Background: Turner Syndrome is associated with an increased risk of autoimmune diseases, such as autoimmune thyroiditis, coeliac disease, type 1 diabetes mellitus, inflammatory bowel disease, alopecia areata, or vitiligo. The presence of isochromosome iXq and exposure to estradiol may contribute to the development of the autoimmune process. The aim of this study was to determine the prevalence of autoimmune diseases in a group of TS patients and to assess the impact of karyotype and puberty on the development of autoimmune diseases. Patients and Methods: The analysis encompassed clinical and biochemical data of 134 patients treated between 2001 and 2018. All the patients were examined for autoimmune disease symptoms and tested for the presence of antithyroperoxidase (anti-TPO) and antithyreoglobulin (anti-TG) antibodies. In 73 of the patients, anti-transglutaminase (anti-tTG) antibodies were measured. Thyroid function was assessed by measuring TSH and fT4 levels. Results: The mean follow-up was 5.7 ± 3 years. An autoimmune disease was diagnosed in 46 (34.3%) patients: 39 (29.1%) had only one disorder, whilst 7 (5.2%) presented two disorders. The most common disorder, observed in 40 (29.9%) patients, was thyroid autoimmunity. Hashimoto disease was diagnosed in 20 (14.9%) patients. Of the 73 patients tested for coeliac disease, 4 (5.5%) had anti-tTG and 2 (2.7%) presented overt coeliac disease. Vitiligo was diagnosed in 3 (2.2%) patients, type 1 diabetes mellitus or psoriasis were diagnosed in 2 (1.5%) patients, whilst alopecia areata or lichen sclerosus were diagnosed in 1 (0.7%) patient. The impact of karyotype or estradiol exposure on developing autoimmune diseases were not statistically significant. Conclusions: Our study showed a higher incidence of autoimmune diseases in TS, which is in line with the literature; however, the impact of iXq, or spontaneous/inducted puberty was not confirmed.

Background Turner syndrome (TS) predisposes an individual to obesity and related metabolic disorders. As the TS population is at a higher risk of cardiovascular diseases and malformations, research into laboratory markers of metabolic complications has been ongoing. Special significance has recently been attributed to matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and neurotrophic factors, such as BDNF and GDNF. Objective To establish whether cardiometabolic risk in patients with TS is reflected in the concentrations of metalloproteinases and neurotrophic factors. Method The concentrations of circulating MMP-1, MMP-2, MMP-9, TIMP-1, BDNF, GDNF, and VEGF were measured in 17 patients with TS. The control group was composed of 11 girls with nonpathologic short stature and normal karyotype. Results There were no differences in chronological or bone age. No significant differences were observed in mean weight, although the Z-score BMI was higher in the study group. The mean baseline values of MMP-1 and BDNF were significantly lower in the control group than in the study group (p < 0.001, p = 0.001). Regression analysis revealed a positive correlation between MMP-1 concentrations and Z-score BMI (r = 0.36, p = 0.047) and between BDNF and Z-score BMI (r = 0.48, p = 0.013). Conclusion Our pilot study showed that MMP-1 may be a potential indicator of a higher risk of cardiometabolic complications in girls with TS. The elevated concentrations of BDNF in normal-weight girls with TS need to be studied further, taking into consideration the influence of estrogen-androgen imbalance.

BackgroundTurner 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.ObjectiveTo 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.MethodThe 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.ResultsThere 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&lt; 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.ConclusionThe 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.

Congenital cardiovascular structural abnormalities, hypertension, low birth weight, increased prevalence of obesity, frequent glucose intolerance and dyslipidemia are risk factors of premature mortality for cardiovascular events in Turner syndrome (TS). The life expectancy in TS is reduced by at least 10 years and the risk of premature death is increased 3-fold compared to general female population. Hormonal therapy in TS, both estrogens in different algorithms and growth hormone in supraphysiological dose, may additionally modify these factors. In this review we summarize cardiometabolic markers potentially present in girls and women with TS.

BackgroundComponents 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.ObjectiveTo 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 method89 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.ResultsObesity 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 &lt; 0.001; pV0-V3 = 0.006; pV0-V5 &lt; 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.ConclusionThe 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.

BackgroundAs 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.ObjectiveAssessment 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.MethodThe 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.ResultsComparison 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.ConclusionIncrease 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.