Browsing by Author "Marina, Ljiljana (36523361900)"

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised. © 2023 by the authors.

Estradiol promotes neuronal growth, transmission, survival, myelinization, plasticity, synaptogenesis, and dendritic branching and it improves cognitive function. Alzheimer’s disease (AD) is characterized by amyloid plaques, neurofibrillary tangles, and the loss of neuronal connection in the brain. Genomic analysis has concluded that hypoestrogenism influences the APOE gene and increases the risk of AD. Premature ovarian insufficiency (POI) is defined as oligo/amenorrhea in women below 40 years of age, low estradiol, and high-gonadotropin levels. Early symptoms and signs of POI must be detected in time in order to prevent subsequent complications, such as Alzheimer’s disease. Meta-analysis has shown favorable effects of estrogen in preventing Alzheimer’s. We measured some of the typical markers of AD in women with POI such as interleukin 6 (IL-6), interleukin 8 (IL-8), tissue necrosis factor α (TNFα), TAU1, TREM2, and amyloid precursor proteins (APP). While FSH, LH, and IL-8 were significantly higher in POI group, compared to controls, testosterone and DHEAS were lower. A significant decrease in IL-6 was found in the POI group during a 6-month therapy, as well as an increase in amyloid precursor proteins. CONCLUSION: Neurological complications of POI, such as declining short-term memory, cognitive function, and dementia, have to be promptly stopped by initiating estro-progestogen therapy in POI. A long-term continuation of the therapy would be strongly advised. © 2023 by the authors.

This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated. © 2021, The Author(s).

This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated. © 2021, The Author(s).

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, Chi-square 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.

Objective: To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). Design: Systematic review and meta-analysis. Methods: Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). Results: In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. Conclusions: The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities. © 2023 BioScientifica Ltd.. All rights reserved.

Objective: To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). Design: Systematic review and meta-analysis. Methods: Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). Results: In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. Conclusions: The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities. © 2023 BioScientifica Ltd.. All rights reserved.

More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10–15 IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10–15 IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3–6 month before pregnancy. (3) TSH has to be 1–2.5 mM/L during 3–6 months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women’s acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10–15 IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10–15 IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3–6 month before pregnancy. (3) TSH has to be 1–2.5 mM/L during 3–6 months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women’s acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 μg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 μg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion"(MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-Adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future. © 2023 The Author(s). Published by Oxford University Press on behalf of European Society of Endocrinology.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 μg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 μg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion"(MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-Adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future. © 2023 The Author(s). Published by Oxford University Press on behalf of European Society of Endocrinology.

Introduction/Objective Hot flashes are one of the first clinical symptoms of menopause. The mechanism of hot flashes is still not fully understood. Changes in concentrations of the circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and other hormones can lead to thermoregulatory dysfunction. The aim of this study was to examine the association between dynamic changes in concentrations of sex hormones and the presence of vasomotor symptoms in menopausal women. Methods The study involved 36 women divided into two groups: in the first group there were 24 women with hot flashes, BMI 26.16 ± 3.42 kg/m2; the control group comprised 12 women, BMI 26.82 ± 3.89 kg/m2. Data on the presence of hot flashes were based on medical history data. Venous blood samples were collected for the analyses of FSH, LH, prolactin, estradiol, progesterone, testosterone, sex hormone binding globulin, dehidroepiandrosteron sulfate, thyroid-stimulating hormone, and thyroxin. During the subjective feeling of hot flashes, three blood samples during the day and night were collected to determine the mean levels of FSH, LH, and estradiol in women with hot flashes. Results Women with hot flashes had significantly higher prolactin (389.58 ± 123.69 mIU/L to 258.19 ± 122 mIU/L, p < 0.01) and dehydroepiandrosterone sulfate (3.60 ± 2.49 nmol/L vs. 1.88 ± 1.27 nmol/L, p < 0.05) levels, as well as lower mean values of FSH during hot flashes during the day (69.08 ± 28.84 IU/L vs. 107.18 ± 39.11 IU/L, p < 0.01) and night (60.72 ± 21.89 IU/L vs. 104.57 ± 38.06 IU/L, p < 0.01). Conclusion Women with hot flashes had significantly lower mean FSH levels during hot flashes during the day and night than the control group. © 2018, Serbia Medical Society. All rights reserved.

In the ancient Rome, average life duration was 23 years; in Sweden at the end of the eighteenth century, 36.6 years for women and 33.7 for men; and in many European countries at the beginning of the twenty-first century, life expectancy was 72 and 76 years, respectively. The menopause (period in women’s life 1 year after the last menstruation until the end of life) and involutive hypoandrogenism in males (testosterone below 12 nmol/L and typical symptoms) are characterized by decrease of gonadal steroids and initiating of cardiovascular diseases (CVD). Rahman [1] found that women who entered early menopause (40–45 years) had 40% increase of heart disease. Meta-analysis confirmed these data (Table 16.1). © 2018, International Society of Gynecological Endocrinology.

