Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field.

Dyslipidemia is one of the most common disorders worldwide, which, if left untreated, results in a multitude of complications. Thus proper diagnostics, which includes identifying of secondary causes of dyslipidemia is crucial. Endocrine disorders are an important cause of secondary dyslipidemia. This paper aims to review the publications on lipoprotein alterations in endocrine disorders from the past two years and provide an overview of the recent discoveries in this dynamically developing and large field. Significant changes in lipoprotein serum concentrations are present in most endocrinological diseases and can be modified with proper treatment. Some lipoproteins have also been proposed as markers in some endocrine diseases, e.g., thyroid carcinoma. From the scope of endocrine disorders, the largest number of studies explored the lipoprotein changes in polycystic ovary syndrome and in women during the menopausal and peri-menopausal period. Even though the association of thyroid disorders with dyslipidemia is already well studied, new research has delivered some exciting findings about lipoprotein alterations in euthyroid patients with either positive antithyroid peroxidase antibodies or reduced sensitivity to thyroid hormones. The problem of the adverse metabolic profile, including dyslipidemia in hypoprolactinemia has been recognized. Moreover, this review describes other significant discoveries encompassing lipoprotein alterations in disorders of the adrenals, thyroid, parathyroid glands, pituitary, and gonads. The up-to-date knowledge of the influence of endocrine disorders and hormonal changes on serum lipoproteins is prudent as it can significantly impact therapeutic decisions.

Standard therapy or additionally radioactive iodine (131I) therapy; which will stop the recurrence of glioblastoma multiforme (GBM)?

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Authors of the article pose a direct question: Is it possible to treat GBM solely with radioactive iodine (¹³¹I) therapy without employing the sodium iodide symporter (NIS) gene? After all, NIS has been detected not only in the thyroid but also in various tumours. The main author of this article (A.C.), with the assistance of her colleagues (physicians and pharmacologists), underwent ¹³¹I therapy after prior iodine inhibition, resulting in approximately 30% reduction in tumour size as revealed by magnetic resonance imaging (MRI). Classical therapy for GBM encompasses neurosurgery, conventional radiotherapy, and chemotherapy (e.g. temozolomide). Currently, tyrosine kinase inhibitors (imatinib, sunitinib, and sorafenib) are being used. Additionally, novel drugs such as crizotinib, entrectinib, or larotrectinib are being applied. Recently, personalised multimodal immunotherapy (IMI) based on anti-tumour vaccines derived from oncolytic viruses has been developed, concomitant with the advancement of cellular and molecular immunology. Thus, ¹³¹I therapy has been successfully employed for the first time in the case of GBM recurrence.

Tumour-Induced Osteomalacia-A Long Way to the Diagnosis Facilitated by [68Ga]Ga-DOTATATE PET/CT.

Background: Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. Detecting the primary tumour in TIO is challenging using conventional imaging methods. This study assesses the efficacy of [68Ga]Ga-DOTATATE PET/CT in identifying the primary tumour. Methods: Six patients with suspected TIO underwent [68Ga]Ga-DOTATATE PET/CT. The patients' clinical history and biochemical parameters were analysed. Results: [68Ga]Ga-DOTATATE PET/CT successfully identified primary tumours in four patients (femoral bones for two, iliac bone for one, subcutaneous tissue of pubic region for one). Tumour removal led to clinical and laboratory improvement. In one patient, PET/CT showed rib uptake, but the biopsy was negative. One patient showed no tumour lesions on PET/CT despite clinical evidence. Two patients had focal recurrence at the primary tumour site, detected by follow-up PET/CT. Conclusions: [68Ga]Ga-DOTATATE PET/CT is a valuable tool for detecting primary tumours in TIO, aiding in accurate diagnosis and guiding surgery, leading to improved outcomes. Further research is needed to validate these findings and explore [68Ga]Ga-DOTATATE PET/CT in other paraneoplastic syndromes.

Predictors of bone mineral density in patients receiving glucocorticoid replacement for Addison's disease.

PURPOSE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison's disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement. METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN). RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient's age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD. CONCLUSION: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.

IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations.

Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Head-to-Head Comparison of [18F]PSMA-1007 and [18F]FDG PET/CT in Patients with Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. METHODS: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. RESULTS: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. CONCLUSIONS: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype.

Genetic predisposition to differentiated thyroid cancer in the Polish population.

