Metabolic dysregulation in obese women and the carcinogenesis of gynecological tumors: A review.

Obesity is a significant health issue associated with increased cancer risks, including gynecological malignancies. The worldwide rise in obesity rates is significantly impacting both cancer development and treatment outcomes. Adipose tissue plays a crucial role in metabolism, secreting various substances that can influence cancer formation. In obese individuals, dysfunctional adipose tissue can contribute to cancer development through inflammation, insulin resistance, hormonal changes, and abnormal cholesterol metabolism. Studies have shown a strong correlation between obesity and gynecological cancers, particularly endometrial and breast cancers. Obesity not only increases the risk of developing these cancers but is also associated with poorer outcomes. Additionally, obesity affects the perioperative management of gynecological cancers, requiring specialized care due to increased complications and resistance to therapy. Treatment strategies for managing metabolic dysregulation in patients with gynecological cancers include weight management, statin therapy, and insulin-sensitizing medications. Emerging studies suggest that interventions like intermittent fasting and caloric restriction may enhance the effectiveness of cancer treatments. Furthermore, targeting cholesterol metabolism, such as with statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shows potential in cancer therapy. In conclusion, addressing metabolic issues, particularly obesity, is crucial in preventing and treating gynecological malignancies. Personalized approaches focusing on weight management and metabolic reprogramming may improve outcomes in these patients.

An unusual presentation of hypopituitarism caused by a sellar aneurysm

SUMMARY Hypopituitarism is a rare clinical condition that can present as a partial or complete absence of pituitary hormones. Hypopituitarism is most commonly caused by a sellar or parasellar mass, particularly a tumor, and the gold standard for its differential diagnosis is magnetic resonance imaging (MRI). Intrasellar aneurysm is an unusual cause of hypopituitarism. Indeed, about 0.17% of all cases of hypopituitarism are due to intrasellar aneurysms. We report the case of a 72-year-old man who was admitted to the hospital due to gastrointestinal symptoms and malnourishment. Due to persistent hyponatremia and spontaneous hypoglycemia in laboratory findings, the examination of the hypothalamic-pituitary-adrenal axis was eventually initiated, and the patient was later diagnosed with an unruptured aneurysm of the ophthalmic segment of the right internal carotid artery with sellar extension as a cause of panhypopituitarism. A combined endovascular treatment was performed with stent-assisted coil embolization of the aneurysm, and the patient was prescribed oral hormonal therapy. At the 1-year follow-up visit, no improvement in pituitary function was observed, and a pituitary MRI showed complete aneurysm occlusion and partial empty sella with significantly decreased pituitary volume. Aneurysms of the internal carotid artery are rare and may be associated with hypopituitarism and delayed diagnosis due to their unusual clinical presentation. Endovascular procedures, such as coil embolization of the aneurysm, could be the treatment of choice in these patients. Persistent hypopituitarism may occur even after successful treatment of the aneurysm.

An unusual case of takayasu arteritis presenting as acute myocardial infarction and ischaemic stroke.

Introduction: Takayasu's arteritis (TA) is well-known yet rare disorder, defined as a chronic large vessel vasculitis mainly involving the aorta and its major branches. We present a complex case of a 51-year-old female patient who first presented with acute myocardial infarction as an initial manifestation of Takayasu arteritis, and later with an acute onset of ischemic stroke. Case report: We present a case of 51-year-old female patient who was admitted at the Clinic of Nephrology and Clinical Immunology. During hospitalization, a sudden onset of intense chest pain occurred, followed by a development of heart failure to the level of cardiogenic shock. Electrocardiography showed signs of ST-elevated myocardial infarction (STEMI) of the anterior wall, and an increase in cardiospecific enzymes. CT angiography indicated an occlusion of the left common carotid artery (ACC), subclavian and axillary arteries as well as a penetrating aortic ulcer localized infrarenal. In the further course of treatment, left-sided weakness of the body was registered. Head CT scan showed an acute ischemic lesion high parietal on the right, as well as a chronic ischemic lesion on the front right. Doppler ultrasonography of carotid and vertebral arteries registered left occlusion, right ACC/external carotid artery (ACE) stenosis with suspected "macaroni sign". Final diagnosis of Takayasu arteritis was established and corticosteroids were included in the therapy (primarily in pulse doses) with the first pulse of cyclophosphamide of 1000mg. Conclusion: This disease should be considered in female patients who present with chronic inflammation and acute coronary syndrome.

