Objective: Clinical studies suggest that the thyroid autoantibodies and/or hypothyroidism are not present in Turner’s syndrome (TS) patients before the age of 8 years and are more frequent in patients with the X isochromosome. The aim of the study was to analyze the dynamics of thyroid dysfunction in girls with TS. Design: 86 TS patients with a median age of 10.6 years were followed for 4.6 ± 3.0 years. Outcomes: The prevalence of thyroid abnormalities increased from 25.5 to 50% during the follow-up. Finally, 31 (36%) patients had positive thyroid autoantibodies and 27 (31.4%) had subclinical hypothyroidism. Hashimoto’s thyroiditis was diagnosed in 15 patients. Median age of developing thyroid antibodies and subclinical hypothyroidism was 14.1 and 14.8 years, respectively. The youngest hypothyroid patient was 1.8 years old and the youngest girl with positive anti-thyroid antibodies was 5.5 years old. Autoantibodies appeared mainly after the age of 13. The risk of developing subclinical hypothyroidism was greatest between 12 and 14 years of age. The prevalence of thyroid abnormalities was not related to the karyotype. Conclusions: Thyroid autoimmunity and dysfunctions in TS may start early, their prevalence increases with age, independently of karyotype and without any clinical symptoms and signs.

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ObjectiveThe 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.MethodsThe 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-β), 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.ResultsThe 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).ConclusionTS 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.

For Turner syndrome (TS) patients, smooth transition from pediatric to adult health care is a critical point. The study objective was to evaluate the medical follow-up of young women with TS in one clinical center 3 years after the latest guidelines had been introduced by the TS Study Group. A questionnaire study was performed in 59 TS adults selected from a database of 117 patients. Twenty-two of them, aged 23.0 ± 2.8 years, consented to participate. Nineteen responders (86.4%) were followed up by general practitioners who were not aware of the TS diagnosis in 14 (63.6%) cases. Eight (36.4%) were seen regularly by the relevant specialists. Adequate medical assessment varied from 5% (celiac serology) to 74% (gynecology assessment) and 82% (ear-nose-throat) of participants. None of the patients had undergone all of the recommended investigations according to recommendation. Height deficiency, body mass index, age at TS diagnosis and level of education did not correlate with the number of assessments performed (p = 0.687, p = 0.810, p = 0.641, and p = 0.568, respectively). Three years after the introduction of the current guidelines, medical follow-up in the transition phase is still inadequate. Improvement in transitional health care is warranted through better patient education, referring to physicians caring for adults with TS and better cooperation with general practitioners with wider popularization of the TS recommendations among them.

ObjectiveEstrogen 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.MethodsThe 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.ResultsThe 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).ConclusionThe 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.

IntroductionCalcitonin (Ct) and carcinoembrional antigen (CEA) are widely used as tumor markers for the post-operative follow-up of patients with medullary thyroid carcinoma (MTC).In patients with elevated serum Ct and CEA their dynamics can be described by calculating the doubling time (DT) - the time, they need to double the serum concentration. Previous reports concluded that the Ct and CEA DT have prognostic value in MTC patients.Patients and methodsWe retrospectively analyzed data of 70 MTC patients with elevated serum Ct or CEA. In total, doubling times were calculated and the DT of the less favorable marker was used to stratify the patients into the low- and high-risk group with the cut-off value of 2 years. The survival analysis was performed using Cox proportional hazard method.ResultsThe doubling time < = 2 years of the less-favorable marker had significant prognostic impact for recurrence-free survival, HR = 2.61 (1.43-4.71) and overall survival, HR = 8.99 (3.51-23.04).ConclusionsThe calcitonin and carcinembrional antigen doubling times of less than two years are negative prognostic factors for MTC recurrence-free and total survival in patients with persistent or recurrent disease. They may be used as predictive factors for more intensive search of disease localization in asymptomatic hypercalcitoninemia and for therapy choice in symptomatic disease.

Aim: Although recombinant human thyrotropin (rhTSH) is widely used in treating differentiated thyroid cancer (DTC), almost all clinical investigation has been in adults. The aim of our retrospective study was to evaluate outcomes of adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and to compare them to 131 I therapy during L-thyroxin withdrawal (THW). Methods: Patients with the diagnosis of DTC who were %18 years of age and had no signs of persistent disease at the time of 131 I treatment were included; 48 patients were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of follow-up after therapy was 67 months and was longer in the THW group (99 vs 43 months, P!0.05).Results: On the day of 131 I administration, all but one patient had TSH levels above 25 mIU/ml. Peak TSH concentration was significantly higher in the rhTSH group (152 mIU/ml vs 91 mIU/ml). Similarly, the thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8 ng/ml). No side effects requiring medical intervention were recorded after rhTSH administration. The evaluation of disease outcomes during TSH stimulation (6-18 months after 131 I treatment) revealed equal rates of thyroid ablation (71%) in both groups. During subsequent follow-up, five patients showed recurrence (PO0.05). Conclusions: In children/adolescents, rhTSH-aided adjuvant radioiodine treatment is associated with rates of remnant ablation and short-term recurrence similar to THW. As this preparation has several advantages over THW, rhTSH may become the preferred method of TSH stimulation once studies of long-term outcomes show non-inferiority to THW in this age group.

Medullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs as a sporadic form. It is well known that RET mutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type of RET gene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of the RET gene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.