INTRODUCTION: Genome sequencing technologies reveal molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. OBJECTIVES: The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing data. PATIENTS AND METHODS: We analyzed sequencing data from 1076 unrelated individuals totaling over 1018 billion read pairs and yielding an average 35.26 × read depth per genome, released openly for academic and clinical research as the Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. RESULTS: The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort was compared with the frequency estimated for the non­Finnish European population obtained from the gnomAD database (gnomad.broadinstitute.org). Significant differences in variant frequency were found for the APC, ARSB, ATM, BRCA1, CHEK2, DICER1, GPD1L, INSR, KCNJ10, MYH9, PALB2, PLCB1, PLEKHG5, PTEN, RET, SEC23B, SERPINA1, SLC26A4, SMAD3, STK11, TERT, TOE1, and WRN genes. CONCLUSIONS: Even though the Polish population is genetically similar to the other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as those in the RET, CHEK2, BRCA1, SLC26A4, or TERT genes. Further studies are needed to identify genomic variants associated directly with DTC.

Impaired Expression of Humanin during Adrenocortical Carcinoma.

The discovery of mitochondria-derived peptides (MDPs) has provided a new perspective on mitochondrial function. MDPs encoded by mitochondrial DNA (mtDNA) can act as hormone-like peptides, influencing cell survival and proliferation. Among these peptides, humanin has been identified as a crucial factor for maintaining cell survival and preventing cell death under various conditions. Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy that results from adrenal hormone dysfunction. This study aimed to investigate humanin expression in the adrenal tissue and serum of patients with ACC. For the first time, our study revealed significant reduction in the mRNA expression of humanin in patients with ACC compared to healthy controls. However, no significant changes were observed in the serum humanin levels. Interestingly, we identified a positive correlation between patient age and serum humanin levels and a negative correlation between tumor size and LDL levels. While the impaired expression of humanin in patients with ACC may be attributed to mitochondrial dysfunction, an alternative explanation could be related to diminished mitochondrial copy number. Further investigations are warranted to elucidate the intricate relationship among humanin, mitochondrial function, and ACC pathology.

Expression of semaphorin 3A (SEMA3A) in breast cancer subtypes.

Breast cancer is a major health concern, and its accurate diagnosis and management depend on identifying its histological type and biological subtype. Semaphorin-3A (SEMA3A) is a membrane protein with diverse roles in cellular processes, including cancer progression and angiogenesis regulation. However, its role in breast cancer remains poorly understood. This study aimed to evaluate SEMA3A expression in breast cancer and investigate its distribution across breast cancer subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Immunohistochemical evaluation was performed on 98 breast cancer patients' tumor specimens, and SEMA3A expression was assessed in tumor cells and vessels. The study included the analysis of the Ki67 proliferation index, estrogen receptor (ER) expression, progesterone receptor (PR) expression, and HER2 status in conjunction with SEMA3A expression. Analysis indicated positive expression of SEMA3A in breast cancer cells in 60 out of 98 cases. SEMA3A expression correlated positively with Ki67 levels in tumor cells (p = 0.0005, R Spearman 0.338). Notably, a negative correlation was found between SEMA3A expression and ER and PR levels in tumor cells (p = 0.04, Spearman's R = - 0.21 and p = 0.016, Spearman's R = - 0.25 respectively). HER2 status did not significantly influence SEMA3A expression. The study demonstrated positive SEMA3A expression in tumor vessels across all subtypes in 91 out of 98 cases, suggesting its involvement in endothelial cell function. However, no significant differences in SEMA3A expression were observed between breast cancer subtypes either in vessels or tumor cells. These findings suggest that elevated SEMA3A expression may be associated with worse prognosis in breast cancer, especially in ER- and PR-negative tumors. Further investigations are warranted to fully comprehend the role of SEMA3A in breast cancer biology, which may lead to the identification of novel therapeutic targets and personalized treatment strategies for breast cancer patients.

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.

Serum Phosphorus and Calcium as Biomarkers of Disease Status in Acromegaly.

Acromegaly is a chronic disease caused by the hypersecretion of growth hormone (GH), leading to changes in the growth of visceral tissues and glucose impairment. Serum biomarkers that correlate with disease status are still unclear. This study aims to assess the potential of phosphorus and calcium as biomarkers in the clinical evaluation of patients with acromegaly and clarify their relationship with SAGIT and other common biomarkers. We retrospectively analyzed data from 306 medical records of patients with acromegaly hospitalized between 2015 and 2020. Factors such as patient biometrics, duration of disease, SAGIT score, tumor size, GH, insulin-like growth factor 1 (IGF-1), calcium, phosphorus, parathormone, and vitamin D were analyzed concerning current disease status (naïve, non-remission, remission). The results showed that serum phosphorus significantly correlated with IGF-1 and SAGIT scores for patients with active acromegaly. Specifically, the best predictor for the remission of acromegaly was a phosphorus level < 3.98 mg/dL and serum calcium levels < 9.88 mg/dL. Based on logistic regression, the higher the serum phosphorus level, the lower the odds of achieving remission (an increase in one unit leads to a decrease in the chance of about 80%). In conclusion, phosphorus and calcium can be effective biochemical markers for predicting disease status in acromegaly.

