The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood.

Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood. Material and Methods: The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria. Results: The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03). Conclusions: GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.

Are menstrual disorders in adolescent girls related to metabolic disorders?

INTRODUCTION: Menstrual disorders in adolescent girls are a common clinical problem. They are often accompanied by lipid and glucose metabolism disturbances. The aim of the study was to investigate to what extent the metabolic profile of adolescent girls relates to the severity of their menstrual disorders. MATERIAL AND METHODS: The study included 165 girls with menstrual disturbances and 49 regularly menstruating girls (REG) without clinical hyperandrogenism, matched for age and BMI. The subjects from the study group were divided into 2 subgroups: OLIGO - 111 girls with oligomenorrhea and SA - 54 girls with secondary amenorrhoea. In all girls, hormonal, lipid, and carbohydrate metabolism profiles were assessed. RESULTS: In the SA subgroup concentrations of total cholesterol (TC) and LDL were significantly higher than in the REG and OLIGO groups. Triglyceride (TG) concentration was also the highest in the SA group and significantly higher than in the REG group. The prevalence of lipid metabolism disorders was higher in the SA group (65%) vs. the REG (40%) and OLIGO (51%) groups. The subgroups did not differ significantly in terms of fasting and OGTT glucose and insulin as well as HOMA-IR. TyG index was significantly higher in the OLIGO and SA groups than in the REG group. BMI z-score correlated with TG, LDL, fasting and 120' OGTT glucose and insulin, HOMA-IR, and TyG and negatively with HDL. No relationship between hormonal concentration and metabolic disturbances was found. CONCLUSIONS: Adolescent girls with menstrual disorders are insulin resistant, regardless of PCOS diagnosis. The severity of menstrual disorders may be related to the incidence of lipid disorders in adolescent girls.

Subclinical hypothyroidism in children and adolescents as mild dysfunction of the thyroid gland: a single-center study.

INTRODUCTION: Subclinical hypothyroidism (SH) is a biochemical diagnosis made when a serum thyroid-stimulating hormone (TSH) is ele-vated with circulating thyroid hormone levels within their reference ranges. AIM OF THE STUDY: Aim of our prospective non-randomized study was to evaluate the course of SH. MATERIAL AND METHODS: All patients with suspicion of SH referred to the Endocrinology Outpatient Clinic between 2014 and 2018 were recruited to prospective study. RESULTS: A total of 130 patients with SH were recruited for this study. Thirty-five (26.9%) patients were followed up without levothy-roxine (L-T4) (SH-T0 group) and therapy with L-T4 was randomly introduced in 95/130 (73.1%) SH children (SH-T1 group). We did not find statistical differences in hSDS and BMI Z-score between the SH-T0 and SH-T1 groups (p = 0.761 and p = 0.843, respectively). Introducing L-T4 in patients with short stature did not affect the linear growth at the end of FU ex-pressed as hSDS. OH developed in six children (6.3%) in the SH-T1 group. After conducting a multivariate logistic regres-sion, we found that the baseline TSH concentration and BMI Z-score are possible predictors of OH. CONSLUSIONS: Our study confirmed a low risk of progression of SH to overt hypothyroidism. The majority of patients remains SH or resolved for nor-mal thyroid function. The L-T4 therapy did not effect on linear growth and body weight. The main predictor of worsening to hypothyroidism were a higher TSH level and Z-score BMI.

Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved.

Introduction: Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients. Methods: In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations). Results: We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039. Conclusion: Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care.

Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland.

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.

Components of the metabolic syndrome in girls with Turner syndrome treated with growth hormone in a long term prospective study.

