Clinical heterogeneity of polish patients with KAT6B-related disorder.

BACKGROUND: Say-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B-related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B-related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis. METHODS: Here we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS). RESULTS: We present a detailed phenotypic analysis of six individuals with KAT6B-related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B-related disorders. CONCLUSION: While most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.

Foot drop in children with newly diagnosed type 1 diabetes: three case reports.

Summary: The etiology of foot drop is diverse from various diseases to mechanic injuries and includes neuropathy of the peroneal nerve. Peroneal neuropathy might also be one of the forms of diabetic neuropathy, very rarely reported as the first sign of diabetes. We describe three cases of children with newly diagnosed type 1 diabetes (TID) who developed unilateral peroneal nerve palsies and tibial nerve palsies, presenting clinically as a foot drop. In two of our cases, the symptoms of foot drop occurred shortly after starting treatment for severe diabetes ketoacidosis. In the third patient, food drop was a reason for the initial medical consultation, but eventually, TID was diagnosed. The presented cases highlight that neuropathy can be observed not only as a chronic complication of T1D, but it can also appear at the time of disease manifestation. The incorrect position of the lower limb during a keto coma may contribute to the development of neuropathy. Learning points: Neuropathy can be observed not only as a chronic complication of type 1 diabetes (T1D), but it can also appear at the time of disease manifestation. The incorrect position of the lower limb causing external pressure during a keto coma may contribute to the development of neuropathy. It is important to examine the glycemia in patients with acute peroneal neuropathy, as this kind of peripheral neuropathy can be associated with newly diagnosed T1D. Normalization of glycemia might lead to rapid neuronal recovery.

Weight gain in type 1 diabetes during the SARS-CoV-2 pandemic. Does lockdown affect the metabolic control of pediatric patients?

Background and aims: Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population. Methods: Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed. Results: A total of 185 patients with T1D were included in the study (96 boys), aged 2-18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m2 vs. 20.9 ± 4.1 kg/m2, p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period. Conclusions: The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.

Prevalence of haplotype DQ2/DQ8 and celiac disease in children with type 1 diabetes.

Type 1 diabetes (T1D) and celiac disease (CD) coexist very often. Identification of the human leukocyte antigen (HLA) DQ2/DQ8 can confirm the genetic predisposition to CD. Negative result of this test allows to exclude CD with a high probability. It was suggested that in individuals with higher risk of CD, including T1D patients, the implementation of genetic testing should reduce the number of patients requiring systematic immunological screening. The aim of this study was to analyze the prevalence of different haplotypes predisposing to CD in children and adolescents with previously diagnosed T1D. MATERIAL AND METHODS: A retrospective analysis was performed on 166 T1D children (91 girls) in whom HLA DQ2/DQ8 alleles were tested. In 9.6% CD was also diagnosed. RESULTS: In 12.7% both HLA DQ2/DQ8 were negative. In 87.3% patients HLA DQ2 and/or DQ8 was positive, including 27.7% patients with both haplotypes DQ2.5 and DQ8 positive. In all CD patients the disease predisposing alleles were positive, while none of the HLA DQ2/DQ8 negative children were diagnosed with CD. CONCLUSIONS: The prevalence of HLA DQ2.5 and the HLA DQ2.5 / HLA DQ8 configuration is higher in patients with T1D, and CD compared to children with T1D alone. The combination of HLA DQ2 and HLA DQ8 most significantly increases the risk of developing CD. The group of HLA DQ2/DQ8 negative patients with improbable CD diagnosis, is relatively small. Most of T1D patients HLA DQ2/DQ8 positive need further regular antibody assessment. In patients with T1D, who are at high risk of developing CD, genetic testing may be considered to select those who require further systematic serological evaluation. Due to its retrospective nature, the study was not registered in the database of clinical trials and the Clinical trial registration number is not available.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

To increase body height and muscle strength - one medicine for two diseases? Case report of a boy with Silver-Russell syndrome and Duchenne muscular dystrophy.

