Akromegália je raritné endokrinologické ochorenie charakterizované nadprodukciou rastového hormónu (RH), najčastej- šie na podklade adenómu hypofýzy s následnou zvýšenou produkciou inzulínu podobného rastového faktora 1 (IGF-1) v pečeni. Účinky RH a IGF-1 na metabolizmus glukózy sú antagonistické; RH vyvoláva inzulínovú rezistenciu, zatiaľ čo IGF-1 zvyšuje inzulínovú citlivosť. Avšak inzulín-antagonizujúci účinok RH prevyšuje inzulín-senzitizujúci účinok IGF-1 v cieľových tkanivách, čo vedie k vzniku diabetes mellitus (DM) pri akromegálii. Sekundárny DM je častou komplikáciou u pacientov s akromegáliou. DM môže byť prvým prejavom ochorenia, pretože hyperglykémia spôsobená inzulínovou rezistenciou býva často významná. Diagnostika a liečba DM u pacientov s akromegáliou je komplexná a vyžaduje multidisciplinárny prístup, ktorý zahŕňa endokrinológov, diabetológov a ďalších špecialistov. Účinná kontrola akromegálie prostredníctvom chirurgického zákroku, farmakoterapie alebo rádioterapie môže zlepšiť glukózovú homeostázu a znížiť riziko komplikácií spojených s DM. Uvedený prehľadový článok sa zaoberá patofyziologickými a klinickými zvláštnosťami DM u pacientov s akromegáliou, ako aj potenciálnymi účinkami špecifickej liečby akromegálie na glukózovú homeostázu.

Acromegaly is a rare endocrine disorder characterized by the overproduction of growth hormone (GH), most commonly due to a pituitary adenoma, leading to increased production of insulin-like growth factor 1 (IGF-1) in the liver. The effects of GH and IGF-1 on glucose metabolism are antagonistic; GH induces insulin resistance, while IGF-1 enhances insulin sensitivity. However, the insulin-antagonizing effect of GH outweighs the insulin-sensitizing effect of IGF-1 in target tissues, leading to the development of diabetes mellitus (DM) in acromegaly.Secondary DM is a frequent complication in patients with acromegaly. In fact, DM may be the first manifestation of the disease, because hyperglycemia caused by insulin resistance is often significant. The diagnosis and management of DM in patients with acromegaly are complex and require a multidisciplinary approach involving endocrinologists, diabetologists, and other specialists. Effective control of acromegaly through surgery, pharmacotherapy, or radiotherapy can improve glucose homeostasis and reduce the risk of complications associated with DM. This review article discusses the pathophysiological and clinical characteristics of DM in patients with acromegaly, as well as the potential effects of specific acromegaly treatments on glucose homeostasis.

• MeSH
• Acromegaly * diagnosis   etiology   drug therapy   MeSH
• Diabetes Mellitus etiology   MeSH
• Dopamine analogs & derivatives   MeSH
• Glucose metabolism   MeSH
• Insulin-Like Growth Factor I metabolism   MeSH
• Insulin Resistance MeSH
• Humans MeSH
• Growth Hormone analogs & derivatives   blood   MeSH
• Blood Glucose Self-Monitoring MeSH
• Somatostatin analogs & derivatives   MeSH
• Check Tag
• Humans MeSH

BACKGROUND: Cognitive impairment is a well-recognized symptom of multiple sclerosis (MS) that can manifest early in the disease course. Deficits in cognitive function can have a major impact on daily life. However, cognitive decline is often under-examined in clinical trials and clinical practice due to lack of adequate data. The objective of this study was to examine the longitudinal effect of ocrelizumab vs interferon beta (IFNβ)-1a on cognitive impairment in 2 phase 3 studies in relapsing MS (RMS). METHODS: The pooled population of participants with RMS (n = 1656) from the OPERA I/II clinical trials received subcutaneous IFNβ-1a (44 μg; n = 829) 3 times weekly or intravenous ocrelizumab (600 mg; n = 827) every 24 weeks. Cognition was assessed with a Symbol Digit Modalities Test (SDMT), administered in written or oral form according to each site investigator's choice, that primarily measured cognitive processing speed at baseline and every 12 weeks until the end of the double-blind treatment (96 weeks). Treatment effects were investigated based on longitudinal linear models for the change from baseline in SDMT and Cox regression for the time to 12- or 24-week confirmed decline of ≥4 points. RESULTS: Among the participants with an SDMT assessment at baseline and ≥1 postbaseline time point (IFNβ-1a, n = 749; ocrelizumab, n = 766), ocrelizumab treatment was associated with a greater mean SDMT improvement over 96 weeks than IFNβ-1a treatment (5.4 [95 % CI, 4.4-6.5] vs 4.0 [95 % CI, 3.0-5.1]; adjusted mean difference, 1.4 [95 % CI, 0.05-2.72]; P = 0.042). The risk of a clinically meaningful SDMT decline (≥4 points) was lower for those treated with ocrelizumab for both ≥12 weeks (IFNβ-1a, 18.4 %; ocrelizumab, 12.7 %; hazard ratio, 0.63 [95 % CI, 0.47-0.85]; P = 0.003) and ≥24 weeks (IFNβ-1a, 12.9 %; ocrelizumab, 7.9 %; HR, 0.57 [95 % CI, 0.39-0.82]; P = 0.003). CONCLUSION: Ocrelizumab treatment resulted in better cognitive outcomes as measured by SDMT in participants with RMS compared with IFNβ-1a treatment. However, methodological limitations need to be considered when interpreting these data. CLINICALTRIALS: gov: NCT01247324, NCT01412333.

• MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   pharmacology   adverse effects   MeSH
• Immunologic Factors * administration & dosage   adverse effects   pharmacology   MeSH
• Interferon beta-1a * administration & dosage   pharmacology   MeSH
• Cognitive Dysfunction etiology   drug therapy   chemically induced   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

BACKGROUND: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. METHODS: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions. RESULTS: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. CONCLUSIONS: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.

• MeSH
• Adult MeSH
• Hyperplasia MeSH
• Carotid Body * pathology   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Head and Neck Neoplasms * genetics   pathology   diagnostic imaging   MeSH
• Paraganglioma * genetics   diagnostic imaging   pathology   MeSH
• Tomography, X-Ray Computed MeSH
• Positron-Emission Tomography MeSH
• Basic Helix-Loop-Helix Transcription Factors * genetics   analysis   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Despite advances in neonatal care, neonatal jaundice remains a common problem in maternity wards. The present retrospective epidemiological study collected data on a sample of 710 newborns and compared the incidence of neonatal jaundice in infants born to Rh (D) negative and 0 Rh (D) positive mothers. The primary aim was to determine whether the higher incidence of maternal alloimmunisation in newborns was causally related to a potentially higher incidence of neonatal jaundice in newborns of 0 Rh (D) positive mothers. To the end, we investigated a possible association between the incidence of neonatal jaundice in 0 Rh (D) positive mothers and the neonatal blood group. The incidence of neonatal jaundice was not found to differ between maternal blood groups. We discuss new preventive measures that may reduce the incidence of neonatal jaundice and thereby reduce the length of hospital stay.

• MeSH
• Incidence MeSH
• Rh-Hr Blood-Group System MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Jaundice, Neonatal * epidemiology   etiology   MeSH
• Retrospective Studies MeSH
• Rh Isoimmunization epidemiology   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.

• MeSH
• Androgens MeSH
• Androgen Antagonists adverse effects   MeSH
• Gonadotropin-Releasing Hormone therapeutic use   MeSH
• Cardiovascular Diseases * epidemiology   MeSH
• Humans MeSH
• Metabolic Syndrome * epidemiology   MeSH
• Prostatic Neoplasms * drug therapy   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Review MeSH

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

• MeSH
• Adiponectin metabolism   blood   MeSH
• Hypoxia-Inducible Factor 1, alpha Subunit * metabolism   MeSH
• NF-E2-Related Factor 2 metabolism   MeSH
• Follicle Stimulating Hormone blood   MeSH
• gamma-Aminobutyric Acid metabolism   MeSH
• Gonadotropin-Releasing Hormone metabolism   MeSH
• Hypothalamus * metabolism   drug effects   pathology   MeSH
• Insulin Resistance MeSH
• Rats MeSH
• Leptin blood   metabolism   MeSH
• Letrozole pharmacology   MeSH
• Luteinizing Hormone blood   MeSH
• Disease Models, Animal MeSH
• Rats, Wistar * MeSH
• Pyroptosis * drug effects   MeSH
• Polycystic Ovary Syndrome * chemically induced   metabolism   drug therapy   pathology   MeSH
• Testosterone blood   MeSH
• Triglycerides blood   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

