Endocrine regulations最新文献

Objective. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare, but potentially life-threatening cause of Cushing's syndrome. Its clinical recognition may be delayed, especially when classical features of hypercortisolism are absent. We present two cases, in which hypokalemic metabolic alkalosis was the initial and main clinical clue leading to the diagnosis of neuroendocrine carcinoma with ectopic ACTH production. Case 1. The first case was a 71-year-old woman admitted with progressive weakness, gait disturbance, and uncontrolled hypertension. Laboratory tests revealed severe hypokalemia and metabolic alkalosis. Endocrine evaluation showed markedly elevated urinary free cortisol and plasma ACTH, with absent suppression on low-dose dexamethasone testing. Colonoscopy for anemia revealed a rectal mass and histopathology confirmed poorly differentiated neuroendocrine carcinoma. Imaging demonstrated widespread metastases. Despite supportive treatment, she died of multi-organ failure during hospitalization. Case 2. The second case was a 67-year-old woman presenting with fatigue, weakness, and weight loss. Laboratory findings included hypokalemia, metabolic alkalosis, renal dysfunction, and elevated liver enzymes. Hormonal studies again confirmed ACTH-dependent Cushing's syndrome without suppression on dexamethasone testing. Imaging revealed a right hilar lung mass and bronchoscopy with biopsy confirmed small-cell neuroendocrine carcinoma. PET-CT showed disseminated metastases. Although chemotherapy was initiated, she developed rapid progression and died shortly thereafter. Conclusion. These cases highlight that severe hypokalemic metabolic alkalosis may represent the primary manifestation of ectopic ACTH syndrome even in the absence of overt Cushingoid features. Recognition of this biochemical pattern should prompt consideration of neuroendocrine tumors allowing earlier diagnosis and timely therapeutic intervention in this aggressive condition.

Objective. Involvement of various endocrine disruptors (EDs) in pathophysiology of reproductive system disorders has been suggested previously. The studies have shown adverse effects of the individual substances, however, in the real-life situation, numerous chemicals enter the organism on a daily basis. This points to the importance of examination of the combined effects of exogenous chemicals on biological systems, including reproductive system. The ovaries are a target of different EDs, which may impact the processes within the ovarian follicles. The aim of the present study was to examine the effects of binary or ternary mixtures combining selected nonpersistent disruptors: bisphenol A (BPA), BPA-dimethacrylate (BPADM), benzyl butyl phthalate (BBP), 4-chloro-3-methylphenol (CMP), or alkylphenols (4-octylphenol, OP; 4-nonylphenol, NP; and tert-octylphenol, TOP) on ovarian follicular cell functions. Methods. Porcine oocyte-cumulus complexes (OCCs) and granulosa cells (GCs) were treated with the tested ED mixtures (BPA+BBP, CMP+BBP, BPA+BPADM, BPA+BBP+CMP, and OP+NP+TOP) in a wide concentration range from 10-10 to 10-4 M. Follicle-stimulating hormone (FSH)-induced cumulus expansion was assessed after 24 h of culture according to a subjective scoring system. After 44-h treatment, oocyte nuclear maturation was evaluated. Basal and FSHstimulated progesterone production by OCCs and GCs was measured by commercial radioimmunoassay after 44 h and 72 h of the culture, respectively. One-way ANOVA and Bonferroni post-test were used for statistical analysis of data. Results. The results obtained showed that the lower concentrations of ED mixtures (10^-10- 10^-6 M) did not exert significant changes, while the highest concentration (10-4 M) significantly inhibited cumulus expansion, oocyte meiotic maturation, and progesterone production by OCCs and GCs. Moreover, the inhibitory effects of ED mixtures seem to be more profound than the effects caused by the individual substances. Conclusion. The experimental approach of testing mixtures should provide a more comprehensive view on the effects of the ubiquitous EDs on various cell types of the reproductive organs.