Background: Components of the metabolic syndrome are more common in patients with Turner syndrome (TS) than in the general population. Long-term growth hormone (GH) treatment also affects the parameters of carbohydrate metabolism. Therefore, all these factors should be monitored in girls with TS. Objective: To assess the occurrence of metabolic syndrome components in TS girls before GH treatment and to monitor changes in metabolic parameters throughout GH therapy. Patients and method: 89 TS patients were enrolled in the study. Clinical and laboratory data after the 1st (V1), 3rd (V3), 5th (V5) and 10th (V10) year of GH therapy was available respectively in 60, 76, 50 and 22 patients. The patients' biochemical phenotypes were determined by glucose 0', 120', insulin 0', 120', HOMA-IR, Ins/Glu ratio, HDL-cholesterol and triglycerides (TG) concentration. Results: Obesity was found during V0 in 7.9% of patients,V1 - 5%, V3 - 3.9%, V5 - 2%, V10 - 0%. No patient met diagnostic criteria for diabetes. A significant increase in the basal plasma glucose 0' was found in the first five years of therapy (pV0-V1 < 0.001; pV0-V3 = 0.006; pV0-V5 < 0.001). V10 glucose 120' values were significantly lower than at the onset of GH treatment (pV0-V10 = 0.046). The serum insulin 0' and 120' concentrations as well as insulin resistance increased during treatment. No statistically significant differences in serum TG and HDL-cholesterol levels during GH therapy were found. Conclusion: The development of insulin resistance and carbohydrate metabolism impairment have the greatest manifestations during GH therapy in girls with TS. Monitoring the basic parameters of carbohydrate-lipid metabolism in girls with TS seems particularly important.

Adrenal insufficiency in patients with Prader-Willi syndrome.

The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth hormone secretion, excessive appetite and associated obesity, impaired body temperature regulation, and hypothyroidism. The syndrome is also related to an increased risk of central adrenal insufficiency, although its prevalence remains unknown. The results of the studies in which different methods of pharmacological stimulation were used do not provide conclusive outcomes. As a result, there are no clear guidelines with regard to diagnosis, prevention, or long-term care when adrenal insufficiency is suspected in patients with PWS. Currently, most patients with PWS are treated with recombinant human growth hormone (rhGH). It has been confirmed that rhGH therapy has a positive effect on growth, body composition, body mass index (BMI), and potentially on psychomotor development in children with PWS. Additionally, rhGH may reduce the conversion of cortisone to cortisol through inhibition of 11ß-hydroxysteroid dehydrogenase type 1. However, its influence on basal adrenal function and adrenal stress response remains unexplained in children with PWS. This paper reviews the literature related to the hypothalamic-pituitary-adrenal axis dysfunction in the PWS patient population with a focus on children.

Gender confirmation hormonal treatment use in young Polish transgender binary and non-binary persons.

INTRODUCTION: Gender confirmation hormonal treatment (GCHT) is a cornerstone of medical treatments for persistent gender dysphoria, which is expected and required by many transgender binary and non-binary individuals. Many protocols have been published, and the qualification process is guided by the World Professional Association for Transgender Health Standards of Care. The standards and other documents such as the Endocrine Society Clinical Practice Guideline provide gender confirmation hormonal care also for minors. However, the issue of starting these treatments in younger populations is still marked by controversy. This preliminary study aimed to inquire into GCHT (medications used, timing of its initiation, its tolerance, and sources of information on the treatment) in a convenience sample of young Polish transgender binary and non-binary persons. MATERIAL AND METHODS: A total of 166 adult transgender participants answered our online questionnaire between November 2020 and December 2021. The population was divided into 2 groups: assigned male at birth (AMB, n = 37) and assigned female at birth (AFB, n = 126). Subsequently, division into binary and non-binary was applied to these groups. RESULTS: Most patients (91.9% AMB and 92.2% AFB) did not use gender confirmation medical treatments before the age of 18 years. The most common medication used for GCHT before the age of 18 was cyproterone acetate for AMB and testosterone for AFB. When asked about their opinion on the timing (age) of initiating GCHT, 73.1% of the AMB and 59.2% of the AFB participants shared the view that it had been initiated much too late. By far the most common source of information on GCHT and gender confirmation surgery (GCS) was the Internet (92.2%). CONCLUSIONS: These treatments (including pubertal blocking) seem to be rarely commenced in Poland before the age of 18 years. In adults, treatment consists mostly of either testosterone or oestradiol, and cyproterone acetate and, more seldom, spironolactone are used as antiandrogens in persons assigned male at birth. In turn, gonadotropin-releasing hormone agonists are barely used at all. Specialists need to be more aware that withholding treatment in minors with gender dysphoria is not a health-neutral option. Gonadotropin-releasing hormone agonists should also be more often considered as an alternative to cyproterone acetate in the context of long-term safety.