Potential influence of the phthalates on normal liver function and cardiometabolic risk in males.

Phthalates are ubiquitous environmental contaminants, massively used in industry as plasticizers and additives in cosmetics, which may impair the human endocrine system inducing fertility problems, respiratory diseases, obesity, and neuropsychological disorders. The aim of this study was to examine the influence of the monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) on the liver function and cardiometabolic risk factors in males. In this research, 102 male participants (51 normal weight and 51 overweight/obese) were enrolled and examined for phthalate metabolites exposure in urine samples after 12 h of fasting. MEP was found in 28.43% (29/102) volunteers, while MEHP was detected among 20.59% (21/102) participants. Statistically significant increment in transaminase serum levels was observed in MEP-positive normal weight subgroup. Linear correlation was obtained between MEP concentration in urine samples and triglyceride (TG) serum levels (r 2 = 0.33; p < 0.01), visceral adiposity index (VAI) (r 2 = 0.41; p < 0.01), lipid accumulation product (LAP) (r 2 = 0.32; p < 0.01), and TG to high-density lipoprotein (HDL) ratio (r 2 = 0.40, p < 0.01) among the obese. The MEHP-positive normal weight volunteers had statistically significant increment of body mass index (p = 0.03) compared to MEHP-negative participants. Urine MEHP concentrations were negatively correlated with HDL serum levels (r 2 = 0.31; p < 0.05) in the normal weight subgroup. The phthalates exposure may be related to statistically significant ALT and AST serum levels increment as well as with increased BMI, while the phthalate levels in the urine may be correlated with increased TG and decreased HDL cholesterol serum levels and associated with indicators of cardiometabolic risk and insulin resistance as LAP and VAI.

The Wnt/ß-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity.

BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/ß-catenin signalling pathway (WßcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WßcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS: The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS: Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION: CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the metabolic syndrome parameters? Pilot study.

The study objective was to determine if the healthy participants were exposed to diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this exposure could be linked to the development of metabolic syndrome. The study included 103 healthy volunteers of similar age with normal BMI values, waist circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were measured in the morning urine samples to detect monoethyl phthalate (MEP) and mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were formed. Both MEP group and control group had similar results. The correlations between MEP and the measured parameters were insignificant. The correlation between the MEHP group and the age was significantly negative, but between the MHEP group and the waist circumference the correlation was significantly positive. Lipids and lipoproteins were within the reference values and equal in both groups. The significant negative correlation was observed only between MEHP and HDL. Our population is exposed to DEP and DEHP. There was only a significant correlation between DEHP and the observed metabolic syndrome components. Its negative impact was higher as the participants were younger.

Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet--a case report.

INTRODUCTION: Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. CASE REPORT: We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 µg of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. CONCLUSION: Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.

Risk factors for accelerated atherosclerosis in young women with hyperprolactinemia.

Prolactin is a metabolic hormone. The hypothesis is that hyperprolactinemia can cause metabolic and inflammatory changes which are associated with accelerated atherosclerotic process, but the treatment of hyperprolactinemia with dopamine agonists, leads to reversibility of these processes. The first aim of this study was to determine whether hyperprolactinemia in premenopausal women is accompanied with the increase in body mass index (BMI), changes in body composition, lipid disturbances, the presence of inflammation and changes in systolic and diastolic blood pressure as risk factors for the development of early atherosclerosis. The second aim was to know whether the therapy of hyperprolactinemia and prolactin normalization lead to improvement of the observed parameters. Twenty female patients with prolactinomas, before and during treatment with dopamine agonists and 16 healthy controls were evaluated. Prolactin, BMI, total body fat, free fat mass, total body water, total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and fibrinogen as well as systolic and diastolic blood pressure were measured at baseline and during the therapy. Hyperprolactinemic patients had pathologic and significantly higher levels of prolactin (PRL) than the controls (p=0.000). The BMI, body fat, total body water (TBW), total cholesterol, triglycerides, LDL were in normal range and higher in the patients than in the controls. HDL was lower in hyperprolactinemic females than controls. The difference was significant only for body fat (fat % p=0.006; fat kg p=0.009). Fibrinogen was slightly increased in patients compared with the controls. Hyperprolactinemic patients had normal, but increased levels of systolic and diastolic blood pressure compared with the controls. The difference with border significance was found in diastolic blood pressure (p=0.065). The correlation of PRL with all the observed parameters was positive apart from HDL, but relatively significant only with diastolic blood pressure (r=0.31). The therapy with dopamine agonists caused the decrease of all the observed parameters, but significant decreases was achieved only in BMI (p=0.028), total cholesterol levels (p<0.001) and LDL (p<0.002). Changes in BMI, body composition, serum lipids and lipoproteins, fibrinogen level and blood pressure confirm our hypothesis about the possible role of hyperprolactinemia in developing adverse metabolic disturbances which are reversible after treatment.