Objective. Symptoms of thyroid defects involve sleep disorders, gain or loss of weight, tremors of hand, constipation, dry skin, bradycardia, diarrhea, irregular menses, and hot or cold tolerance. Workers in different professions face different situations that can lead to stress. This study aimed to examine the association between shift work (office or irregular) and thyroid function indicators, interleukin-37 (IL-37) levels, and development of chronic diseases (cardiovascular, diabetes). Methods. The current study comprised three groups: 1) office staff, 2) irregular staff (comprising different jobs), and 3) controls (not working subjects). Eighty-five subjects, aged 30-55 years, were included in the study. Body mass index (BMI) was calculated for each participant. Venous blood was collected and serum levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase (TPO) were determined by electrochemiluminescence (ECL) analysis using an automatic immunochemical analyzer Cobas E 411 (Roche Diagnostics, Germany). Serum IL-37 levels were measured using ELISA kit. Results. Serum T3 (p<0.01) and T4 (p<0.001) levels were significantly decreased in both office and irregular shift work groups compared to the controls. The mean T3 levels were higher in subjects with irregular shift work (1.162±0.11 ng/mL) compared to subjects with office shift work (1.14±0.12 ng/mL). Significantly increased TSH and TPO serum levels (p<0.01) were found in both the irregular shift work and office shift work groups compared to the control group. Similarly, IL37 levels were significantly increased in office shift work (294.8±21.05 ng/mL) and irregular shift work subjects (278.0±16.22 ng/mL) (p<0.001) compared to controls (56.5±0.28 ng/mL). Cardiac disease (p<0.01), hypertension (p<0.001), and diabetes (p<0.001) showed significant differences between subjects with office shift work, irregular shift work, and the control group. Conclusion. Elevated levels of IL-37 and TSH in shift workers may serve as biomarkers of the impact of shift work and the workplace on the immunological and hormonal status of employees.

Objective. Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that substantially impairs quality of life. This study aimed to assess the relationship between metabolic parameters and DPN severity in T2DM patients. Methods. A prospective observational study was conducted at PSG Institute of Medical Sciences and Research (Peelamedu, Coimbatore, India) from August 2023 to August 2024, enrolling 90 adults with T2DM on oral hypoglycemic agents after ethical approval and informed consent. Blood samples were analyzed for fasting glucose, HbA1c, lipid profile, and plasma insulin. The LDL/HDL ratio and HOMA-IR were calculated to evaluate metabolic status. DPN severity was measured using a biothesiometer. Results. The higher HbA1c levels significantly correlated with increased neuropathy severity (severe: 12.1±1.3% vs. mild: 8.4±2.0%; p=0.002). LDL/HDL ratio was elevated in patients with severe DPN (3.6±1.8) compared to mild DPN cases (2.5±1.0), but this difference was not significant (p=0.12). Severe DPN cases also showed higher HOMA-IR (10.2±2.8) suggesting a possible link to insulin resistance though not statistically significant (p=0.23). Conclusion. HbA1c strongly associates with DPN severity, while LDL/HDL ratio and HOMAIR showed no significant correlation. Further research is needed to clarify these metabolic relationships and their clinical relevance.