Questions concerning fertility preservation during transition in girls with Turner syndrome: review of the literature.

Loss of fertility is one of the most important concerns facing Turner syndrome (TS) patients as they transition into adult health care. Due to the limited and rapidly decreasing ovarian reserve, many TS patients require fertility preservation (FP) techniques to preserve their reproductive potential until they are ready to pursue procreation. One has to also remember about the additional risks connected with pregnancy in TS patients. In order to determine the optimal time for introducing FP techniques and decrease the chance of an unnecessary intervention, markers and procedures assessing ovarian reserve have been developed. The exposure to potential cardiovascular complications should be determined before FP to avoid unnecessary procedures in patients with potential contraindications to pregnancy. The aim of the present review is to answer the following three questions important for successful preservation of fertility and safe pregnancy in TS: which markers of ovarian reserve should be used as selection criteria for FP? Which methods of FP are the safest and most effective? Are there any cardiovascular contraindications to FP? For each of those questions, separate literature searches have been conducted. A total of 86 articles have been included in this review: 34 for the first question, 35 for the second, and 17 for the third. Ovarian reserve markers and cardiovascular contraindications to pregnancy should be established before FP; hoverer, there are no unambiguous indicators as to which patients should be disqualified from the FP and more evidence is needed in this subject.

The relationship between the level of vitamin D, leptin and FGF23 in girls and young women with polycystic ovary syndrome.

Polycystic ovary syndrome is an endocrinopathy that mainly affects adolescent girls and young women of childbearing age. In girls, the presence of clinical and biochemical symptoms of hyperandrogenism should be particularly considered. The role of vitamin D deficiency in insulin resistance, inflammation, dyslipidemia, and obesity, i.e. in diseases associated with PCOS, has been investigated, which may suggest its involvement in the pathophysiology of the syndrome. Leptin has been shown to stimulate the formation of FGF23 in bones. There is a relationship between the incidence of dyslipidemia, adipose tissue mass and the concentration of fibroblast growth factor 23. The main aim of the presented research project is to assess the concentration of vitamin D, calcium, and selected hormones as well as the concentration of adipokines (leptin) in girls diagnosed with polycystic ovary syndrome. Materials and methods: The study included a population of 85 girls and young women aged 14 to 22 years. The study group included 37 girls who were diagnosed with polycystic ovary syndrome according to the modified Rotterdam's criteria. The control group consisted of 48 completely healthy girls. In the first stage of the study participants were required to answer background questions. Next, anthropometric measurements were performed. The laboratory tests assessed: leptin, FGF23, FSH, SHGB, total testosterone, DHEA-S, 25-OH-D3, PTH, calcium, androstadiene, AMH, glucose, insulin. Results: The vitamin D level in the group with polycystic ovary syndrome was lower than in the control group, but there was no statistically significant difference. The level of anti-Müllerian hormone was significantly higher in the group of girls diagnosed with PCOS compared to the control group. Statistically significant differences between both groups were also noted in the HOMA-IR value. The concentration of calcium, parathyroid hormone, FGF23 and leptin in the study and control groups showed no statistically significant difference. Conclusions: In the studied group of girls with PCOS, no correlation between the level of vitamin D and selected parameters such as: AMH leptin, HOMA-IR and FGF23 was confirmed. On this basis, it can be assumed that additional vitamin D supplementation would not reduce the symptoms of polycystic ovary syndrome.

A tendency to worse course of multisystem inflammatory syndrome in children with obesity: MultiOrgan Inflammatory Syndromes COVID-19 related study.