The coexistence of 2 genetic diseases can mutually modify their course. We describe the case of a 10-year-old boy with Sliver-Russell syndrome (SRS) and Duchenne muscular dystrophy (DMD). The patient's short stature, which is part of the clinical picture of both diseases, has been additionally aggravated by the steroid therapy, which is necessary to delay the progression of DMD. From the age of 9 years, the patient was treated with recombinant human growth hormone (rhGH) for 18 months. The following study discusses whether rhGH therapy in a child with SRS and DMD may alleviate or worsen the course of DMD, and how it affects carbohydrate metabolism disorders.

Evaluation of Vascular Endothelial Function in Children with Type 1 Diabetes Mellitus.

Diabetic kidney disease belongs to the major complications of diabetes mellitus. Here, hyperglycaemia is a key metabolic factor that causes endothelial dysfunction and vascular changes within the renal glomerulus. The aim of the present study was to assess the function of the vascular endothelium in children with type 1 diabetes mellitus (type 1 diabetes) by measuring selected endothelial lesion markers in blood serum. The selected markers of endothelial lesions (sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE) were assayed by the immunoenzymatic ELISA method. The study involved 66 patients (age: 5-18 years) with type 1 diabetes and 21 healthy controls (age: 5-16 years). In the type 1 diabetes patients, significantly higher concentrations of all of the assayed markers were observed compared to the healthy controls (p < 0.001). All of the evaluated markers positively correlated with the disease duration, the age, and BMI of the patients, while only PAI-1 and sE-SELECTIN were characteristic of linear correlations with the estimated glomerular filtration rate (eGFR). It can be concluded that endothelial inflammatory disease occurs in the early stages of type 1 diabetes mellitus in children. The correlations between PAI-1, sE-SELECTIN, and eGFR suggest an advantage of these markers over other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in children with type 1 diabetes.

Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control.

Klotho concentration may be considered as a prognostic factor in the development of chronic complications of diabetes. Moreover, decrease in sKlotho concentration may contribute to beta cell apoptosis and type 1 diabetes development. The aim of this study was to evaluate if sKlotho protein concentration in children with type 1 diabetes (T1D) and its correlation with classical risk factors of chronic complications of diabetes: dysglycemia and endothelial dysfunction. Material and methods: In a cross-section single center study the levels of soluble Klotho protein in 80 T1D (37 boys) and 34 healthy children (controls, 15 boys). Micro- and macroangiopathy were excluded and renal function was normal in all participants. Serum sKlotho, sICAM-1, sVCAM-1 and E-selectin levels were measured. Results: The concentration of sKlotho was lower in T1D than in the controls (2041.9 ± 1017.6 pg/mL vs. 2790.3 ± 1423.9 pg/mL, p=0.0113). sICAM-1, sVCAM-1 and E-selectin concentrations were comparable in patients and controls. In T1D, sKlotho was not correlated with the duration of diabetes. Klotho and E-selectin were correlated with HbA1c (r=-0.31, P=0.0066 and r=0.25, P=0.0351, respectively), but not with AVBG and blood glucose SD. Correlations of sKlotho with total cholesterol (r=0.31, P=0.0129), HDL-cholesterol (r=0.43, P=0.0011) and LDL-cholesterol (r=0.28, P=0.0412), but not with triglycerides, were found. Likewise, Klotho was not correlated with sICAM-1, sVCAM-1, and E-selectin concentrations. Conclusions: This study reports the significantly lower level of s-Klotho in children with type 1 diabetes, correlated with HbA1c and HDL cholesterol, but not with the adhesion molecules concentrations nor the duration of the disease. Negative correlation between the levels of HbA1c and soluble Klotho may suggest its possible involvement in the development of chronic diabetes complications.

Disturbances in the intraventricular conduction system in teenagers with type 1 diabetes. A pilot study.