A new antiviral hypothesis and radioactive iodine therapy to other cancers, such as breast cancer, lung cancer, and glioblastoma multiforme (GBM)?

Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²4I]sodium iodide ([¹²4I]NaI) or [18F] tetrafluoroborate ([¹8F]TFB). Based on published positron emission tomography (PET) results, [¹²4I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹8F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?

MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake-A Preliminary Study.

The mitochondrial open reading frame of 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that regulates the nuclear genome during stressful conditions such as hypoxia, which is typical of exercise and training. We aim to mainly investigate the relationship between serum MOTS-c concentration and muscle strength parameters measured during the countermovement jump test with oxygen consumption (VO2) measured during the cardiopulmonary exercise test to exhaustion. Physically active healthy volunteers (17 male, three female, median age 30 years), not involved in any regular exercise program or participating in any sports competitions, performed five consecutive countermovement jump tests and cardiopulmonary exercise tests until maximal exhaustion and underwent a body composition assessment by means of bioelectrical impedance analysis, and had serum MOTS-c concentration measured at rest. Serum MOTS-c concentration was positively correlated with the average power and average and maximal force of the jumps, both overall muscle mass and leg muscle mass, but not with body fat percentage. There was no correlation with peak VO2. A higher serum MOTS-c concentration is associated with greater muscle mass, force, and power generated during jumping in healthy individuals but not exercise capacity reflected by peak VO2. More studies are needed to better understand the physiological and clinical values of these findings and why MOTS-c is better associated with measures of muscle strength and not endurance in physically active people.

Performance of a deep learning enhancement method applied to PET images acquired with a reduced acquisition time.

BACKGROUND: This study aims to evaluate the performance of a deep learning enhancement method in PET images reconstructed with a shorter acquisition time, and different reconstruction algorithms. The impact of the enhancement on clinical decisions was also assessed. MATERIAL AND METHODS: Thirty-seven subjects underwent clinical whole-body [18F]FDG PET/CT exams with an acquisition time of 1.5 min per bed position. PET images were reconstructed with the OSEM algorithm using 66% counts (imitating 1 min/bed acquisition time) and 100% counts (1.5 min/bed). Images reconstructed from 66% counts were subsequently enhanced using the SubtlePET™ (SP) deep-learning-based software, (Subtle Medical, USA) - with two different software versions (SP1 and SP2). Additionally, images obtained with 66% counts were reconstructed with QClear™ (GE, USA) algorithm and enhanced with SP2. Volumes of interest (VOI) of the lesions and reference VOIs in the liver, brain, bladder, and mediastinum were drawn on OSEM images and copied on SP images. Quantitative SUVmax values per VOI of OSEM or QClear™ and AI-enhanced 'shortened' acquisitions were compared. RESULTS: Two hundred and fifty-two VOIs were identified (37 for each reference region, and 104 for the lesions) for OSEM, SP1, SP2, and QClear™ images AI-enhanced with SP2. SUVmax values on SP1 images were lower than standard OSEM, but on SP2 differences were smaller (average difference for SP1 11.6%, for SP2 -4.5%). For images reconstructed with QClear™, SUVmax values were higher (average +8.9%, median 6.1%, SD 18.9%). For small lesions with SUVmax values range 2.0 to 4.0 decrease of measured SUVmax was much less significant with SP2 (for liver average -6.5%, median -5.6% for lesions average -5.6%, median - 6.0, SD 5.2%) and showed the best correlation with original OSEM. While no artifacts and good general diagnostic confidence were found in AI-enhanced images, SP1, the images were not equal to the original OSEM - some lesions were hard to spot. SP2 produced images with almost the same quality as the original 1.5 min/bed OSEM reconstruction. CONCLUSIONS: The studied deep learning enhancement method can be used to accelerate PET acquisitions without compromising quantitative SUVmax values. AI-based algorithms can enhance the image quality of accelerated PET acquisitions, enabling the dose reduction to the patients and improving the cost-effectiveness of PET/CT imaging.

Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology.

Over the past few years, there have been significant advances in our understanding of hypoparathyroidism (HypoPT) in terms of its epidemiology, clinical presentation, etiology, and skeletal and renal complications. Moreover, the available treatment options for HypoPT have changed. This position statement of the Expert Group of the Polish Society of Endocrinology summarizes the current state of knowledge and provides recommendations for optimal management to assist clinicians in the diagnosis, treatment, and monitoring of HypoPT in Poland. The specific aspects of HypoPT management in children, pregnant and lactating women, and patients with chronic kidney disease are also discussed. HypoPT is a rare disorder characterized by hypocalcemia and the lack or deficiency of parathyroid hormone (PTH). Hypoparathyroidism can be associated with complications, including nephrocalcinosis, nephrolithiasis, renal insufficiency, cataract, seizures, cardiac arrhythmia, depression, and an increased risk of infection. Minimizing complications of HypoPT requires careful evaluation and close monitoring of laboratory parameters. Conventional management of HypoPT has focused on maintaining serum calcium levels using oral calcium and active vitamin D. However, this approach is limited because it does not restore normal PTH function, is often associated with inadequate biochemical control, and raises concerns as to long-term side effects. HypoPT is the only classic endocrine insufficiency that is not commonly treated with the substitution of the missing hormone. Recently, recombinant human PTH(1-84) has become available, offering hope that the use of the missing hormone in the treatment of HypoPT will help achieve better control and reduce the risk of complications. However, this treatment is currently unavailable in Poland.

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 1: INTRODUCTION.

Modern treatment of glioblastoma multiforme (GBM) is based on neurosurgical methods combined with radiotherapy and chemotherapy. The prognosis for patients with GBM is extremely poor. Often, complete removal of the tumor is impossible and it often recurs. Therefore, in addition to standard regimens, modern methods such as modulated electrohyperthermia, monoclonal antibodies and individualised multimodal immunotherapy (IMI) based on vaccines and oncolytic viruses are also used in the treatment of GBM. Radioiodine therapy (RIT) also holds out hope for an effective treatment of this extremely aggressive brain tumor. The expression of the sodium iodide symporter (NIS) gene has been proven to have a positive effect on the treatment of selected cancers. Research confirm the presence of expression of this gene in GBM cells, although only in animal studies. Is it possible and therapeutically effective to treat GBM with RIT without the use of an exogenous NIS gene? The safety of therapy is relevant, as the only more serious adverse effect may be hypothyroidism. The use of RIT requires further clinical studies in patients. Perhaps it is worth revolutionizing GBM therapy to give sufferers a "new life".

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 2: IS THERE AN ALTERNATIVE THERAPY OPTION IN RECURRENT GM WHEN ALL STANDARD TREATMENTS HAVE BEEN EXHAUSTED?

Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Besides the routinely applied treatments such as neurosurgery, radiotherapy, and chemotherapy, progress is being made in the field of oncology, offering hope for improved treatment outcomes. New treatment methods include individualized multimodal immunotherapy (IMI) and modulated electro-hyperthermia. The coauthor of the above series of articles (parts 1 and 2) - A.Cz. presents the concept of a new, potentially breakthrough treatment option for recurrent GBM. A.Cz. was diagnosed with GBM in August 2021. Exhaustion of standard treatment methods, as well as immunotherapy and virotherapy, only provided temporary relief. Unfortunately, after a few months, the disease recurred. Having little to lose, A.Cz. accepted an ablative dose of 2960 MBq (80 mCi) of I131, based on available literature data. Three days before the administration of radioiodine therapy (RIT), A.Cz. prophylactically blocked the thyroid's ability to absorb the radioisotope. In June 2023, approximately 7 weeks after receiving single I131 dose, the MRI examination confirmed a 30% reduction in the tumor's size. Based on this, one can speculate that Iodine-131 therapy may be an alternative treatment option for GBM patients in the future. However, this hypothesis requires confirmation in further clinical studies.

The influence of various endocrine disruptors on the reproductive system.

Various stimulants (VS) are chemicals that disrupt the endocrine system - endocrine homeostasis of the reproductive system - which also known as endocrine-disrupting chemicals (EDCs). These substances are found in the human body, in both the blood and urine, amniotic fluid, or, among others, the adipose tissue. This article presents the current state of knowledge of the effect of EDCs and additional factors such as smoking, alcohol consumption, and cannabis on the gonads. The article is an overview of the impact of EDCs and their mechanism of action, with particular emphasis on gonads, based on databases such as PubMed, EMBASE and Google Scholar, and Web of Science available until May 2022. The impact of human exposure to bisphenol A (BPA) is not fully understood, but it has been shown that phthalates show a negative correlation in anti-androgenic activity in the case of men and women for the anti-Müllerian hormone (AMH). Smoking cigarettes and passive exposure to tobacco have a huge impact on the effects of endocrine disorders in both women and men, especially during the reproductive time. Also, the use of large amounts of cannabinoids during the reproductive years can lead to similar disorders. It has been documented that excessive alcohol consumption leads to disturbed function of the hypothalamus-pituitary-gonadal axis (HPG). Excess caffeine consumption may adversely affect male reproductive function, although this is not fully proven. Therefore, the following publication presents various stimulants (BPA, phthalates, nicotine, alcohol, cannabis) that disrupt the function of the endocrine system and, in particular, affect the function of the gonads.