Background: A new disease entity called multisystem inflammatory syndrome in children (MIS-C) is a rare consequence of COVID-19 infection. The pathophysiology and risk factors of MIS-C are still unclear, and the clinical manifestation ranges from milder forms to cases needing intensive care unit treatment. Based on available data, obesity is linked to pro-inflammatory stimulation. Moreover, several studies showed that obesity could play a role in COVID-19 severity and its comorbidities among the adult and children's populations. This study aimed to investigate the influence of overweightedness/obesity in childhood for the course of MIS-C in Poland. Methods: This study presented data from the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR) collected between 4 March 2020 and 20 February 2021. Of the 371 patients that met the Polish MIS-C criteria, 306 were included for further analysis. Results: Children who are obese (OB with body mass index (BMI) ≥95th percentile) and overweight (OV with BMI ≥85th percentile but <95th percentile) (28 and 49 patients, respectively) represented 25.1% (n=77) of all recruited patients. Complete recovery at the time of discharge presented in 93% of normal body weight (NW) participants and 90% of OV children (p>0.05). Among OB children, 76% recovered fully, which differed from the NW group (p=0.01). Calculated odds ratio (OR) of incomplete recovery for OB children was 4.2. Irrespective of body weight, there were no differences (p>0.05) in the length of hospitalization and the duration of symptoms (for OB, 13 and 16.5 days; for OV and NW, 10 and 14 days, respectively), as well as in the frequency of cardiovascular abnormalities, necessity of oxygen therapy (OB, 26.9%; OV, 23.9%; and NW, 20.7%), and intravenous immunoglobulin and glucocorticosteroid (GCS) treatment. Conclusion: The higher risk of incomplete recovery and observed tendency toward a worsening course of MIS-C in patients with obesity suggest the need for further studies to confirm and understand our findings.

Effect of Growth Hormone Treatment on the Concentration of Selected Metabolic Markers in Girls With Turner Syndrome.

Background: As Turner syndrome (TS) predisposes to obesity and metabolic disorders, and their complications, such as cardiovascular diseases, are the main causes of shortened life expectancy in patients with TS, new metabolic markers that could serve as early predictors of dysmetabolic state are sought. Objective: Assessment of MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) before the onset of growth hormone (GH) therapy and then during GH treatment as well as markers assessment during GH medication in girls with TS to establish marker stability and repeatability, and the impact of GH on markers concentration. Method: The concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF, and VEGF were measured in nine girls with TS before the onset of GH therapy and then after at least 3 months of treatment period. Subsequently, markers concentration was determined in 17 girls during GH medication, with the first determination after at least a 3-month treatment period. The patients' clinical and biochemical phenotypes were determined by weight, height, BMI, total cholesterol, HDL cholesterol, triglycerides, and glucose concentration. Results: Comparison of markers concentration revealed a significantly higher concentration of MMP-2 in patients undergoing GH treatment (132.1 ± 42.05) than before the onset of therapy (105.0 ± 45.5, p=0.045). The values of the first measurement of VEGF in girls with TS undergoing GH therapy were significantly higher than those during the second measurement (30.9 ± 33.4 vs. 12.5 ± 11.7, p=0.029). There were no statistically significant differences between the measurements of the remaining markers concentration at any stage of the analysis. Conclusion: Increase in MMP-2 concentration is visible during GH therapy in comparison to the pre-GH period in girls with TS which demands confirmation in subsequent tests. The role of VEGF requires further studies in the context of carbohydrate-lipid disturbances in girls with TS and its association with GH treatment.

Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland.

Short stature resulting from SGA is an obligatory indication for treatment with rhGH. The aim of the study was to assess the response to rhGH treatment in patients treated in the years 2016−2020 in six clinical centers in Poland. During the analysis, auxological data were collected, and anthropometrical parameters (Ht, SDS Ht, HV and ΔHV) were reassessed. Subgroups of patients with dysmorphic features (DYSM), fetal alcohol syndrome (FAS) and Silver-Russel syndrome (SRS) were selected. The study group consisted of 235 children (137 boys). The medium initial age was 9.08 years, and 190 patients were in the prepubertal stage. The poor response to treatment was defined as ΔHt SDS < 0.3 and/or ΔHV < 3 cm/year. Seventeen per cent of all patients after the first year and 44% after the second year met the ΔHt SDS < 0.3 criterion, and 56% during the first and 73% during the second year met the ΔHV < 3 cm/year criterion. Our data suggest that patients with SRS may show the best response to treatment, which was sustained throughout the follow-up period. The best response in all subgroups was observed during the first 12 months of therapy. Although the proportion of patients meeting the poor response criteria was high, only a few patients exceeded the 97th percentile for IGF-1 concentration during the first year of treatment. This might suggest that increasing the dose of rhGH in the second treatment year in order to sustain accelerated HV would be safe in these patients.