Objective. Cardiovascular complications are highly prevalent in type 2 diabetes mellitus (T2DM) driven by obesity, dyslipidemia, hypertension, and hypercoagulability associated with insulin resistance. The purpose of this study was to elucidate the effects of combined treatment with acetyl-L-carnitine (ALC), alpha-lipoic acid (ALA), and nicotinamide (NAm) on diabetes-induced metabolic, hemostatic, and heart abnormalities. Methods. Male non-linear Wistar rats were fed with a high-calorie diet for 2 months followed by a single low-dose streptozotocin injection to induce T2DM. Two weeks later, the diabetic rats received ALC (100 mg/kg), ALA (50 mg/kg), and NAm (100 mg/kg) for 2 weeks in separate daily injections. Fasting blood glucose, glycated hemoglobin (HbA1c), and hemostatic parameters: fibrinogen, protein C, factor X, plasminogen activator inhibitor-1 (PAI-1), were measured. The NAD+ content and NAD⁺/NADH ratio were assessed in the heart tissue. Results. After 12 weeks, blood glucose and HbA1c levels in diabetic rats were 1.8-fold and 2-fold higher, respectively. Diabetes increased fibrinogen (1.5-fold) and PAI-1 (1.7-fold) levels, caused the appearance of soluble fibrin monomers complexes, while protein C and factor X levels were decreased by 18% and 19%, respectively, indicating hypercoagulability and impaired fibrinolysis. In diabetic rats, the cardiac NAD+ level was reduced by 48%. The NAD+/NADH ratio decreased by 2-fold. Combined treatment lowered the glucose levels by 1.3-fold and HbA1c by 1.7-fold and improved the NAD+ metabolism and partially corrected the hemostatic abnormalities. Conclusion. Co-treatment with ALC, ALA, and NAm improved the glycemic control, partially restored the cardiac NAD⁺ metabolism and reduced the hemostatic abnormalities in T2DM suggesting their potential as a safe adjunct therapy for diabetes-associated cardiovascular complications.

Objective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a role in management of type 2 diabetes (T2D) and obesity by promoting glycemic control and weight reduction. Beyond these benefits, GLP-1 RAs have demonstrated positive effects on cardiovascular, renal, and neurological health, with emerging evidence supporting their therapeutic potential in conditions such as chronic kidney disease, asthma, obstructive sleep apnea, Parkinson's disease, and Alzheimer's disease. However, their widespread clinical use is often hindered by gastrointestinal side effects including nausea, anorexia, vomiting, and diarrhea that limit adherence and dose titration. Effective management of these adverse effects is essential to optimize treatment outcomes and maintain long-term therapy. Case report. A 72-year-old woman with a history of cognitive impairment, T2D, atrial fibrillation, obesity, and mood disorders presented with persistent gastrointestinal symptoms while receiving semaglutide. Dose escalation was restricted due to severe nausea, vomiting, and diarrhea, which markedly affected her quality of life. To manage these symptoms, mirtazapine was initiated. Following its introduction, the patient reported significant improvement in gastrointestinal tolerance enabling continued semaglutide therapy and successful dose advancement. Additional benefits included enhanced mood, better sleep, and overall well-being. No adverse effects related to mirtazapine were observed throughout the treatment. Conclusion. This case suggests that mirtazapine may be beneficial in mitigating GLP-1 RA-induced gastrointestinal side effects, thereby improving adherence and therapeutic efficacy. Further research is needed to evaluate the safety, mechanism, and generalizability of this approach in broader clinical practice.

Objective. The study aims to evaluate the severity of endogenous intoxication and characterize morpho-functional liver changes during experimental acute generalized peritonitis (AGP) in diabetic rats. Methods. Fifty-six adult male Wistar rats were used, including 8 controls and 48 males with experimental pathology. Diabetes mellitus was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg). On day 14, AGP was induced by i.p. injection of a 10% filtered fecal suspension. Endogenous intoxication was assessed by measuring hydrophilic and hydrophobic molecular products in the blood. Liver function was evaluated by serum aminotransferase activity, total protein, and protein fractions. Histological analysis of liver tissue was performed using standard hematoxylin-eosin staining. Results. A progressive increase in endogenous intoxication was observed peaking on day 7. This was marked by a significant elevation in middle molecular weight molecule (MMWM) concentrations at wavelengths of 254 nm and 280 nm by 103.0% (p<0.001) and 340.0% (p<0.001), respectively. The erythrocyte intoxication index (EII) increased by 148.8% (p<0.001) compared to controls. Concurrently, aminotransferase activity increased, while serum total protein and albumin levels decreased. Histologically, inflammatory infiltration and vascular congestion were evident on day 1 progressing to hepatocellular dystrophy and necrosis by day 3. By day 7, signs of hepatic failure were present including disruption of trabecular architecture, hydropic degeneration, intra-cellular cholestasis, and portal tract expansion due to vascular hyperemia. Conclusions. Experimental acute generalized peritonitis in diabetic rats resulted in a pronounced endogenous intoxication accompanied by progressive morpho-functional liver damage culminating in hepatic insufficiency by day 7.