Dental extractions and risk of bleeding in patients taking single and dual antiplatelet treatment.

Our aim was to evaluate the effects of single and dual antiplatelet treatment on postoperative bleeding in patients having dental extractions. The prospective clinical study included 160 patients who were taking antiplatelet drugs. The first group (n=43) were taking 2 drugs, mostly aspirin and clopidogrel, and the second group (n=117) were taking a single antiplatelet drug in the form of aspirin (n=84), clopidogrel (n=20), and ticlopidine (n=13). All patients had simple dental extractions, and local haemostasis was with resorbable collagen sponges, without suturing of the wound. The control group comprised 105 healthy subjects with a similar number of dental extractions. Bleeding was an "event" if it continued for more than 12h, made the patient call or return to the dental practice or emergency department, induced a large haematoma or ecchymosis within the oral soft tissues, or required blood transfusion. A total of 110 teeth were extracted on 59 occasions in the dual drug group, and 232 teeth on 128 occasions in the single drug group. Bleeding was recorded after extraction in only one patient on dual aspirin-clopidogrel treatment, which was mild and easily controlled by local haemostasis. The incidence of postoperative bleeding did not differ significantly among the three groups (χ(2)=4.3, p=0.11). However, the wound was sutured to achieve effective initial local haemostasis in 4/59 (6.8%) and 2/128 (1.6%) occasions of tooth extractions in the dual and single drug groups, respectively, and none in the control group (χ(2)=10.02, p=0.007). Patients taking single or dual antiplatelet drugs may have teeth extracted safely without interruption of treatment using only local haemostatic measures.

Effects of phthalic acid esters on fetal health.

INTRODUCTION: Phthalates are synthetic industrial compounds capable of disrupting endocrine system. Effects of phthalates depend on dosage, duration of action and stage of development of the individual, thus making the fetus, newborn, and children at puberty the most vulnerable groups. METABOLISM OF PHTHALATES: Metabolism of these compounds consists of at least two steps: hydrolysis and conjugation. They are mainly excreted in urine, with a low percent being excreted through feces. EXPOSURE TO PHTHALATES: Exposure to the effects of phthalates begins at the intrauterine stage since the phthalates pass through the placental barrier. Phthalates may be found in plastic products, toys, medical equipment, industrial materials, food, and clothes. DETERMINATION OF PHTHALATE LEVELS IN HUMANS: Urine is the best sample for evaluating phthalate levels in humans because of rapid phthalate metabolism and high concentrations of metabolites in the urine. FETAL TESTICULAR DYSGENESIS SYNDROME: Fetal testicular dysgenesis syndrome involves disorders of male genital tract such as shortened anogenital distance, hypospadia, cryptorchidism, malformations of seminal vesicles, prostate, epididymis and it results from the harmful effects of phthalates. OTHER EFFECTS OF PHTHALATES ON HEALTH: Negative effects of phthalates on female health are mostly reflected in anovulation, premature puberty, changes in duration of pregnancy. There is a possible effect on neurocognitive development, occurrence of allergies, asthma, testicular carcinoma, hepatic and renal damages, insulin resistance and obesity, thyroid dysfunction. CONCLUSION: Further studies are needed to establish the safe phthalate concentration in certain products and to determine more negative consequences of exposure to phthalate.