Body Surface Potential Mapping (BSPM) is a multi-electrode synchronous method for examining electrocardiographic records on the patients' body surface that allows the assessment of changes in the heart conduction system. The aim of the study was to visualize and evaluate changes in the intraventricular system in adolescents with T1D. PATIENTS AND METHODS: Inclusion criteria: age > 12 years, T1D duration >3 years, HbA1c >8%. EXCLUSION CRITERIA: diagnosis of autonomic neuropathy, heart structural defects, heart failure. BSPM data were processed into map plotting to illustrate differences in ventricular activation time (VAT, isochron lines). RESULTS: 33 teenagers (20 boys), mean age 15.0 ± 2.1 years, T1D from 6.8 ± 4.1 years were included. Mean HbA1c was 9.6 ± 2.0%. In the standard ECG recording abnormalities were not present. The distribution of isolines on the group-mean map plotted for T1D patients only initially resembles the course of isolines on the group-map for normal subjects (N = 30), in whom the electrical impulse stimulating the heart ventricles passes through the atrio-ventricular node, then symmetrically excites the branches of His bundle and finally the Purkinje fibers. In T1D patients, after proper onset of intraventricular stimulation, the isolines reflecting the both ventricles reach higher time values, which indicates problems in the propagation of the ventricular depolarization.

Diagnosis of type 1 diabetes during the SARS-CoV-2 pandemic: Does lockdown affect the incidence and clinical status of patients?

BACKGROUND: Currently, the only effective method to control the spread of the COVID-19 pandemic is social distancing. The lockdown measures during the epidemic may have an impact on the presentation of diabetes and may disturb metabolic control. OBJECTIVES: In order to address the hypothesis that the COVID-19 lockdown affected the incidence rate (IR) of type 1 diabetes (T1D) in the pediatric population of Lower Silesia and the patients' clinical status, the incidence of T1D during the COVID-19 pandemic was analyzed. MATERIAL AND METHODS: Incidence estimates were obtained from the T1D pediatric registry for Lower Silesia which has been maintained since January 1, 2000. The observation was completed on April 30, 2020. RESULTS: A total of 1961 cases were diagnosed (1054 boys, 53.72%). An increase in the T1D IR was observed, from 10.43/100,000/year in 2000 to 22.06/100,000/year in 2019. The seasonality of T1D incidence was also observed, with the highest IR appearing in January and February. There were half as many cases of T1D in March and April 2020 as in the same months in 2019 (p > 0.05). Diabetic ketoacidosis (DKA) occurred in 31.75% of patients in years 2000-2019, comparably (p > 0.05) to 2020 (36.67% patients), including March and April (50% of patients). The duration of hyperglycemia symptoms was 20.2 ±25.4 days, which was comparable to 2020 (13.1 ±10.96 days; p = 0.1675) and March and April of 2020 (9.67 ±5.63 days; p = 0.0831). Glycated hemoglobin (HbA1c) level was 11.79 ±2.63%, which was comparable to March and April of 2020 (13.06 ±2.35%; p = 0.1171), while in all of 2020 it was 13.41 ±2.50% (p = 0.0003). CONCLUSIONS: The IR of T1D in Lower Silesian children in the months of the COVID-19 pandemic was comparable to previous years, while their clinical condition at the time of diagnosis was worse than in previous years.

Clinical evaluation of 31 children with pituitary insufficiency in the course of the pituitary stalk interruption syndrome. The unexpected growth without growth hormone in 2 children.

INTRODUCTION: The pituitary stalk interruption syndrome (PSIS) is one of the complex -forms of congenital pituitary insufficiency. Symptoms resulting from insufficiency of the pituitary gland, in spite of the inborn character of the disease, may appear at various stages of life. The aim of this paper was to present clinical presentation in 31 patients with PSIS confirmed radiologically. RESULTS: In the whole study population during first examination 25.8% children were diagnosed with combined pituitary hormone deficiency (CPHD). During the endocrinological observation (median follow-up 5.1 years, range 0.513.2) of the above-mentioned group 74.2% subjects were diagnosed with CPHD, while 25.8% patients with isolated growth hormone deficiency (GHD). Two children with initially short stature were confirmed with GHD. As a result of the parents' decision, growth hormone therapy was either not started or discontinued. During further follow-up, however, the children achieved normal height. CONCLUSIONS: Children with PSIS present a diverse clinical picture and should be observed because of the risk of further pituitary disorders. In the differential diagnosis of hypoglycemia in the neonatal period and in infancy, hypopituitarism should be considered. The phenomenon of normal growth in patients with confirmed growth hormone deficiency has been observed, although is not fully understood.

