ANALYSIS OF THE VITAMIN D RECEPTOR BSMI GENE POLYMORPHISM IN CHILDREN WITH GROWTH HORMONE DEFICIENCY.

OBJECTIVE: The aim: The objective of the study was to investigate the polymorphism of the vitamin D receptor (VDR) BsmI gene in children with growth hormone deficiency and the level of their vitamin D supply. PATIENTS AND METHODS: Materials and methods: Sixteen children diagnosed with of growth hormone deficiency who were treated at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine¼ were examined. The patient's gender and age, the anthropometric data, the vitamin D level in the blood, the bone age, the GH level, the IGF-1 levels, the level of calcium in the blood and VDR gene polymorphism were taken into account. RESULTS: Results: It was shown that in the presence of the G/A genotype, the risk of growth hormone deficiency development was increased OR = 1,096 (95% CI 0.39-3.02; p = 0.86). For BsmI, mean values of height, body mass, height SDS, serum 25(OH)D, in the studied population (16 children) were 123.49 ± 19.62 cm, 26.96 ± 11.11 kg, -2.25 ± 0.85, 48.86 ± 16.71 nmol/l, respectively; total calcium level consisted of 2.40 ± 0.12 mmol/l, serum phosphorus - 1.43 ± 0.11 mmol/l. CONCLUSION: Conclusions: The allele frequency of the VDR BsmI polymorphism was 62.5% for the G allele (n = 20) and 37.5% for the allele A (n = 12). The G allele carrier of the polymorphic locus BsmI rs1544410 of the VDR gene (rs11568820) is associated with an increased risk of growth hormone deficiency development OR = 1.31 (95% CI 0.62-2.75; p = 0.47).

Thyroid Cancer and Benign Nodules After Exposure In Utero to Fallout From Chernobyl.

Background: Children and adolescents exposed to radioactive iodine-131 (I-131) in fallout from the 1986 Chernobyl nuclear accident appear to be at increased risk of thyroid cancer and benign thyroid nodules. The prenatal period is also considered radiosensitive, and the fetal thyroid can absorb I-131 from the maternal circulation. Objectives: We aimed to estimate the risk of malignant and benign thyroid nodules in individuals exposed prenatally. Methods: We studied a cohort of 2582 subjects in Ukraine with estimates of I-131 prenatal thyroid dose (mean = 72.6 mGy), who underwent two standardized thyroid screening examinations. To evaluate the dose-response relationship, we estimated the excess OR (EOR) using logistic regression. Results: Based on a combined total of eight cases diagnosed at screenings from 2003 to 2006 and 2012 to 2015, we found a markedly elevated, albeit not statistically significant, dose-related risk of thyroid cancer (EOR/Gy = 3.91, 95% CI: -1.49, 65.66). At cycle 2 (n = 1,786), there was a strong and significant association between I-131 thyroid dose and screen-detected large benign nodules (≥10 mm) (EOR/Gy = 4.19, 95% CI: 0.68, 11.62; P = 0.009), but no significant increase in risk for small nodules (<10 mm) (EOR/Gy = 0.34, 95% CI: -0.67, 2.24; P = 0.604). Conclusions: The dose effect by nodule size, with I-131 risk for large but not small nodules, is similar to that among exposed children and adolescents in Belarus. Based on a small number of cases, there is also a suggestive effect of I-131 dose on thyroid cancer risk.

In utero exposure to iodine-131 from Chernobyl fallout and anthropometric characteristics in adolescence.

Prenatal exposure to external radiation has been linked to growth retardation among atomic bomb survivors in adolescence. It is unclear from previous studies whether in utero exposure to internal radiation such as iodine-131 (I-131), which concentrates in the thyroid gland, has an effect on physical growth. We examined the associations between estimated thyroid gland dose from prenatal exposure to I-131 and self-reported height and weight in a cohort of 2,460 individuals exposed to radioactive fallout from the 1986 Chernobyl nuclear accident [mean I-131 dose = 72 (mGy)] and screened for thyroid diseases in adolescence. Using multivariable linear regression models, we estimated the mean differences in height, weight and body mass index (BMI) per unit increase in dose (100 mGy) in models adjusted for gender, age at examination, type of residence (rural/urban) and presence of thyroid disease diagnosed at screening. All of the adjustment factors as well as the trimester of exposure were evaluated as potential modifiers of the dose response. Overall, no significant dose response was found for height (P = 0.29), weight (P = 0.14) or BMI (P = 0.16). We found significant modification of the dose response for weight and BMI by presence/absence of thyroid disease (P = 0.02 and P = 0.03, respectively), but not for other factors. In individuals without thyroid disease (n = 1,856), there was a weak, significant association between I-131 thyroid dose and higher weight (210 g per 100 mGy, P = 0.02) or BMI (70 g/m² per 100 mGy, P = 0.02) that depended on individuals (n = 52) exposed to ≥500 mGy. In individuals with thyroid disease (n = 579, 67.4% with simple diffuse goiter) no significant association with I-131 for weight (P = 0.14) or BMI (P = 0.14) was found. These results do not support the hypothesis that in utero exposure to I-131 at levels experienced by a majority of study subjects may be associated with meaningful differences in adolescent anthropometry. However, additional studies are needed to clarify whether in utero exposure to I-131 at levels > = 500 mGy may be associated with increases in weight/BMI and to evaluate the confounding or modifying role of thyroid disease, past iodine deficiency, maternal and prenatal/postnatal factors.

24-month use of once-weekly GH, LB03002, in prepubertal children with GH deficiency.

BACKGROUND: Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients. OBJECTIVE: The aim of the study was to examine efficacy and safety of LB03002, a sustained-release GH formulation for once-weekly administration. DESIGN: We conducted a phase III, 12-month, multinational, randomized, open-label, comparator-controlled trial with a 12-month uncontrolled extension. PATIENTS: Prepubertal GH treatment-naive GH-deficient children (mean age, 7.8 y) participated in the study. INTERVENTION: We administered once-weekly LB03002 (n=91) or daily GH (n=87) for 1 year, followed by once-weekly LB03002 for all patients for another year (LB03002 throughout, n=87; switched to LB03002, n=80). OUTCOME MEASURES: Height, height velocity (HV), IGF-1, GH antibodies, and adverse events were determined throughout. Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance. RESULTS: Mean±SD HV during year 1 was 11.63±2.60 cm/y with LB03002, and 11.97±3.09 cm/y with daily GH, with increases from baseline of 8.94±2.91 and 9.04±3.19 cm/y, respectively. The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y (99% confidence interval, -1.45 to 0.60 cm/y). Mean HV also remained above baseline in year 2 (8.33±1.92 cm/y in the LB03002 throughout group, and 7.28±2.34 cm/y in the switched to LB03002 group). Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in >90% of cases. CONCLUSIONS: Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.