Diagnosis and treatment of thyroid cancer in adult patients - Recommendations of Polish Scientific Societies and the National Oncological Strategy. 2022 Update [Diagnostyka i leczenie raka tarczycy u chorych doroslych - Rekomendacje Polskich Towarzystw Naukowych oraz Narodowej Strategii Onkologicznej. Aktualizacja na rok 2022].

The guidelines Thyroid Cancer 2022 are prepared based on previous Polish recommendations updated in 2018. They consider international guidelines - American Thyroid Association (ATA) 2015 and National Comprehensive Cancer Network (NCCN); however, they are adapted according to the ADAPTE process. The strength of the recommendations and the quality of the scientific evidence are assessed according to the GRADE system and the ATA 2015 and NCCN recommendations. The core of the changes made in the Polish recommendations is the inclusion of international guidelines and the results of those scientific studies that have already proven themselves prospectively. These extensions allow de-escalation of the therapeutic management in low-risk thyroid carcinoma, i.e., enabling active surveillance in papillary microcarcinoma to be chosen alternatively to minimally invasive techniques after agreeing on such management with the patient. Further extensions allow the use of thyroid lobectomy with the isthmus (hemithyroidectomy) in low-risk cancer up to 2 cm in diameter, modification of the indications for postoperative radioiodine treatment toward personalized approach, and clarification of the criteria used during postoperative L-thyroxine treatment. At the same time, the criteria for the preoperative differential diagnosis of nodular goiter in terms of ultrasonography and fine-needle aspiration biopsy have been clarified, and the rules for the histopathological examination of postoperative thyroid material have been updated. New, updated rules for monitoring patients after treatment are also presented. The updated recommendations focus on ensuring the best possible quality of life after thyroid cancer treatment while maintaining the good efficacy of this treatment.

The Clinical Picture of Patients Suffering from Hypophosphatasia-A Rare Metabolic Disease of Many Faces.

Hypophosphatasia (HPP) is a rare, and usually diagnosed with delay, genetic disease caused by a mutation in the alkaline phosphatase liver/bone/kidney type (ALPL) gene. Low activity of the alkaline phosphatase (ALP) impairs the hydroxyapatite formation, reducing skeletal mineralization. The aim of the study was to present patients diagnosed with HPP. The data from the history and medical records of patients were analyzed. In the study group, one patient was diagnosed with perinatal type of HPP, three were diagnosed with infant variant, eight were diagnosed with children variant, two were diagnosed with odontohypophosphatasia, and two were diagnosed with the adult type of the disease. The most frequently presented symptoms included premature loss of teeth in 11/16 (68.75%) patients, bone deformities in 10/16 (62.5%) patients, chronic bone pain in 9/16 (56.25%) patients, and fractures in 8/16 (50%) patients. Reduction in bone mineral density in at least one examined projection has been found in 11/14 patients. Conclusions: The correct diagnosis of HPP is difficult due to the variety of types and clinical symptoms, as well as the very rare occurrence of this disease. Both lower and upper reference values of the determined biochemical parameters may be important in HPP diagnostics.

The prevalence of autoimmune thyroiditis in adolescent girls with polycystic ovary syndrome.

OBJECTIVES: Both polycystic ovary syndrome (PCOS) and autoimmune thyroiditis (AT) are reported to be common endocrinopathies. In recent years the number of publications assessing the coexistence of these two disease entities in adult women has been growing. There are many suggestions regarding pathophysiological mechanisms that can cause the relationship between AT and PCOS. However, there is still a lack of research among adolescent girls. The aim of the study was to analyze the occurrence of autoimmune thyroiditis in adolescent girls with PCOS. MATERIAL AND METHODS: The study group included 80 girls diagnosed with PCOS (chronological age: 16.54 ± 1.00 years, BMI: 22.80 ± 3.27 kg/m2), and the control group - 64 regularly menstruating girls (chronological age: 16.71 ± 0.63 years, BMI: 24.8 ± 5.2 kg/m2). The thyroid function and morphology were assessed based on the concentration of thyroid stimulating hormone (TSH), free thyroxine (fT4), anti thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) antibodies and ultrasound scan of the thyroid gland. RESULTS: AT was diagnosed in 18 (22.5%) girls from the study group and nine (14.06%) from the control group (p > 0.05). Positive anti-TPO titer was observed more often in the study group [21 patients (26.25%)] than in the control group [9 girls (14.06%)] (p = 0.054). Moreover, an abnormal ultrasound scan of the thyroid gland characteristic for AT was found in 18 girls from the study group (22.50%) and 8 girls from the control group (12.50%) (p > 0.05). CONCLUSIONS: The results of the analyzed studies do not confirm a significant relationship between PCOS and AT in adolescent girls. However, in the group of girls with PCOS, autoimmune process exponents were more frequent (anti-TPO), reaching the borderline level of statistical significance.