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin,TSH, prolactin, testosterone), karyotype (>30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications.Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

Genetic and environmental factors influence the quality of life and well-being. Breaking of adaptive mechanisms, induced by stressors, triggers diseases. Premature ovarian insufficiency (POI) is characterized by oligo/amenorrhea, high gonadotropin, and low estradiol levels in women younger than 40 years of age. Known etiological factors inducing POI include chromosomal abnormalities, enzyme changes, autoimmune diseases, FSH receptor gene polymorphism, inhibin B mutation, infectious disease, adnexectomy, radiotherapy, uterine artery embolization, etc. Unknown factors include stressors, inflammation, telomerase shortening, biological clock acceleration, etc. Early POI symptoms, significantly decreasing the quality of life, are hot flushes, irritability, anxiety, depression, mood swings, loss of concentration, insomnia, loss of libido, etc. Late complications include cardiovascular diseases, osteoporosis, metabolic syndrome, cognitive changes, Alzheimer’s disease, urogenital dysfunction, decreased fertility rate, etc. Diagnosis is confirmed by FSH >40 IU/L (or 25 IU/L), estradiol <50 pmol/L, and oligo/amenorrhea in women younger than 40 years of age. Also, suggested analyses are AMH, inhibin B, prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, free thyroxin (fT4), thyroid-stimulating hormone (TSH), cortisol, vitamin D, and oral glucose tolerance test (OGTT). Visualization methods include ultrasound examination of uterus, ovaries, and breasts and osteodensitometry. In untreated POI patients, mortality rate is increased. Therapy with estroprogestogens, and all other insufficient hormones (testosterone, fT4, DHEAS, vitamin D, etc.), has to be initiated immediately and continued without age limits, depending on individual needs, in order to achieve the best quality of life. © 2023, International Society of Gynecological Endocrinology.

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.

Background/Aim. In menopausal women lipid and lipoprotein values are important predictors of development of cardiovascular diseases (CVD). The use of estrogens reduces levels of low density lipoprotein cholesterol (LDL-C) and lipoprotein A [Lp(a)], and increases levels of triglycerides (TG) and high density lipoprotein cholesterol (HDL-C) depending on the dose and route of administration. Simultaneous administration of progesterone, depending on the type, can have different effects on lipids. The aim of the study was to examine the effect of estroprogestagen therapy on the lipid metabolism of women in menopause, depending on the administration route. Methods. A study was conducted as prospective clinical interventional study with controlled parallel groups. It included 64 women in menopause, divided into three groups: the group 1 (n = 22) on oral therapy with estroprogestagens, the group 2 (n = 17) on transdermal patch therapy with estroprogestagens and the group 3 (n = 25) treated with estroprogestagens given intramuscularly. The following biochemical parameters in the serum were determined: total cholesterol (TC), HDL-C, LDL-C, TG, Lp(a), apoprotein A (Apo-A), apoprotein B (Apo-B), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-SO4), prolactin and thyroid-stimulating hormone (TSH), prior to administration of the menopausal hormonal therapy (MHT), as well as after sixth months and 2–5 years from the beginning of the therapy. The statistical significance of the difference in values obtained was examined independently and depending on the route of MHT application. Results. MHT, regardless of the administration route, led to a statistically significant continuous decrease of TC, LDL-C and Apo-B levels and the continuous increase of HDL-C and Apo-A levels. Serum levels of TC, LDL-C, HDL-C, Lp(a), Apo-A and Apo-B did not show a statistically significant differences among groups of women given MHT by different routes. It was found that the serum level of Apo-A increased significantly with the rise of estradiol, and the values of LDL and Apo-B decreased regardless of the route of the MHT application. Conclusion. MHT introduced in time, regardless of the route of administration, has beneficial effects on the lipid status of menopausal women and consequently might prevent numerous cardiovascular diseases that are the leading cause of mortality. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

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. © 2018, Klinicka Bolnica Sestre Milosrdnice. All rights reserved.

Main regulators of breast metabolism are estradiol, progesterone, prolactin, growth hormone, and insulin-like growth factor 1 (IGF-1) [1]. They control cell function, proliferation, and differentiation activating intracellular signaling cascade (Erk, Akt, JNK, and Ark/Stat) of breast tissue [2]. Estrogen receptor (ER) expression in the breast is stable and differs relatively little in correlation with reproductive status, menstrual cycle phase, or exogenous hormones [3]. Estrogens have apocrine, paracrine, and intercrine effects. Receptors for estradiol are present in fibroblast, epithelial cells, adipocytes, and stromal tissue. Intramammary concentration of estradiol is 20 times higher compared to the level in the blood. Estradiol increases number of progesterone receptors, epithelial proliferation in the luteal phase, galactophore differentiation, connective tissue development, and growth hormone. © 2021, International Society of Gynecological Endocrinology.

Background: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. Methods: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. Findings: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2–23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9–82·0] vs 64·0% [61·4–66.4]) while maintaining sensitivity (99·0% [94·4–100·0] vs 100·0% [96·3–100·0]; PPV 19·7%, 16·3–23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6–41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2–84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4–100·0). Interpretation: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. Funding: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license