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.

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.

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.

Metabolic and Hormonal Profile of Adolescent Girls With Polycystic Ovary Syndrome With Concomitant Autoimmune Thyroiditis.

Introduction: Both polycystic ovary syndrome (PCOS) and autoimmune thyroiditis (AT) are considered to be among the most common endocrinopathies in young women, and they are classified as diseases that affect many processes in the human body. Their role in the development of metabolic disorders and diseases of the cardiovascular system in adult women is also emphasized. However, there are no data available to assess such risk in the teenage girl population. The aim of the study was to assess the hormonal and metabolic profile of adolescent girls with PCOS, additionally diagnosed with AT, as well as to identify possible risk factors for the coexistence of AT and PCOS. Material and Methods: 80 euthyroidic PCOS patients were qualified for the study (chronological age 16.54 ± 1.00 years, BMI 24.60 ± 4.16 kg/m2). Eighteen girls diagnosed with AT were included in the study group and 62 girls without AT-in the control group. Each patient had biochemical and hormonal tests performed. Additionally, to diagnose AT, the level of antibodies against thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG), as well as the image of the thyroid gland on ultrasound examination, were taken into account. Results: Estradiol concentration was significantly higher in the study than in the control group (203.00 ± 217.00 vs. 152.00 ± 78.50 pmol/L, p=0.02). Higher DHEAS concentrations were also observed in the AT group compared with the group without AT (391.28 ± 176.40 vs. 317.93 ± 114.27 µg/dl, p=0.04). Moreover, there was a positive correlation between AT and estradiol concentration (ry=0.27; p=0.04). It was also shown that there is a tendency toward statistical significance for the positive correlation between the positive anti-TPO titer and the glucose concentration at 120 min OGTT (rÆ´=0.26; p=0.07) and girls with PCOS and AT had higher glucose levels in 120 min OGTT (115.29±41.70 vs. 98.56±28.02 mg/dl, p=0.08). Conclusion: The study results showed no difference in the metabolic profile between the groups. The high concentration of estradiol found in girls with PCOS and AT may indicate the role of this hormone in the development of the autoimmune process. However, the numbers are small, and more research is needed to confirm our findings.

Depression, anxiety and self-esteem in adolescent girls with polycystic ovary syndrome.

OBJECTIVES: Objective of the study was to evaluate the depression, anxiety and perceived stress level in adolescent girls with diagnosed polycystic ovary syndrome (PCOS), as well as to assess their body and self-esteem and its impact on emotional status. MATERIAL AND METHODS: In 27 adolescent girls with confirmed diagnosis of PCOS (study group) as well as 27 healthy, regularly menstruating, age and BMI matched girls (control group) Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale-10 (PSS-10), Rosenberg Self-Esteem Scale (RSES) and Body-Esteem Scale (BES) containing three subscales (sexual attractiveness, weight concern, physical condition) were performed. RESULTS: There were no significant differences between PCOS group and control group in depression and PSS-10 scores, but the anxiety score was significantly higher in control than in PCOS group (9.6 ± 3.0 vs 7.3 ± 3.9, p = 0.02). Moreover, in BES subscales' scores there were no significant differences between the groups, whereas RSES score was significantly higher in PCOS group (25.0 ± 7.1 vs 28.3 ± 4.6, p = 0.04). In PCOS group anxiety score was related to PSS-10 score (r = 0.56, p = 0.005). Moreover, we found that obesity was negatively related to anxiety (rÆ´ = -0.4, p = 0.04), depression (rÆ´ = -0.48, p = 0.02), PSS-10 (rÆ´ = -0.59, p = 0.004) and physical condition scores (rÆ´ = -0.44, p = 0.04). In girls with PCOS the more severe depression the worse weight control (rÆ´ = -0.56, p = 0.04). CONCLUSIONS: We conclude that in adolescent girls PCOS is not related to anxiety and depressive symptoms as well as poor self-esteem.

Immunological Profile and Predisposition to Autoimmunity in Girls With Turner Syndrome.

