Insulin resistance – the basics every medical specialist should know

Introduction and purpose: Insulin resistance (IR) is a health problem as it can accompany obesity and lead to serious metabolic complications. In recent years, it has been "overdiagnosed" in clinical practice due to the lack of specific diagnostic criteria. The article summarizes the current knowledge in the field of pathophysiology, clinical picture and diagnostics. State of knowledge: Obesity remains the leading cause of IR, especially in the 21st century. In a positive energy balance, the adipocyte overloaded with fat protects itself against further influx of glucose and fats and becomes insulin insensitive. A component of IR development is subclinical inflammation of macrophage-rich adipose tissue which is exacerbated by an adipocytokine imbalance, which in turn generates IR. The markers of cellular resistance to insulin are free fatty acids in the bloodstream which are responsible for the lipotoxicity in hepatocytes and myocytes. Compensatory fasting hyperinsulinemia, which is currently considered the most sensitive diagnostic criterion, provides evidence of IR. An effective method of sensitizing cells to insulin is lifestyle modification, including a low-energy diet with regular physical activity in the form of aerobic-resistance exercise. Literature recommends no pharmacological treatment of IR alone, without obesity or other concomitant diseases. Conclusions: IR is not a separate disease, but only a pathological expression of cells' adaptation to excess of consumed energy. However, in its systemic form, when the protective mechanisms become ineffective, it induces metabolic disturbances. Only the causal treatment of IR guarantees therapeutic success

Is water fluoridation correlated with hypothyroidism?

Introduction: Hypothyroidism is a global health problem. Primary thyroid hormone deficiency may be caused by a wide spectrum of health problems, e.g. chronic autoimmune thyroiditis, postpartum thyroiditis, iodine deficiency, thyroid or parathyroid surgery and drugs. In recent years, scientific studies have also been published indicating a correlation between excessive intake of fluoride and hypothyroidism. Fluoride is added to the water sources of many countries. Objective: The purpose of the study was to review and compare currently available data on PubMed about fluoride-induced hypothyroidism. A brief description of the state of knowledge: Evidence based knowledge suggests that there is a potential relationship between water fluoridation and endocrine system disorders, especially hypothyroidism. Current studies indicate that TSH hormone levels get elevated with increased fluoride intake. The reason is supposed to be that fluorine is more electronegative than iodine and therefore easily displaces iodine from the body, thus affecting thyroid function. Conclusions: Current studies do not clearly show a simple correlation between excessive fluoridation of drinking water and the occurrence of hypothyroidism. However, inconclusive scientific evidence and the prevalence of hypothyroidism in the population indicate the need for further research in this area

Thyrotropinoma - the case report about one of the rarest type of pituitary adenomas

Pituitary tumours are a significant diagnostic problem in clinical practice. Considering all the rarity of thyrotropic hormone secreting adenoma it is a diagnostic and therapeutic challenge in part due to the lack of the preoperative standards. TSH-oma, besides hyperthyroidism symptoms, might be a cause of other endocrine disorders, most often dysfunction of other tropic axes and may cause neurological symptoms associated with sella expansion. We report a case of a 49-year-old male patient with macroadenoma, overt clinical hyperthyroidism, secondary adrenal insufficiency and hypogonadotropic hypogonadism. The diagnosis of thyrotropinoma was confirmed by blood tests that revealed elevated FT3 and FT4 levels together with high TSH. Thyrotropin-releasing hormone (TRH) test was performed and  magnetic resonance imaging (MRI) imaging revealed the presence of macroadenoma. Histopathology examination confirmed the diagnosis of thyrotropic cell pituitary adenoma. The appropriate therapy for thyrotropin pituitary adenoma has not been elaborated in reports of this domain. Preoperatively the patient was prepared by long-acting somatostatin analogue (Sandostatin LAR) injections to reduce tumor size with good therapeutic effect afterwards underwent surgical transsphenoidal treatment successfully. However, specific treatment guidelines for pituitary thyrotropic tumors need to be elaborated more in details

Portal vein thrombosis and non-compliance in a high risk patient – a case study

Portal vein thrombosis is a pathological process that refers to the obstruction of blood flow secondary to thrombus formation. It may be caused by a variety of conditions including cancer, cirrhosis, myeloproliferative neoplasms (eg. polycythemia vera) or surgery in the area of the portal vein (eg. splenectomy). Recent studies suggest that patients with a positive history of SARS-CoV-2 infection have a higher risk of thromboembolic incidents. According to current procedures patients with increased thromboembolic risk should receive anticoagulants. Non-compliance to medical recommendations may develop a disease, directly threatening the patient's health and life. We present a case report of a 69 year old woman with a history of polycythemia vera, recent splenectomy, and SARS-CoV-2 infection who developed massive portal vein thrombosis two days after discontinuation of enoxaparin