Brain-Derived Neurotropic Factor, Vascular Endothelial Growth Factor and Matrix Metalloproteinases as Markers of Metabolic Status in Non-Growth Hormone-Treated Girls With Turner Syndrome.

Background: Turner syndrome (TS) presents a high risk of congenital heart defects and may predispose to both obesity and related metabolic complications. Hence the search for new markers as potential early predictors of the metabolic syndrome (MetS) and cardiovascular diseases appears warranted. Objective: To assess MMP-1 (matrix metalloproteinase-1), MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metallopeptidase-9), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) in non-MetS TS girls not treated with growth hormone (GH) vs. healthy short stature girls, and to assess the connection with basic metabolic parameters. Method: The concentrations of circulating MMP-1, MMP-2, MMP-9, BDNF, GDNF and VEGF were measured in 12 patients with TS not treated with growth hormone. The control group was composed of 17 girls with non-pathologic short stature. The patients' clinical and biochemical phenotypes were determined by weight, height, total cholesterol, HDL cholesterol, triglycerides, glucose, aminotransferases, IGF1, TSH and fT4. Results: There were no differences in mean age, weight, BMI Z-Score, or hSDS between the studied group and the controls; however, they differed in baseline values of ALT (18.2 ± 4.2 vs. 14.2 ± 4.1, p= 0.02), BDNF [29951.5 (26176.9 - 41271.9) vs. 23131.7 (18392.4 - 28313.3), p=0.01] and MMP-2 [91.8 (71.7 - 111.0) vs. 143.6 (123.7 - 244.5), p< 0.001]. BDNF correlated with ALT activity (r = 0.56 p = 0.002) and BMI Z-score (r = 0.38 p = 0.042), while MMP-2 correlated with HDL concentration (r = 0.48 p = 0.029) in all the patients. The analysis of the study group alone revealed significant positive correlations between MMP-9 and TSH (r = 0.74 p = 0.036), BDNF and both ALT (r = 0.73 p = 0.038) and TSH (r = 0.85 p = 0.008), and a negative correlation between MMP-1 and fT4 (r = -0.75 p = 0.032). The control group did not present any significant correlations. Conclusion: The higher concentrations of BDNF and lower of MMP-2 found in girls with TS without MetS compared to healthy girls with short stature, could have a major impact on the future "natural" development of the metabolic status. Our findings need further studies.

Personalized approach to childhood obesity: Lessons from gut microbiota and omics studies. Narrative review and insights from the 29th European childhood obesity congress.

The traditional approach to childhood obesity prevention and treatment should fit most patients, but misdiagnosis and treatment failure could be observed in some cases that lie away from average as part of individual variation or misclassification. Here, we reflect on the contributions that high-throughput technologies such as next-generation sequencing, mass spectrometry-based metabolomics and microbiome analysis make towards a personalized medicine approach to childhood obesity. We hypothesize that diagnosing a child as someone with obesity captures only part of the phenotype; and that metabolomics, genomics, transcriptomics and analyses of the gut microbiome, could add precision to the term "obese," providing novel corresponding biomarkers. Identifying a cluster -omic signature in a given child can thus facilitate the development of personalized prognostic, diagnostic, and therapeutic approaches. It can also be applied to the monitoring of symptoms/signs evolution, treatment choices and efficacy, predisposition to drug-related side effects and potential relapse. This article is a narrative review of the literature and summary of the main observations, conclusions and perspectives raised during the annual meeting of the European Childhood Obesity Group. Authors discuss some recent advances and future perspectives on utilizing a systems approach to understanding and managing childhood obesity in the context of the existing omics data.