AIM: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. METHODS: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. RESULTS: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. CONCLUSIONS: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

• MeSH
• 17-alfa-hydroxyprogesteron * krev   MeSH
• falešně negativní reakce MeSH
• kongenitální adrenální hyperplazie * diagnóza   krev   epidemiologie   genetika   MeSH
• lidé MeSH
• novorozenec MeSH
• novorozenecký screening * MeSH
• steroid-21-hydroxylasa * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• 17-alfa-hydroxyprogesteron * MeSH
• steroid-21-hydroxylasa * MeSH

INTRODUCTION: Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate and vitamin D metabolism in the kidney, and its higher levels in plasma are associated with poorer outcomes in kidney and cardiovascular diseases. It is produced by bone cells upon enhanced oxidative stress and inhibits renal phosphate reabsorption and calcitriol (active form of vitamin D) production. Bilirubin, the final product of the heme catabolic pathway in the vascular bed, has versatile biological functions, including antioxidant and anti-inflammatory effects. This study explored whether bilirubin alters FGF23 production. METHODS: Experiments were performed using UMR106 osteoblast-like cells. Fgf23 transcript levels were determined by quantitative real-time polymerase chain reaction, C-terminal and intact FGF23 protein levels were determined by enzyme-linked immunosorbent assay, and cellular oxidative stress was assessed by CellROX assay. RESULTS: Unconjugated bilirubin down-regulated Fgf23 gene transcription and FGF23 protein abundance; these effects were paralleled by lower cellular oxidative stress levels. Also, conjugated bilirubin reduced Fgf23 mRNA abundance. CONCLUSION: Bilirubin down-regulates FGF23 production in UMR106 cells, an effect likely to be dependent on the reduction of cellular oxidative stress.

• MeSH
• bilirubin * farmakologie   MeSH
• fibroblastové růstové faktory MeSH
• fibroblastový růstový faktor 23 * MeSH
• fosfáty metabolismus   MeSH
• osteoblasty MeSH
• oxidační stres MeSH
• vitamin D MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bilirubin * MeSH
• fibroblastové růstové faktory MeSH
• fibroblastový růstový faktor 23 * MeSH
• fosfáty MeSH
• vitamin D MeSH

BACKGROUND: Surgery is, next to medical and radiation therapy, the mainstay therapy for pituitary adenomas. While scientific consensus regarding the key aspects of pituitary surgery exists among neurosurgeons, procedures are not standardized and might vary significantly between hospitals and surgeons. OBJECTIVE: To provide an overview of how neurosurgical departments in Germany manage pituitary surgery. METHODS: Responses from the European Pituitary Adenoma Surgery Survey were analyzed. The survey contained 60 questions regarding demographics, training, surgical and endocrinological aspects, and patient management. RESULTS: Sixty neurosurgical centers from Germany responded to the survey. Among the centers, 35.3% (n=18) exclusively use the microscopic and 31.1% (n=14) the endoscopic technique; all other centers (n=28) use both approaches. Of responding centers, 20% (n=12) perform less than 10 transsphenoidal pituitary surgeries per year, and 1.7% (n=1), more than 100 operations. The number of transcranial pituitary operations is significantly smaller, with 53.3% of centers performing only 0-2 per year, 35% performing 3-5, and only one center (1.7%) performing more than 15 transcranial operations per year. In 8 centers (13.3%), surgeries are always performed together with an ENT surgeon; in 29 centers (48.4%) ENT surgeons are never involved. In most centers (n=54, 90%) intraoperative MRI is not available. Image guidance (with preoperative CT and/or MRI data) is used by 91.7% of respondents (n=55). Forty-two centers (72.4%) routinely prescribe hydrocortisone after pituitary surgery, and 75% (n=45) have pituitary board meetings with endocrinologists, radiologists, and radiosurgeons. Fifty-two (86.7%) respondents perform the first follow-up scan by MRI 3-4 months after surgery. CONCLUSIONS: The data showed differences as well as similarities between centers and could help to discuss the standardization of methods and the formation of networks and certification to improve patient care.

• MeSH
• adenom * chirurgie   MeSH
• endoskopie metody   MeSH
• hypofýza chirurgie   MeSH
• lidé MeSH
• nádory hypofýzy * chirurgie   MeSH
• neurochirurgické výkony MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. METHODS: A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent's perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. RESULTS: Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p<0.001). QoL was better in patients with HNF-MODY compared with patients with T1D (p=0.006), and they did not differ in terms of treatment satisfaction. CONCLUSIONS: QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.