V tomto článku sa venujeme endokrinne sprostredkovanej osteoporóze spôsobenej poruchami sekrécie rastového hormónu (RH); nedostatku rastového hormónu u dospelých a akromegálii. RH a inzulínu podobný rastový faktor-1 (IGF-1) stimulujú lineárny rast kostí prostredníctvom komplexných hormonálnych interakcií a aktivujú epifýzové prechondrocyty. GH prostredníctvom receptorového aktivátora jadrového faktora-kappaB (RANK), jeho ligandu (RANK-L) a osteoprotegerínového systému stimuluje produkciu osteoprotegerínu a jeho akumuláciu v kostnej matrici. Nesprávna funkcia tohto mechanizmu môže viesť k špecifickému poškodeniu kostí. Primárnym problémom kostného postihnutia pri poruchách sekrécie rastového hormónu je riziko osteoporotických fraktúr, preto je dôležité posúdiť kvalitu kosti, ktorá lepšie odráža skutočnú predispozíciu pacienta na fraktúru. Metódou odhadu kvality kostí z DXA skenov bedrovej chrbtice je trabekulárne kostné skóre (TBS). Pri akromegálii TBS lepšie definuje riziko zlomeniny, pretože BMD je normálna alebo dokonca zvýšená. TBS pomáha sledovať efekt liečby rastovým hormónom a vitamínom D. Napriek týmto zisteniam by sa TBS nemal používať samostatne, ale je potrebné komplexné zváženie všetkých rizikových faktorov zlomenín, BMD a markerov kostného obratu.

In this article, we address endocrine-mediated osteoporosis caused by disorders of growth hormone (GH) secretion; growth hormone deficiency in adults and acromegaly. GH and insulin-like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activate epiphyseal prechondrocytes. GH stimulates the production of osteoprotegerin and its accumulation in the bone matrix through the receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L) and the osteoprotegerin system. Incorrect function of this mechanism can lead to specific bone damage. The primary problem of bone involvement in disorders of GH secretion is the risk of osteoporotic fractures, so it is important to assess the quality of the bone, which better reflects the actual predisposition of the patient to fracture. The method for estimating bone quality from DXA scans of the lumbar spine is the trabecular bone score (TBS). In acromegaly, TBS better defines fracture risk because BMD is normal or even elevated. TBS helps to monitor the effect of treatment with growth hormone and vitamin D. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and markers of bone turnover is required.

• Keywords
• trabekulární kostní skóre,
• MeSH
• Absorptiometry, Photon methods   MeSH
• Acromegaly diagnosis   complications   MeSH
• Insulin-Like Growth Factor I deficiency   MeSH
• Bone Density * drug effects   MeSH
• Humans MeSH
• Osteoporotic Fractures etiology   prevention & control   MeSH
• Osteoporosis etiology   MeSH
• Growth Hormone * deficiency   therapeutic use   MeSH
• Vitamin D therapeutic use   MeSH
• Check Tag
• Humans MeSH

PURPOSE OF THE STUDY: To investigate the effects of anatomical variations on the mechanism of scaphoid fracture by comparing the radiologic parameters of the wrist of patients with and without scaphoid fracture after a fall on an outstretched hand. MATERIAL AND METHODS: Cross-sectional comparative retrospective analysis of radiographs of patients with (Group 1, n=169) and without scaphoid fracture (Group 2, n=188). Morphometric data were measured including radial inclination (RI), radial height (RH), ulnar variance (UV), carpal height (CH) ratio, revised carpal height (RCH) ratio and palmar tilt of the distal radius (PT). Receiver operating characteristics (ROC) curve analysis was used to assess the diagnostic performance for each variable with statistically significant difference. RESULTS: The mean RI and PT degrees and RH length were statistically significantly higher, and the mean UV was lower in Group 1 compared to Group 2. No difference was determined between the groups with respect to the CH ratio and RCH ratio. With ROC curve analysis, the cut-off value with the highest odds ratio was determined as RH (Cut-off value=10.77 mm, OR=21.886). CONCLUSIONS: Although higher RI, RH, PT values and more negative ulnar variance were observed in the scaphoid fracture group compared to the non-fracture group, ROC curve analysis showed that only increased RH can be considered as a possible risk factor for scaphoid fractures after fall on an outstretched hand. KEY WORDS: radiographs, risk factor, scaphoid fracture, wrist morphology.

• MeSH
• Scaphoid Bone * injuries   diagnostic imaging   MeSH
• Adult MeSH
• Fractures, Bone * diagnostic imaging   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Wrist Injuries diagnostic imaging   etiology   MeSH
• Cross-Sectional Studies MeSH
• Radiography * methods   MeSH
• Retrospective Studies MeSH
• Accidental Falls * MeSH
• Wrist Joint diagnostic imaging   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

• MeSH
• Diabetes Mellitus, Type 2 therapy   MeSH
• Humans MeSH
• Metabolic Diseases * therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH

BACKGROUND: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. METHODS AND RESULTS: We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events. CONCLUSIONS: In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

• MeSH
• Time Factors MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Testing methods   MeSH
• Genotype * MeSH
• Cardiomyopathy, Hypertrophic * genetics   mortality   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Death, Sudden, Cardiac etiology   epidemiology   MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Risk Factors MeSH
• Aged MeSH
• Heart Failure genetics   mortality   MeSH
• Heart Transplantation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH