Challenges of CYP21A2 genotyping in children with 21-hydroxylase deficiency: determination of genotype-phenotype correlation using next generation sequencing in Southeastern Anatolia.

BACKGROUND/PURPOSE: Although it is known that there is generally a good correlation between genotypes and phenotypes, the number of studies reporting discrepancies has recently increased, exclusively between milder genotypes and their phenotypes due to the complex nature of the CYP21A2 gene and methodological pitfalls. This study aimed to assess CYP21A2 genotyping in children with 21-hydroxylase deficiency (21-OHD) and establish their predictive genotype-phenotype correlation features using a large cohort in Southeastern Anatolia's ethnically diverse population. METHODS: The patients were classified into three groups: salt-wasting (SW), simple virilizing (SV) and non-classical (NC). The genotypes were categorized into six groups due to residual enzyme activity: null-A-B-C-D-E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes. RESULTS: A total of 118 unrelated children with 21-OHD were included in this study (61% SW, 24.5% SV and 14.5% NC). The pathogenic variants were found in 79.5% of 171 mutated alleles (60.2%, 22.2%, and 17.6% in SW, SV and NC, respectively). Patient distribution based on genotype groups was as follows: null-16.1%, A-41.4%, B-6.0%, C-14.4%, E-22%). In2G was the most common pathogenic variant (33.9% of all alleles) and the most common variant in the three phenotype groups (SW-38.8%, SV-22.2% and NC-23.3%). The total genotype-phenotype correlation was 81.5%. The correlations of the null and A groups were 100% and 76.1%, respectively, while it was lower in group B and poor in group C (71.4% and 23.5%, respectively). CONCLUSION: This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.

The role of placental iodine storage in the neonatal thyroid stimulating hormone surge: iodine as a driving force to adapt the terrestrial life.

PURPOSE: Iodine plays a pivotal role in adaptation during the transition from intrauterine to extrauterine life. Although it is well known that the placenta plays a role in iodine storage, a relationship between the neonatal thyroid stimulating hormone (TSH) peak and placental iodine concentration has not been established. This study focuses on the role of placental iodine concentration in the TSH surge after delivery. MATERIALS AND METHODS: This study included 42 mothers and their newborns, none of whom had perinatal risk factors. The following samples were collected to analyze iodine: placental tissue, amniotic fluid (AF), and 24-h maternal urine. Blood was drawn from the umbilical cord (uc), newborns (at the 1st-24th hours), and mothers (at 1st hour) to analyze the following hormones: TSH, freeT4/T3(fT4/fT3), human chorionic gonadotrophin (hCG), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), and cortisol. RESULTS: The mean iodine levels of placental tissue, AF, and 24-h maternal urine were as follows: 29.06 ± 45.88 µg/kg, 182.80 ± 446.51 µg/L, and 498.35 ± 708.34 µg/L, respectively. The mean TSH and hCG values were 32.41 ± 13.96mIU/ml and 30.66 ± 18.55mIU/ml, respectively, at the 1st hour. Placental iodine had strong, very strong, and weak negative correlations with TSH, hCG, and PRL, respectively (rTSH = - 0.763, p < 0.001;rHCG = - 0.919, p < 0.001; rPRL = - 0.312, p = 0.044). CONCLUSION: This study showed that the placental iodine level was inversely correlated with neonatal TSH, hCG, and PRL. It indicates that placental iodine concentration is an efficient driving force shaping the dynamic pattern of the neonatal TSH peak in addition to hCG and PRL surges, which reflects the adaptive effort in the transition from intrauterine to extrauterine life.

Coexistence of unusual and distinctive initial manifestations of severe systemic lupus erythematosus: A child's case, presenting as adrenal insufficiency associated with autoimmune polyglandular syndrome.

The involvement of multiple endocrine organs is rarely identified as initial manifestations of systemic lupus erythematosus (SLE) and autoimmune polyglandular syndrome (APS) in infancy. Childhood SLE tends to present with more severe clinical symptoms at an early age and with a set of unexpected findings. In the literature, the case reports of children presenting with SLE and APS components at the same time are extremely rare. Adrenal insufficiency may be overlooked due to mild clinical findings in later periods, except for neonates characterized by marked salt depletion and ambiguous genitalia signs. Moreover, adrenal insufficiency as an initial symptom in childhood is quite unusual as a component of SLE-associated APS. This report describes the overlap of unexpected, unusual, and severe clinical findings in an infant with APS with a comorbidity of SLE, where the involvement of multiple endocrine organs coexists with multiple serious clinical manifestations from the beginning.