Itch in Children with Type 1 Diabetes: A Cross-Sectional Study.

INTRODUCTION: Type 1 diabetes (T1D) is reported to be one of the most common medical conditions in school-age youth and is ranked third in the prevalence of pediatric conditions. Only a few studies have investigated the occurrence of itch in diabetes mellitus, reporting conflicting data. The purpose of this study was to investigate the prevalence of itch in T1D to provide itch characteristics and to explore the potential underlying causes. METHODS: This prospective study evaluated itch among 100 children with T1D. Itch intensity was assessed with the Numerical Rating Scale (NRS) and the 4-Item Itch Questionnaire (4IIQ). The Children's Dermatology Life Quality Index (CDLQI) was implemented to assess the quality of life issues. Various clinical features and factors influencing itch were also examined. Skin dryness was evaluated clinically by non-invasive assessment of epidermis moisturizing. RESULTS: Itch occurred in 22% of children with T1D with the mean maximal intensity of 5.9 ± 3.0 points in NRS and 6.7 ± 3.5 points in 4IIQ (median, 5.5 points). In the majority of patients, the itch was limited to a few regions of the body; usually, the upper limbs (68.2%) were affected, followed by the lower limbs (50%) and the trunk (31.8%). Clinically examined skin xerosis was significantly more advanced in children with itch compared with those without itch (p < 0.01). The mean CDLQI score in the itchy group was 4.0 ± 4.7 points (median, 2.5 points), indicating a small impairment of quality of life. The intensity of itch (both NRS last 3 days and NRS last 24 h) correlated positively with life quality impairment (R = 0.7; p = 0.015 and R = 0.8, p = 0.002, respectively). CONCLUSIONS: Our study found itch as a moderately frequent symptom in children with T1D; however, itch presence and intensity may relevantly debilitate quality of life among subjects. We suggest that dryness of the skin may play a role in the pathogenesis of itch in this population.

Acute hypoxic hepatitis as a complication of diabetic ketoacidosis in a boy with newly diagnosed diabetes.

INTRODUCTION: Hypoxic hepatitis is characterised by centrilobular liver cell necrosis associated with a rapid and transient increase in serum aminotransferase levels (ALT, AST) in critically ill patients. The aim of this paper is to present a case report of a paediatric patient with severe ketoacidosis in the course of newly diagnosed diabetes types 1 complicated by hypoxic hepatitis. CASE REPORT: A boy, nearly three years old, was admitted to the hospital with ketoacidosis (pH - 7.058, BE - 28.3 mmol/l, HCO3 - 6.3 mmol/l) and glucose level of 434 mg/dl (24.1 mmol/l). After 48 hours of treatment with fluids and insulin infusion the serum glucose level and acidosis normalised. On the fourth day of hospitalisation, laboratory tests revealed a rapid increase in AST (to 12955 IU/l) and ALT (to 4328 IU/l) concentrations. Increased GGTP level (346 IU/l) and mild coagulation disorders (INR = 0.78) were also observed. In the following days a gradual decrease in transaminase and normalisation of the coagulation system were observed. CONCLUSIONS: Severe diabetic ketoacidosis with significant dehydration and hypovolaemic shock may lead to hypoxic hepatitis, also in small children.

Hyperosmolar hyperglycaemic state (HHS) as the first manifestationof type 2 diabetes in a child.

