Aspasia Fotinou

Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus.

Abstract Introduction. Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). Aims. We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD). Materials and methods. We studied 144 children and adolescents with T1DM. Their age was 12.3 ± 4.6 (mean ± SD) years, and duration of diabetes was 4.6 ± 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay. Results. The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 μIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09–1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7–2350.3), and 3) older age (OR 22.9, 95% CI 1.13–463.2). Conclusions. Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.

The prevalence and risk factors for coeliac disease among children and adolescents with type 1 diabetes mellitus

AIMS Our aim was to determine in children with T1DM the prevalence of positive antibodies against tissue transglutaminase (anti-tTG IgA) as indices of coeliac disease (CD), as well as its clinical presentation, its determinants and its association with thyroid (anti-TG, anti-TPO) and pancreatic b-cell autoimmunity (anti-GAD). METHODS The study included 105 children and adolescents with T1DM, aged (mean±SD) 12.44±4.76 years, with a T1DM duration of 4.41±3.70 years. RESULTS Fifty of our patients (47.6%) were positive for anti-GAD, 9/105 (8.6%) for anti-tTG IgA and 21/105(20%) for anti-thyroid antibodies. The anti-tTG IgA (+) children, in comparison with the rest of the study population, were of younger age (9.31 vs. 12.74 years, p=0.038), shorter diabetes duration (2.16 vs. 4.62 years, p=0.056) and had mild growth impairment (height SDS: -0.55 vs. +0.20, p=0.055). Univariate logistic regression analysis revealed that the presence of anti-tTG IgA (+) was associated with younger age and shorter T1DM duration. Only 5/9 (55.6%) children with high titres of anti-tTG IgA developed mild gastrointestinal symptoms or growth retardation and had histological findings typical of CD. CONCLUSIONS The prevalence of anti-tTG IgA positivity among T1DM children was 8.6% and its occurrence was associated with younger age and short diabetes duration. Since CD presents in T1DM patients asymptomatically or with non-specific symptoms, periodic autoantibody screening is necessary for its early diagnosis.

Treatment with Thyroxine Reduces Thyroid Volume in Euthyroid Children and Adolescents with Chronic Autoimmune Thyroiditis

Background/Aims: Treatment with thyroxine in children with chronic autoimmune thyroiditis (AT) is controversial. The aim of this study is to investigate, by using thyroid ultrasonography, whether thyroxine influences thyroid volume in non-goitrous euthyroid children with AT. Methods: We studied 50 euthyroid non-goitrous children and adolescents with AT for 2 years by thyroid function tests and ultrasonography; 25 were randomized to receive thyroxine and 25 did not receive treatment. Median (IQR) age was 12.1 (11.1–13.2) years. Results: At baseline there was no difference in thyroid volume SDS between the two groups (treatment group 1.1 (0.7–1.5) and controls 0.9 (0.4–1.4), respectively). After 2 years the treatment group had lower thyroid volume SDS compared to the controls (0.6 (0.3–1.0) vs. 2.0 (1.1–2.3), p = 0.001). One child of the treatment group and 12 of the control group developed goiter. Two control children developed subclinical hypothyroidism. Within the treatment group, thyroid volume SDS was lower after 2 years of treatment (p = 0.002). Within the control group, thyroid volume SDS and TSH levels increased after 2 years of follow-up (p = 0.016, 1.9 (1.5–2.8) vs. 3.2 (2.4–4.4) mIU/ml, p = 0.006, respectively). Conclusions: Treatment with thyroxine reduces thyroid volume in non-goitrous euthyroid children with AT and may prevent goiter development.

Gastric Autoimmunity in Children and Adolescents with Type 1 Diabetes: A Prospective Study

Background/Aims: Type 1 diabetes (T1DM) is associated with gastric autoimmunity, which is characterized by the presence of parietal cell antibodies (APCA). We investigated gastric autoimmunity prevalence in T1DM children, its manifestations, determinants and association with thyroid gland (anti-Tg, anti-TPO) and pancreatic β-cell autoimmunity (anti-GAD) at baseline and 4 years later. Methods: The initial cohort (D1) included 97 children with T1DM. At follow-up after 4 years (D2), 84.5% of participants were evaluated. We assessed APCA, anti-Tg, anti-TPO, and anti-GAD presence, as well as symptoms of gastritis. APCA-positive patients were evaluated with gastrin, B12, ferritin levels and were submitted to gastroscopy. Results: Thyroid antibody positivity was increased among the APCA-positive patients. Four years later, among initially APCA-positive patients, 2/6 became APCA negative, while 4/6 developed high titers of APCA. On gastroscopy, 2 patients had chronic hypertrophic gastritis and one Helicobacter pylori gastritis. Conclusions: Gastric autoimmunity was associated with thyroid autoimmunity and anti-GAD persistence. After 4 years, the majority of APCA-positive patients developed high titers of APCA and mild symptoms of gastritis. Thus, patients with T1DM, and in particular those with thyroid and/or pancreatic autoimmunity, should have periodic autoantibody screening for the early diagnosis and follow-up of gastric autoimmunity.