• MeSH
• diabetes mellitus 1. typu psychologie   terapie   MeSH
• diabetes mellitus 2. typu psychologie   terapie   MeSH
• dítě MeSH
• dospělí MeSH
• kvalita života * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• spokojenost pacientů * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVES: Impaired glucose metabolism represents one the most important cardiovascular risk factors, with steeply raising prevalence in overall population. We aimed to compare mortality risk of impaired fasting glycaemia (IFG) and overt diabetes mellitus (DM) in patients with coronary heart disease (CHD). STUDY DESIGN: prospective cohort study METHODS: A total of 1685 patients, 6-24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. Overt DM was defined as fasting glucose ≥ 7 mmol/L and/or use of antidiabetic treatment, while IFG as fasting glucose 5.6-6.99 mmol/L, but no antidiabetic medication. The main outcomes were total and cardiovascular mortality during 5 years of follow-up. RESULTS: During follow-up of 1826 days, 172 patients (10.2%) deceased, and of them 122 (7.2%) from a cardiovascular cause. Both exposures, overt DM (n=623, 37.0% of the whole sample) and IFG (n=436, 25.9%) were associated with an independent increase of 5-year total mortality, compared to normoglycemic subjects [fully adjusted hazard risk ratio (HRR) 1.63 (95%CI: 1.01-2.61)]; p=0.043 and 2.25 (95%CI: 1.45-3.50); p<0.0001, respectively]. In contrast, comparing both glucose disorders one with each other, no significant differences were found for total mortality [HRR 0.82 (0.53-1.28); p=0.33]. Taking 5-years cardiovascular mortality as outcome, similar pattern was observed [HRR 1.96 (95%CI: 1.06-3.63) and 3.84 (95%CI: 2.19-6.73) for overt DM and IFG, respectively, with HRR 0.63 (95%CI: 0.37-1.07) for comparison of both disorders]. CONCLUSIONS: Impaired fasting glycaemia adversely increases mortality of CHD patients in the same extent as overt DM.

• MeSH
• diabetes mellitus krev   diagnóza   farmakoterapie   mortalita   MeSH
• komorbidita MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• nemoci koronárních tepen krev   mortalita   MeSH
• omezení příjmu potravy krev   MeSH
• prediabetes krev   mortalita   MeSH
• prognóza MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• krevní glukóza MeSH

INTRODUCTION: Abdominal obesity is a strong cardiometabolic risk factor that often occurs as early as in childhood. The negative effect of abdominal obesity on the metabolism is partially mediated by changes to the production of the major adipocyte hormones leptin and adiponectin. Leptin/adiponectin imbalance is associated with increased risk of developing obesity and type 2 diabetes mellitus. AIM: To determine whether leptin, adiponectin and the leptin/adiponectin ratio are significant predictors of body weight loss in intensively treated children/adolescents. METHODS: 183 paediatric overweight or obese patients (71 boys and 112 girls), aged 7-16 years, were enrolled in a one-month intensive lifestyle intervention programme. Participants reduced their energy intake and engaged in a supervised exercise programme consisting of 5 physical activity units per day. The subjects were examined both before and after the intervention. RESULTS: The mean BMI decrease achieved was-2.38±0.07 kg/m² (P<0.01). The decrease in plasma leptin concentration was-16.59±0.84 ng/mL (P<0.001) and CRP-0.38±0.04 mg/L (P<0.001). Changes in adiponectin concentrations were not statistically significant. The baseline leptin/adiponectin ratio was a significant predictor of decreases in body weight (P<0.005), BMI (P<0.0001) and waist circumference (P<0.05). CONCLUSION: The leptin/adiponectin ratio at baseline may be a useful predictor of results from interventions focused on decreasing BMIs in children/adolescents.

• MeSH
• abdominální obezita * krev   patologie   terapie   MeSH
• adiponektin krev   MeSH
• behaviorální terapie * MeSH
• cvičení * MeSH
• dítě MeSH
• index tělesné hmotnosti * MeSH
• leptin krev   MeSH
• lidé MeSH
• mladiství MeSH
• obezita dětí a dospívajících * krev   patologie   terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• LEP protein, human MeSH Prohlížeč
• leptin MeSH

AIM: Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially 'protective' mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). METHODS: Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). RESULTS: Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P<0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P<0.05). CONCLUSION: Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury.

• MeSH
• biologický transport MeSH
• chronická renální insuficience metabolismus   MeSH
• diabetes mellitus 2. typu metabolismus   MeSH
• diabetické nefropatie metabolismus   MeSH
• dospělí MeSH
• erytrocyty metabolismus   MeSH
• hyperglykemie metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• thiamin metabolismus   MeSH
• transketolasa metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• thiamin MeSH
• transketolasa MeSH

Measurement of thyroid nodule stiffness by strain elastography already showed promising results. The aim of our study was to evaluate the diagnostic performance of elastography in predicting thyroid cancer by determination of strain ratio comparing nodule stiffness with thyroid tissue and surrounding neck tissues as well (carotid artery, neck muscles). Totally, 310 thyroid nodules in 275 patients were examined by conventional ultrasound and elastography prior to aspiration biopsy. 22(7.1%) thyroid carcinomas were histologically confirmed and included in the study. 39 benign nodules (27 confirmed by histology and 12 with benign cytology and at least 2 years stable ultrasound finding) formed control group. Elastography was evaluated qualitatively using 6-grade score and strain ratio to surrounding thyroid tissue, carotid artery and neck muscles was determined. High-risk elastographic score (4,5) was more frequent in carcinomas (67%) compared with benign nodules (11%, p<0.001). Significant differences in distribution of strain were found in all studied parameters except comparison with thyroid tissue in transversal dimension. Strain ratio comparing the stiffness with neck muscles had a higher negative predictive value than elastographic score and conventional ultrasound (92 vs. 83 and 82% respectively). Moreover, the combination of ultrasound and strain ratio to neck muscles increased sensitivity and negative predictive value to 100%. Our results suggest, that strain ratio to neck muscles in combination with ultrasound seems to have good sensitivity and negative predictive value for predicting thyroid cancer and may be beneficial in cases when comparison to surrounding thyroid tissue is problematic (Hashimoto thyroiditis, multinodular goiter, large nodule).