Changes in thyroid volume and insulin-like growth factor 1 in pre- and post-pubertal obese children.

BACKGROUND: There is a mutual dynamic interaction between thyroid volume (TV), insulin-like growth factor-1 (IGF-1), and body mass index (BMI). These covariates undergo a change with the transition into puberty. The heterogeneity of the variates and study populations complicate the evaluation of the role of pure pubertal effect. OBJECTIVE: The purpose of this study was to investigate the effect of puberty on IGF-1 and TV in a predetermined homogenous population such as obese children. SUBJECTS AND METHODS: Three hundred and eighty children (202 girls and 178 boys) aged between 6 and 18 were enrolled in this prospective study. The children were assigned to two groups according to their pubertal status, i.e., prepubertal (n = 169) and postpubertal (n = 211). According to age and sex, the obese group (n = 222) was made up of children at and above the 95th percentile, and the control group (n = 158) of children under the 85th percentile. The following parameters were evaluated in all children: BMI, pubertal status, TV, and serum IGF-1, IGFBP-3, and IGF-1:IGFBP-3 molar ratio. RESULTS: In comparison to the prepubertal obese group, the obese group at Tanner stage 2 had a larger mean TV (P = 0.008) and higher IGF-1 level (P = 0.033). There was a positive correlation between IGF-1 and TV both in the prepubertal and pubertal group (r169= 0.369, P = 0.001; r211= 0.316, P = 0.004, respectively), whereas there was no correlation between IGF-1 and BMI (r169= 0.99, P = 0.092; r211= 0.094, P = 0.088, respectively). CONCLUSION: This study showed that the TV and serum IGF-1 levels were increased in obese children in the early stage of puberty and that there was a positive correlation between these two variables in all children, which shows the specific effect of the early stage of puberty on the increase in TV and IGF-1 levels and suggests that increased TV is associated with the increase in IGF-1 levels in a homogenous group such as obese children.

Open versus laparoscopic donor nephrectomy in live related renal transplantation.

BACKGROUND: This analysis sought to evaluate the efficiency and safety of laparoscopic nephrectomy (LDN) for the donor, the recipient, and the graft. LDN seems to have advantages over the open donor nephrectomy (ODN) in length of hospital stay, postoperative comfort, and pain control. METHODS: The results of 40 patients who underwent LDN between October 2000 and September 2003 were compared to those of 40 ODN patients just preceding the LDN patients. Eight laparoscopy patients required conversion to an open procedure due to bleeding (4; two major and two minor), technical problems with the instrument (n = 1) and difficulty in the dissection (n = 3). RESULTS: The demographic data, percentages of right and left nephrectomy, number of vessels, rates of acute rejection episodes, as well as the rates of urologic and vascular complications were similar between the two groups. The time of hospital stay was shorter, and the duration of the operation and of the warm ischemia time were significantly longer for the LDN group. The postoperative decline in serum creatinine levels were similar for the two groups. Graft survival rates were 91.7% at both the first and third years in the LDN group; 92.5% and 87.0% for the ODN group, a difference that was not statistically significant. CONCLUSION: LDN is as efficient and safe as ODN for donors, recipients, and grafts.

Exchange kidney transplantation: a good solution in living kidney transplantation.

OBJECTIVES: Kidney transplantation seems to be the best treatment modality for end-stage renal disease patients. But not every patient on the waiting list is able to find a kidney. To increase transplantations, centers have tried to find new options. MATERIAL AND METHODS: In the period of November 1994 through June 2004, among 265 renal transplantations, 182 (68.6%) were from living related donors, namely first- and second-degree relatives, spouses, or parents-in-law of the patients. Four patients, who did not have living related donors, had the opportunity of renal transplantation from living donors by exchanging their donors. RESULTS: All the kidneys functioned immediately. No complications and no acute rejection episodes were observed in the postoperative period up to 12 months. Serum creatinine levels were 1.9, 1.2, 1.6, and 2.4 mg/dL on postoperative day 7; 1.4, 1.0, 1.1, and 1.1 mg/dL at 1 month after transplantation; 1.5 and 1.2 mg/dL at month 6 after transplantation; 1.6 and 1.4 mg/dL at 1 year after transplantation. CONCLUSION: We believe that exchange kidney transplantations represent a good alternative for end-stage renal patients who do not have suitable close living related donors.