Hyperglycaemic hyperosmolar state (HHS) may occur in young patients with type 1 and type 2 diabetes and in infants with hyperglycaemia. Hyperglycaemic hyperosmolar state is characterised by extremely high glucose concentration, which, by increasing osmotic diuresis, intensifies dehydration. Hyperglycaemic hyperosmolar state criteria include the following: plasma glucose > 600 mg/dl, venous pH > 7.25, sodium bicarbonate > 15 mmol/l, slight ketonuria, plasma osmolality > 320 mOsm/kg, and impairment of consciousness (aggression, unconsciousness, convulsions). We describe the case of a 13-year-old patient with severe obesity (at presentation body mass > 120 kg, BMI > 40 kg/m2), who developed HHS (glycaemia 647 mg/dl, pH 7.18, pCO2 96.5 mmHg, BE - 5.0 mmol/l, HCO3 35.2 mmol/l; Na 167 mmol/l, plasma osmolarity 370 mOsm/kg) in the course of pneumonia and newly diagnosed type 2 diabetes (HbA1c 15.5%, C-peptide 2.63 ng/ml). In the follow-up, due to the hypoglycaemia, insulin was discontinued, metformin was administered at a dose of 2 g/day, with a further reduction to 500 mg/day, together with physical rehabilitation and a low-calorie diet. Weight reduction during 6 months of observation was approximately 37 kg. Due to breathing disorders occurring at night, the girl still needs breathing assistance (CPAP).

Comparison of the prevalence of incidental and non-incidental papillary thyroid microcarcinoma during 2008-2016: a single-center experience.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) is increasing; however, it is not clear whether this reflects an increase in the incidence of incidental or in that of non-incidentally (presurgically) discovered PTMC (IPTMC vs. NIPTMC). We assessed the incidence of IPTMC and NIPTMC over the past 9 years, to discern whether the increase in PTMC incidence is due to improved diagnostics or to a real increase in the incidence. METHODS: We performed a retrospective chart review of 4327 patients who were consecutively admitted to and surgically treated for thyroid pathology at a single institution. As a main presurgical diagnostic test, all patients underwent ultrasound-guided fine-needle aspiration biopsy (UG-FNAB). The analyzed time frame was divided into three equal periods (I: 2008-2010, II: 2011-2013, III: 2014-2016), and IPTMCs and NIPTMCs were assessed and compared in each period. RESULTS: We evaluated 393 (9.08%) patients with thyroid malignancy, of which 156 (3.60% of all thyroid tumors [TTs]; 39.69% of all thyroid cancers [TCs]) were diagnosed as PTMC. The prevalence of NIPTMC among all TCs increased from 16.66% in 2008 to 33.75% in 2016, while that of IPTMC decreased from 20.83% in 2008 to 13.75% in 2016. The incidence rates of NIPTMC and IPTMC in period III differed statistically significantly (p < 0.0001). The prevalence rate of NIPTMC in period III was higher than that in period II, yet comparable to that in period I (p = 0.0014; p = 0.2804, respectively). CONCLUSIONS: The prevalence of NIPTMC, rather than that of IPTMC, is escalating; this may be due to better presurgical diagnosis.

[Chemerin as an early marker of metabolic syndrome]. / Chemeryna (CHEM) jako wczesny marker rozwoju zaburzen zwiazanychz zespolem metabolicznym.

Chemerin (CHEM) is a protein synthesized primarily by adiposse tissue and liver. CHEM acts both paracrine and autocrine, stimulating adipocytes maturation and differentiation. In addition to its hormonal function, CHEM acts as a chemoattractant for immune cells, regulating the innate and acquired inflammatory response. Its pleiotropic properties also affect the carbohydrates and lipids metabolism. High concentrations of CHEM are observed in people with obesity, type 2 diabetes, hypertension, and hyperlipidemia - components of the metabolic syndrome. Therefore CHEM also may be considered as an early predictive marker for diagnosing metabolic syndrome, also in adolescence and childhood.