Polypharmacotherapy with anti-obesity drugs - case report

Obesity is a chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse health consequences. It is diagnosed based on body mass index and waist circumference. In case of severe obesity, bariatric surgery or pharmacotherapy is recommended. We present a case report of a 28 years old man with class III obesity (77,6 kg/m2). In order to qualify the patient for bariatric surgery, a decision to combine two anti-obesity medications has been made. This kind of obesity management is neither recommended, not contraindicated, but has shown good effects on body mass reduction. This case report should initiate the discussion about recommendations modification towards combining anti-obesity medications of different mechanisms of action

Graves-Basedow disease treated by complementary medicine leading to severe thyrotoxicosis – a case report

Graves' disease is a common cause of hyperthyroidism. Inadequate treatment or non-compliance can lead to serious complications, including thyroid storm.  We present the case of a 22-year-old woman who had been treated with antithyroid drugs (ATD) for almost 7 years, however decided to suspend conventional treatment and turned towards complementary and alternative medicine methods. Following the bioenergotherapist's advice, she began taking Lugol’s solution (LS) at a dose of 30 drops per day. After about one month of such therapy, the patient was urgently admitted to the Emergency Department with thyrotoxicosis with a high risk of thyroid storm development. With the implementation of intensive thyrostatic treatment and steroid therapy, euthyroidism was successfully restored

The role of chemokines in liver disease

Chemokines are involved in many processes, including the normal immune response to infection, as well as pathological processes such as carcinogenesis, autoimmunity and inappropriate inflammatory responses. These processes represent an important aspect in the context of liver disease, its progression and the possibility of inhibiting fibrosis. Chemokines belong to low molecular weight proteins with a wide range of functions affecting cell migration, involving different physiological and pathological processes. Depending on whether they participate in the maintenance of homeostasis during periods of well-being or represent a type of intervention of the organism to its disorders, their secretion by cells is constitutive or induced. This article focuses on the classification, structure and functions of these molecules and their possible involvement in the pathogenesis of liver diseases, as well as the possibilities of therapeutic application of this knowledge

Colonic contained perforation of unknown etiology treated conservatively in a 34 year old female patient: a case report

A colon perforation is defined as a disruption in the continuity of the gastrointestinal wall. A contained perforation is a situation where the perforation is self-limited, usually by adhesion to other structures in the abdominal cavity. Many conditions can cause perforation, including cancer, diverticular disease, or iatrogenic perforation such as during an endoscopy procedure. Less commonly, the cause may be inflammatory bowel disease or the presence of a foreign body in gastrointestinal tract. Furthermore, there are also publications describing situations of spontaneous rupture of the intestinal wall, i.e. spontaneous perforations. This group includes spontaneous perforation caused by fecal stones and idiopathic perforation. In this article we present a case report of a 34 year old woman with perforation of the large intestine without any apparent cause. We discuss the differential diagnosis of patients with conservatively treated perforation with unknown colonoscopy result

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2

Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation

Obesity in perimenopause — current treatment options based on pathogenetic factors

The health of post-menopausal women has become of paramount concern due to the aging of the world’s population. Concurrently, the prevalence of obesity among postmenopausal women is expected to increase, presenting a significant public health challenge. Although weight gain during menopause is a well-observed phenomenon, its underlying causes and mechanisms remain incompletely understood. This manuscript reviews the literature to explore potential hormonal factors and pathomechanisms contributing to obesity during perimenopause, aiming to identify pathogenic factors that can guide treatment selection. Menopause-induced hormonal changes, including hypoestrogenaemia, hypergonadotropinaemia, relative hyperandrogenaemia, growth hormone deficiency, leptin resistance, and chronic stress affecting the hypothalamic-pituitary-adrenal axis, have been implicated in the onset of obesity in perimenopausal women. These hormonal fluctuations, alongside lowered daily energy expenditure, lead to metabolic alterations that elevate the risk of developing metabolic disorders and cardiovascular diseases. Weight gain in perimenopausal women is associated with higher total and abdominal adipose tissue and lower lean body mass. Addressing this issue requires individualized behavioural management, supported by effective pharmacological therapy, and, when warranted, complemented by bariatric surgery. Modern obesity treatment therapies have demonstrated safety and efficacy in clinical trials, offering the potential to reduce excess body fat, improve metabolic profiles, lower cardiovascular risk, and enhance the quality and longevity of women’s lives. In addition to standard obesity therapies, the article examines different treatment strategies based on obesity’s pathogenic factors, which may offer promising options for treating obesity with or without complications in perimenopausal women. One such potential approach is menopausal hormone therapy (MHT), which hypothetically targets visceral obesity by reducing visceral adipose tissue accumulation, preserving metabolically active lean body mass, and improving lipid profiles. However, despite these reported benefits, gynaecological and endocrinological societies currently do not recommend the use of MHT for obesity prevention or treatment, necessitating further research for validation. Emerging evidence suggests that visceral obesity could result from hypoestrogenaemia during perimenopause, potentially justifying the use of MHT as a causal treatment. This highlights the importance of advancing research efforts to unravel the intricate hormonal and metabolic changes that occur during perimenopauseand their role in obesity development