• MeSH
• arteriae carotides * diagnostické zobrazování   patofyziologie   MeSH
• dospělí MeSH
• elastografie * MeSH
• krční svaly * diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• štítná žláza * diagnostické zobrazování   patofyziologie   MeSH
• uzly štítné žlázy * diagnostické zobrazování   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumour. A common mutation of papillary thyroid carcinoma (PTC) is the somatic mutation of the BRAF (V600E) gene. AIM: The aim was to 1) determine the association of lymph node metastases of PTC with the BRAF gene mutation of primary tumour; 2) evaluate association of the BRAF mutation in the -primary tumour with clinicopathological para-meters; 3) examine the extent of genetic heterogeneity by monitoring the BRAF mutation in multicentric tumours. SUBJECTS AND METHODS: Retrospective analysis of the BRAF (V600E) mutation in PTC and PTC neck lymph node metastases in 156 patients operated from 2003 to 2012 in Prague and Zlín, the Czech Republic, using a qPCR assay. The results were correlated with clinicopathological factors. RESULTS: DNA was successfully extracted from 137 samples. The BRAF (V600E) mutation was detected in 78 cases (56.9%). The patients with BRAF p.Val600Glu mutation of primary tumour had only non-significantly higher risk of cervical lymph node metastases [OR=2.39 (95%) CI 1.00-5.75, p=0.052]. In the classic papillary variant, the BRAF (V600E) mutation was found significantly more often than in other PTC subtypes (p=0.022). We did not confirm any significant association between the BRAF (V600E) mutation and other clinicopathological findings. CONCLUSION: Except for the higher prevalence in papillary variant of PTC, BRAF p.Val600Glu mutation was not associated with other prognostic clinicopathological factors of PTC. BRAF mutation cannot be regarded as a reliable marker of node metastases in patients with PTC.

• MeSH
• dospělí MeSH
• karcinom diagnóza   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• missense mutace * MeSH
• nádory štítné žlázy diagnóza   genetika   patologie   MeSH
• následné studie MeSH
• papilární karcinom štítné žlázy MeSH
• papilární karcinom MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• retrospektivní studie MeSH
• substituce aminokyselin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH

UNLABELLED: The short stature homeobox-containing gene (SHOX) plays an important role in bone development and growth. We aimed to assess bone geometry and volumetric bone mineral density at the radius in patients with isolated SHOX deficiency and to relate these bone parameters to the severity of disproportion between the upper and the lower body segment. 17 patients with isolated SHOX deficiency (median age 12.3 yrs, range 6.7-37.2, 12 children and 5 adults) were examined by peripheral quantitative CT (pQCT) at the non-dominant forearm. Results were expressed as Z-scores using published reference data. Linear regression analyses were performed to describe associations between pQCT parameters and the severity of disproportion expressed as sitting height to standing subischial leg height ratio. Trabecular volumetric bone mineral density (vBMD) at the distal radius was normal, whereas cortical vBMD was decreased (mean Z-scores 0.34±1.5, n.s., and -2.2±2.2, p<0.001, respectively). Total bone cross-sectional area was enlarged at the diaphysis (2.1±1.2, p<0.001), while cortical bone cross-sectional area was normal (-0.51±1.4, n.s.). Consequently, cortical thickness was decreased (-1.2±1.3, p<0.01). The polar strength-strain index as a surrogate of long bone strength was normal (0.40±1.4, n.s.). We found no associations between pQCT parameters and the severity of disproportion. CONCLUSIONS: Patients with isolated SHOX deficiency are characterized by decreased cortical vBMD and cortical thickness and enlarged diaphysis. As similar changes have been described in girls with Turner syndrome, these findings suggest that haploinsufficiency of SHOX could cause characteristic skeletal anomalies at the radius.

• MeSH
• algoritmy MeSH
• diafýzy diagnostické zobrazování   MeSH
• dítě MeSH
• dospělí MeSH
• haploinsuficience * MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• kostní denzita MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová rentgenová tomografie MeSH
• poruchy růstu diagnostické zobrazování   genetika   metabolismus   patofyziologie   MeSH
• protein SHOX MeSH
• radius diagnostické zobrazování   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• velikost těla MeSH
• vývoj dítěte * MeSH
• vývoj kostí * MeSH
• vývoj mladistvých * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• homeodoménové proteiny MeSH
• protein SHOX MeSH
• SHOX protein, human MeSH Prohlížeč