Metabolic disorders in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex disease. Depending on the used criteria the prevalence of PCOS ranges from 6 to 20%. It is necessary to exclude diseases leading to androgen excess. The participation of genetic and environmental factors is considered in the etiology of PCOS development. The highest rate of incidence of PCOS is assessed in girls who were born SGA and developed premature adrenarche later in life.The free androgen index (FAI) is concerned as the most sensitive marker of hyperandrogenaemia in PCOS although insulin resistance, anti-Müllerian hormone (AMH),and deficiency of vitamin D may intensify metabolic disturbances. The ultrasound criteria used in adolescent patients prefer the estimation of the ovarian volume or the ratio of ovarian stroma to total ovary, rather than the number of ovarian follicles. PCOS is connected with different metabolic disorders. Post-binding defect in signal transduction is responsible for insulin resistance. This defect results from an impaired activity of the kinase receptor. Moreover, the adipose tissue of PCOS women differs substantially from the tissue of the others according to morphology and function. The adipocytes produce lower amounts of adiponectin, which is an insulin-sensitizing agent. Dyspidemia with high triglycerides and low high density lipoprotein cholesterol concentrations is frequently noticed. Cardio-metabolic risk factors, insulin resistance, and endothelial dysfunction accompany PCOS from the very beginning. Oxidative stress plays a role as a link among systemic inflammation and dysfunction of endothelial cells and abnormal thecal cell action. The treatment efforts in PCOS depend on the patient's main problems. Modification of diet and lifestyle is the most important recommended advice to each woman independent of age and weight.

Should the Prevalence of Incidental Thyroid Cancer Determine the Extent of Surgery in Multinodular Goiter?

BACKGROUND: The most appropriate surgical procedure for multinodular goiter (MNG) remains under debate. Incidental thyroid carcinoma (ITC) is often identified on histopathological examination after thyroidectomy performed for presumed benign MNG. AIM OF THE STUDY: The aim of the study was to determine the value of radical surgery for MNG patients considering the prevalence of ITC diagnosed postoperatively. MATERIALS AND METHODS: We conducted retrospective analysis of the medical records of 2,306 patients surgically treated for MNG between 2008 and 2013 at one center. None of the patients presented with any suspicion of malignancy, history of familial thyroid cancer, multiple endocrine neoplasia syndrome or previous head or neck radiation exposure. RESULTS: Among the 2,306 MNG patients, ITC was detected in 49 (2.12%) (44 women and 5 men, with average ages of 52.2 (21-79) and 55.6 (52-62), respectively). Papillary thyroid carcinoma was significantly more frequently observed than other types of ITC (p<0.00001). Among the MNG patients, 866 (37.5%) underwent total/near total surgery, 464 (20.1%) received subtotal thyroidectomy, and 701 (30.3%) received the Dunhill operation. The remaining 275 (11.9%) patients underwent a less radical procedure and were classified as "others." Among the 49 (100%) patients with ITC, 28 (57.1%) underwent radical surgery. Another 21 (42.9%) patients required completion surgery due to an insufficient primary surgical procedure. A total of 21 (2.42%) patients in the total/near total surgery group were diagnosed with ITC, as well as 16 (2.48%) in the subtotal thyroidectomy group and 12 (1.71%) in the Dunhill operation group; 21 (100%), 4 (25%) and 3 (25%) of these patients, respectively, underwent radical surgery; thus, 0 (0%), 12 (75%) and 9 (75%) required completion surgery. The prevalence rates of ITC were comparable between the radical and subtotal surgery groups (2.42% and 3.44%, respectively, p = 0.4046), and the prevalence was higher in the radical surgery group than in the Dunhill operation group (2.42% and 1.71%, respectively, p = 0.0873). A significant difference was observed between the group of patients who underwent total/near total surgery, among whom all of the patients with ITC (100%) received primary radical surgery, and the groups of patients who received the subtotal and Dunhill operations, among whom only 25% of the patients with ITC in each group received primary radical surgery (p<0.0001). CONCLUSIONS: More radical procedures for MNG result in a lower risk of reoperation for ITC. The prevalence of ITC on postoperative histopathological examination should determine the extent of surgery in MNG patients. In the future, total/near total thyroidectomy should be considered for MNG patients due to the increased prevalence of ITC to avoid the necessity for reoperation.