Gonadal function of young patients with beta-thalassemia following bone marrow transplantation

Bone marrow transplantation (BMT) can induce short- and long-term impairment of gonadal function. Patients with beta-thalassemia represent a special group, as their primary diagnosis and its treatment modalities are responsible for gonadal dysfunction. To address the effect of BMT on puberty and gonadal function, we investigated 25 patients (12 males) with thalassemia who received allogenic BMT during childhood or adolescence and at the post-transplant evaluation were at an age that the pubertal process should have started. Pubertal stage by Tanner of breast and pubic hair, as well as testicular volume were assessed pre-BMT once and post-BMT at least twice. Menstrual history was recorded. FSH, LH, testosterone and estradiol levels were also determined. The impact of BMT appears to be different in the two sexes. Males seem to have higher tolerance, as all males who were pubertal at the time of BMT had normal testosterone, and all but one normal gonadotropin levels. From those who were prepubertal at BMT, 62% proceeded to normal pubertal development. Post-menarcheal females seem to be an extremely sensitive group to the deleterious effect of the transplantation process, as 100% of the post-menarcheal females exhibited amenorrhea and elevated gonadotropin levels. These findings are important for pre- and post-BMT counseling.

Tumor necrosis factor-α levels in short children

Growth hormone has been suggested to modulate the release of cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1). Moreover, TNFalpha synthesis has been shown to be decreased in hypophysectomized rodents. The aim of this study was to evaluate the influence of GH status on TNFalpha levels in a group of 44 short prepubertal children. Among them, 13 children aged 9.8 +/- 3.5 years were growth hormone (GH) deficient and the other 31 short children had normal growth velocity, normal GH response to provocative testing, and did not suffer from any chronic disease, thus this group was diagnosed as having idiopathic short stature (ISS). A group of 40 age- and sex-matched healthy children was used as controls. No significant differences in basal TNFalpha levels (pg/ml) were found between the GH deficient, ISS children and healthy controls. Furthermore, there was no correlation between TNFalpha and basal serum concentrations of GH or peak GH levels after stimulation. Similarly, TNFalpha values did not correlate with either IGF-I or IGFBP-3 serum concentrations.

Effect of GH Treatment on Coagulation Parameters in Children with Growth Hormone Deficiency

Objectives: To investigate the effect of GH administration on coagulation/fibrinolysis in GHD children before and after GH replacement. Methods: Fifteen prepubertal children, (mean age±SE: 9.8±0.4 years) with growth hormone deficiency (GHD) were included in this hospital based prospective study. Serum levels of PT, APTT, fibrinogen, VII, VIII, antithrombin (AT), protein C (PC), D-dimers, plasminogen (Plg), PAI-1 and a2antiplasmin (a2P) were measured before and after rhGH treatment. Control values were obtained from thirteen healthy subjects matched by age, sex and BMI. Results: At baseline all studied parameters were within normal ranges. However, PT and AT levels were significantly lower [(12.1±0.1 vs 12.5±0.04sec, p=0.04) and (117.3±3.1 vs 128.7±3.2%, p=0.024) respectively], and VIII, PAI-1 and a2P levels significantly higher compared to healthy controls [(122.6±6.1 vs 82.6±6.1%, p=0.001), (2.9±0.1 vs 1.3±0.3U/ml, p=0.001) and (119.1±1.0 vs 105.2±2.0%, p=0.001) respectively]. After a mean (SE) interval of 9.3 (0.4) months of treatment, a significant increase in PT and AT values was noted [(12.5±0.23 vs12.1±0.15sec, p=0.034) and (123.2±2.6 vs 117.3±3.1%, p=0.052) respectively]. PAI-1 levels were significantly decreased (2.3±0.3 vs 2.9±0.1U/ml, p=0.001) Conclusions: GH replacement therapy led to a significant increase in PT and AT levels and significant decrease in PAI-1 levels in GHD children, suggesting a beneficial effect of GH treatment against the possible risk of future atherothrombosis. Received: Apr 10, 2018 Accepted: May 28, 2018 Published: June 22, 2018 Copyright:

Cortisol response to adrenocorticotropin testing in non-classical congenital adrenal hyperplasia (NCCAH).

Abstract Background: The adequacy of cortisol response in non-classical congenital adrenal hyperplasia (NCCAH) has not been fully elucidated. The aim was to evaluate cortisol response to adrenocorticotropin (ACTH) stimulation test in children and adolescents with NCCAH and heterozygotes for CYP21A2 gene mutations. Methods: One hundred and forty-six children and adolescents, mean age 7.9 (0.7–17.5) years with clinical hyperandrogenism, were evaluated retrospectively. Thirty-one subjects had NCCAH, 30 were heterozygotes for CYP21A2 gene mutations, while 85 showed normal response to ACTH test. Results: Baseline cortisol levels did not differ among NCCAH, heterozygotes, and normal responders: 15.75 (5.83–59.6) μg/dL vs. 14.67 (5.43–40.89) μg/dL vs. 14.04 (2.97–34.8) μg/dL, p=0.721. However, NCCAH patients had lower peak cortisol compared to heterozygotes and control group: 28.34 (12.25–84.40) vs. 35.22 (17.47–52.37) μg/dL vs. 34.92 (19.91–46.68) μg/dL, respectively, p=0.000. Peak cortisol was <18 μg/dL in 7/31 NCCAH patients and in one heterozygote. Conclusions: A percentage of 21.2% NCCAH patients showed inadequate cortisol response to ACTH stimulation. In these subjects, the discontinuation of treatment on completion of growth deserves consideration.