Head and neck tumors are common in Slovakia. Although the number of tumors associated with smoking and alcohol is decreasing, the number of tumors associated with human papilloma-virus increases. Radiotherapy plays an important role in their treatment. The thyroid gland, due to its oneself location, is predisposed to the development of post-radiation dysfunction. Nowadays, there are methods able to reduce this risk and also available new options for treatment and dispensary care for these patients. The aim of this work is to analyze the incidence and pathophysiological mechanisms of post-radiation hypothyroidism in patients with head and neck tumors, to highlight the risk factors associated with radiotherapy and evaluation of prevention possibilities and treatments, and an overview of modern therapeutic approaches. Special attention is devoted to the importance of a multidisciplinary approach and the need for a long-term patient monitoring as well as the assessment of thyroid function as an integral part of a comprehensive oncological care.

Objective. Elevated prolactin levels (hyperprolactinemia) is an endocrine disorder associated with metabolic dysfunctions such as insulin resistance, obesity, dyslipidemia, and glucose intolerance on many occasions. Type 2 diabetes mellitus (T2DM) is a major risk factor for insulin resistance, which is one of the most important determinants of overweight males for hyperprolactinemia. The purpose of this study was to investigate the impact of hyperprolactinemia on insulin resistance parameters including HOMA-IR, QUICKI, TG/HDL, and TyG index values in overweight male patients. Patients and Methods. A total of 90 participants were involved in a case-control study including 45 overweight males with hyperprolactinemia and 45 age- and BMI-matched healthy controls. Blood samples were collected for measurement of fasting glucose, insulin, lipid profile, testosterone, and prolactin. HOMA-IR, QUICKI, TyG index, TG/HDL ratio were used to assess insulin resistance. Results. In hyperprolactinemic individuals, fasting insulin levels, HOMA-IR, and the TyG index were elevated, which indicates increased insulin resistance. In addition, these patients had lower QUICKI values corresponding to lower insulin sensitivity. This was also related to the fact that there was a significant elevation in triglycerides and LDL levels as well as a decrease in HDL. Testosterone was turned negatively with high prolactin level (p<0.01), followed by insulin resistance markers, which were positively correlated with increased prolactin (p<0.001). Conclusions. The results suggest that hyperprolactinemia has a strong association with insulin resistance in overweight males. The elevated prolactin levels found in testosterone deficiency also led to a dysregulated glucose metabolism and lipid abnormalities, and hormonal imbalance underlying the rationale for early screening and metabolic interventions.

Objective. Graves' disease is an autoimmune disease of the thyroid gland causing hyperthyroidism due to thyroid-stimulating hormone receptor autoantibodies. A rare, but serious complication of anti-thyroid drug therapy is agranulocytosis, a critical reduction in granulocytes leading to neutropenia and impaired infection defense. Case report. We report a case of a 32-year-old woman with Graves' disease who developed propylthiouracil-induced agranulocytosis and pancytopenia with concurrent severe infection. The patient was treated with antibiotics and granulocyte colony-stimulating factor ultimately undergoing total thyroidectomy. Conclusion. The case highlights a rare, but potentially life-threatening complication of antithyroid drug therapy. We emphasize the importance of close monitoring of patients treated with anti-thyroid drugs. Early recognition and prompt intervention are crucial as agranulocytosis is not always symptomatic. Additionally, early thyroidectomy should be considered in women of childbearing age as recurrent disease flares and therapeutic switching not only increase the risk of agranulocytosis and infection, but may also delay pregnancy.