The effects of combined oral anticoagulant-aspirin therapy in patients undergoing tooth extractions: a prospective study.

BACKGROUND: The authors conducted a study to evaluate the effect of combined oral anticoagulant-aspirin therapy on postoperative bleeding in patients undergoing tooth extractions. METHODS: A total of 213 patients were divided into three groups of 71 participants each. Patients in group A received combined anticoagulant-aspirin (100-milligram prophylactic dose) therapy. Patients in group B received oral anticoagulant therapy. Patients in group C received aspirin therapy (100-mg prophylactic dose). Bleeding was marked as an "event" if it met the following criteria: the bleeding continued beyond 12 hours, patient had to call the surgeon or return to dental practice or emergency department, bleeding resolved with large hematoma or ecchymosis within the oral soft tissues, or required a blood transfusion. RESULTS: Mean international normalized ratio (INR) (standard deviation) was 2.43 (0.61) in group A, and 2.45 (0.60) in group B. Postoperative bleeding occurred in three (4.2 percent) participants in group A, two (2.8 percent) participants in group B and no (0.0 percent) participants in group C. The authors found no statistical significance in postoperative bleeding between these three groups (χ(2) = 2.867, P = .238). All cases of hemorrhage were controlled easily by using local hemostatic measures. CONCLUSION: Tooth extractions can be performed safely while patients continue to receive combined anticoagulant-aspirin therapy. CLINICAL IMPLICATIONS: In patients receiving combined anticoagulant-aspirin therapy, simple tooth extractions can be performed safely without discontinuing either oral anticoagulant or antiplatelet therapy if their INRs are within therapeutic range and appropriate local hemostasis measures are provided.

[Iodine and thyroid gland with or without nuclear catastrophe].

INTRODUCTION: Iodine, as a trace element, is a necessary and limiting substrate for thyroid gland hormone synthesis. It is an essential element that enables the thyroid gland to produce thyroid hormones thyroxine (T4) and triiodothyronine (T3). Synthesis of Thyroid Hormones and Iodine Metabolism. Three iodine molecules are added to make triiodothyronine, and four for thyroxine - the two key hormones produced by the thyroid gland. Iodine deficiency The proper daily amount of iodine is required for optimal thyroid function. Iodine deficiency can cause hypothyroidism, developmental brain disorders and goiter. Iodine deficiency is the single most common cause of preventable mental retardation and brain damage in the world. It also decreases child survival, causes goiters, and impairs growth and development. Iodine deficiency disorders in pregnant women cause miscarriages, stillbirths, and other complications. Children with iodine deficiency disorders can grow up stunted, apathetic, mentally retarded, and incapable of normal movements, speech or hearing. Excessive Iodine Intake. Excessive iodine intake, which can trigger a utoimmune thyroid disease and dysfunction. is on the other side. Iodine use in Case of Nuclear Catastrophe. In addition to other severe consuquences of radioactivity, high amount of radioactive iodine causes significant increase in incidence of thyroid gland carcinoma after some of the nuclear catastrophes (Hiroshima, Nagasaki, Chernobyl, Fukushima). The incidence of thyroid carcinoma was increased mostly in children. This paper was aimed at clarifying some of the possibilities of prevention according to the recommendations given by the World Health Organization.

Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1.

BACKGROUND/AIM: Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. METHODS: The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). RESULTS: The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). CONCLUSION: The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

[Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

INTRODUCTION: Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. CONCLUSIONS: Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

[The role of insulin analogues in the current treatment of diabetes mellitus].

INTRODUCTION: Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion. NORMAL INSULIN SECRETION: In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis) and stimulated (as a response to a meal). Conventional insulin preparations--human insulin, have time-action profiles that cannot fully immitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. RAPID-ACTING ANALOGUES: Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analogues, lispro and aspart are available. BASAL INSULIN ANALOGUES: The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day), and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action. MITOGENIC INFLUENCE: The mitogenic influence of insulin is due to the affinity to bind to IGF-I receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals. CONCLUSION: In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as metabolic parameters, it has been proven that only strict glycemic control can lower the risk of developing complications. Discovery of insulin analogues (both rapid acting and basal) enables physicians to provide better glycoregulation and less hypoglycemic incidents to their patients.