OBJECTIVE: The risk of autoimmune diseases (AD) in patients with Turner Syndrome (TS) is twice higher than in the general female population and four times higher than in the male population. The causes of the increased incidence of AD in TS are still under discussion. We hypothesized the presence of a specific humoral, cellular, and regulatory T cell (Treg) immunity profile which predisposes to AD, disorders of immunity, and disorders of immune regulation. METHODS: The study encompassed 37 girls with TS and with no signs of infection. The control group included 11 healthy girls with no hormonal disorders. A medical history focused on AD and immunity disorders was taken from all participants. The levels of: immunoglobulins IgG, IgA, IgM, total lymphocytes, lymphocytes subpopulations CD3+, CD4+, CD8+, CD19+, natural killer cells, Treg cells (CD4+ CD25+ CD127- FOXP3+), anti-inflammatory cytokines (interleukin-10, transforming growth factor-ß), anti-nuclear antibodies, glutamic acid decarboxylase (GAD65 Abs), anti-thyroid peroxidase (anti-TPO Ab), and anti-thyroglobulin (anti-TG Ab) autoantibodies were determined in each participant. RESULTS: The mean age and BMI in the TS group and in controls were comparable (11.9 ± 4.1 vs. 12.5 ± 4.0 years; 19.2 ± 3.4 vs. 19.7 ± 4.6, p > 0.05). Mean hSDS was significantly higher in controls (-2.2 ± 0.9 vs. -0.4 ± 1.5, p < 0.0001). AD and recurrent otitis media with complications were previously confirmed in 9 (24.3%) and 10 (27.0%) girls with TS. The TS group had significantly lower levels of IgG (p = 0.02), lower%CD4 (p < 0.001) and a significantly lower CD4:CD8 ratio than the controls (p < 0.001). There were no differences in mean Treg% between girls with TS and healthy controls. However, comparing Treg% between the TS group with coexisting autoimmunity and the remaining participants, a statistically significant difference was observed (2.09 ± 0.5 vs. 2.77 ± 1.6, p = 0.048). Patients with iXq had lower CD4% and more frequently had positive anti-TPO Ab and anti-TG Ab compared to the remaining girls with TS and controls (p = 0.001, p < 0.001, p = 0.01). CONCLUSION: TS predisposes to AD, especially if associated with coexisting iXq. Our preliminary findings show that patients with TS may present a specific profile of humoral and cellular immunity markers, different from healthy girls.

Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls-A Longitudinal Study.

OBJECTIVE: Estrogen replacement therapy (ERT) for Turner syndrome (TS) is a widely discussed topic; however, the optimal model of ERT for patients with delayed diagnosis and/or initiation of therapy is still unclear, mainly due to insufficient data. We present the results of a prospective observational single-center study in which the efficacy of late-onset puberty induction by one-regimen transdermal ERT in TS girls was evaluated. METHODS: The analysis encompassed 49 TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified transdermal ERT protocol was used for puberty induction (first two months 12.5 µg/24 h, thereafter 25.0 µg/24 h until breakthrough bleeding). Clinical visits for examination and therapy modification took place every 3-6 months. Transabdominal pelvic ultrasound examinations were performed at least twice: at the beginning and at the end of follow-up. RESULTS: The mean (SD) age at ERT induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years. Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4 after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier initiation of ERT (≤14 years), B2 (p = 0.059) was achieved faster and B4 (p = 0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%) patients had at least stage B3 at menarche. The karyotype, initial weight, and body mass index had no impact on puberty tempo during ERT. The uterine volume increased significantly during ERT in all the study group (p < 0.0001), and in half of the patients, the increase was at least 12.4-fold. It did not correlate with the duration of treatment (p = 0.84) or the dose of estradiol per kilogram (p = 0.78), nor did it depend on karyotype (p = 0.71) or age at ERT initiation (p = 0.28). There were no differences in ΔhSDS during ERT (p = 0.63) between the two age groups (ERT ≤14 and >14 years). CONCLUSION: The presented easy-to-use fixed-dose regimen for late-onset puberty induction allowed for a satisfactory rate of achieving subsequent puberty stages and did not influence the growth potential.

Prediction of Spontaneous Puberty in Turner Syndrome Based on Mid-Childhood Gonadotropin Concentrations, Karyotype, and Ovary Visualization: A Longitudinal Study.

AIMS: To investigate whether karyotype, mid-childhood (6-10 years) follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and ultrasound ovary visualization results can be used as indicators of spontaneous puberty in Turner syndrome (TS). METHODS: The analysis was based on clinical and biochemical data from 110 TS girls aged >13 years at the end of the study (1,140 visits between 1996 and 2015). The study population was divided according to karyotype: 45,X and non-45,X. RESULTS: The mean age ± standard deviation at diagnosis was 10.7 ± 4.0 years, and the follow-up duration was 5.9 ± 3.3 years. Spontaneous puberty was confirmed in 48% and menarche in 20% of the subjects, less frequently in 45,X girls. The mean age at Tanner stage B2 was 13.7 ± 2.4 years and that at menarche 14.2 ± 1.7 years, regardless of the karyotype. The median FSH level at 6-10 years was 8.16 IU/L, which was significantly lower than <6 years and >10 years. The median LH level at 6-10 years was 0.35 IU/L, which was lower than >10 years. The chance of spontaneous menarche was decreased in girls with FSH ≥6.7 IU/L between 6 and 10 years. CONCLUSIONS: Although spontaneous puberty and menarche occur more frequently in non-45,X girls, the karyotype cannot be used to predict them. However, the chance of spontaneous menarche can be predicted based on gonadotropin cut-off values. There was no correlation between ultrasound ovary visualization results and spontaneous puberty.