resonance imaging (MRI), with positive 131I-MIBG (iodine 131-labelled metaiodobenzylguanidine scintigraphy). After being treated with phenoxybenzamine and propranolol, she was operated on. The pathohistological finding showed the case of left adrenal pheochromocytoma. CONCLUSION Detailed diagnostic procedure for pheochromocytoma should be performed with patients having neurofibromatosis type 1 and adrenal incidentaloma. Pheochromocytomas are rare tumours with fatal outcome if not duly recognized and cured

Hyperostosis frontalis interna in postmenopausal womenPossible relation to osteoporosis

To improve our understanding of hyperostosis frontalis interna (HFI), we investigated whether HFI was accompanied by changes in the postcranial skeleton. Based on head CT scan analyses, 103 postmenopausal women were divided into controls without HFI and those with HFI, in whom we measured the thickness of frontal, occipital, and parietal bones. Women in the study underwent dual energy x-ray absorptiometry to analyze the bone density of the hip and vertebral region and external geometry of the proximal femora. Additionally, all of the women completed a questionnaire about symptoms and conditions that could be related to HFI. Women with HFI had a significantly higher prevalence of headaches, neurological and psychiatric disorders, and a significantly lower prevalence of having given birth. Increased bone thickness and altered bone structure in women with HFI was localized only on the skull, particularly on the frontal bone, probably due to specific properties of its underlying dura. Bone loss in the postcranial skeleton showed the same pattern in postmenopausal women with HFI as in those without HFI. Recording of HFI in medical records can be helpful in distinguishing whether reported disorders occur as a consequence of HFI or are related to other diseases, but does not appear helpful in identifying women at risk of bone loss

The value of corticotropin-releasing hormone (CRH) test for differential diagnosis of Cushing’s syndrome

Introduction: Diagnosis and differential diagnosis of Cushing’s syndrome (CS) remain considerable challenge in endocrinology. For more than 20 years, CRH has been widely used as differential diagnostic test. Following the CRH administration, the majority of patients with ACTH secreting pituitary adenoma show a significant rise of plasma cortisol and ACTH, whereas those with ectopic ACTH secretion characteristically do not. Objective The aim of our study was to assess the value of CRF test for differential diagnosis of CS using the ROC (receiver operating characteristic) curve method. Method A total of 30 patients with CS verified by pathological examination and postoperative testing were evaluated. CRH test was performed within diagnostic procedures. ACTH secreting pituitary adenoma was found in 18, ectopic ACTH secretion in 3 and cortisol secreting adrenal adenoma in 9 of all patients with CS. Cortisol and ACTH were determined -15, 0, 15, 30, 45, 60, 90 and 120 min. after i.v. administration of 100μg of ovine CRH. Cortisol and ACTH were determined by commercial RIA. Statistical data processing was done by ROC curve analysis. Due to small number, the patients with ectopic ACTH secretion were excluded from test evaluation by ROC curve method. Results In evaluated subgroups, basal cortisol was (1147.3±464.3 vs. 1589.8±296.3 vs. 839.2±405.6 nmol/L); maximal stimulated cortisol (1680.3±735.5 vs. 1749.0±386.6 vs. 906.1±335.0 nmol/L); and maximal increase as a percent of basal cortisol (49.1±36.9 vs. 9.0±7.6 vs. 16.7±37.3 %). Consequently, basal ACTH was (100.9 ±85.0 vs. 138.0±123.7 vs. 4.8±4.3 pg/mL) and maximal stimulated ACTH (203.8 ±160.1 vs. 288.0±189.5 vs. 7.4±9.2 pg/mL). For cortisol, determination area under ROC curve was 0.815±0.083 (CI 95% 0.652-0.978). For cortisol increase cut-off level of 20%, test sensitivity was 83%, with specificity of 78%. For ACTH, determination area under ROC curve was 0.637±0.142 (CI 95% 0.359-0.916). For ACTH increase cut-off level of 30%, test sensitivity was 70%, with specificity of 57%. Conclusion Determination of cortisol and ACTH levels in CRH test remains reliable tool in differential diagnosis of Cushing’s syndrome