Journal of Clinical Research in Pediatric Endocrinology最新文献

Osteogenesis imperfecta (OI) is a genetically and phenotypically heterogeneous group of disorders primarily characterized by bone fragility, impaired growth, and skeletal deformities. Although OI was historically attributed to monoallelic pathogenic variants in COL1A1 and COL1A2, recent advances have identified autosomal recessive forms caused by defects in genes involved in collagen biosynthesis and processing. SERPINH1 encodes heat shock protein 47 (HSP47), a collagen-specific molecular chaperone essential for proper folding of the procollagen triple helix and its transport to the Golgi apparatus. Loss-of-function variants in SERPINH1 cause OI type X, a rare autosomal recessive form associated with moderate to severe bone fragility. We evaluated two Turkish siblings with clinical features of OI, including short stature, recurrent fractures, low bone mineral density, and skeletal deformities. Exome sequencing identified a novel homozygous missense variant in SERPINH1 (NM_001235.5: c.250G>C; p.G84R) in both siblings. Despite sharing the same genotype, they exhibited marked intrafamilial phenotypic variability: the 8-year-old brother presented with early-onset, severe skeletal manifestations, whereas his 11-year-old sister showed a milder, later-onset phenotype. This report expands the genotypic and phenotypic spectrum of SERPINH1-related OI, highlights intrafamilial variability, and adds further data on Turkish patients with this rare condition.

Objective: To examine the implementation of a new psychiatric follow-up model for patients with differences of sexual development (DSD), a group of conditions affecting gender determination and differentiation, focusing on the model’s impact on patient care and residents’ training.

Methods: Data from patients monitored between March 2000 and November 2023 and 28 child and adolescent psychiatry residents in a tertiary-care center were analyzed. Data was collected before and after implementing the new model using psychiatric assessment and the Clinical Global Impression (CGI) and Global Assessment Scale (GAS).

Results: The patient cohort consisted of 129 patients with DSD, of whom 10 (7.75%) were lost to follow up. Of the remaining 119 patients, 89 (74.8%) were monitored by two expert specialists prior to the model’s implementation, while 30 (25.2%) were cared for by junior child and adolescent psychiatry residents under supervision following the implementation of the new model. The mean age of the patients was 10.86±6.32 years. No significant differences in the prevalence of psychiatric disorders or in CGI or GAS scores before and after implementing the new education model were found (p>0.05). The most common psychiatric diagnosis in our sample was attention-deficit/hyperactivity disorder (19.4%), followed by intellectual disability and major depressive disorder, each accounting for 14.0%. Residents reported enhanced competence in managing patients with DSD (14.3%), improved communication skills, and better identification of subthreshold psychiatric symptoms (25%), as well as a greater understanding of the multidisciplinary approach (14.3%).

Conclusion: This study highlighted the importance of structured psychiatric support in the management of DSD. Furthermore, the education of future psychiatrists was subjectively improved.

Objective: Predicting whether children with pre-pubertal short stature will achieve catch-up growth to a normal height or remain short remains a clinical challenge. As body composition plays a vital role in growth, we aimed to compare longitudinal body composition changes in children with short stature who either achieved normal height by the onset of the growth spurt or remained short.

Methods: This longitudinal, retrospective, cross-sectional, cohort study analyzed anthropometric and body composition data of children aged 8 and 12 years, allowing for both longitudinal tracking and cross-sectional comparisons. Participants were categorized into three groups: short-to-short statured (short stature at 8 and 12 years, n=177), short-to-normal statured (short stature at age 8 and normal stature at 12, n=90), and control (normal stature at both ages, n=7,195). Height, weight, body fat mass (BFM), skeletal muscle mass (SMM), body mass index (BMI), BFM index (BFMI), and SMM index (SMMI) were assessed. Growth variations were examined using a difference-in-difference estimator.

Results: Cross-sectional analysis showed the short-to-short group had significantly lower weight, BFM, SMM, BMI, BFMI, and SMMI compared to controls at both ages. Longitudinally, the short-to-normal group exhibited significantly greater increases in height [0.87 and 0.95 standard deviation scores (SDS) for boys and girls, respectively], weight (0.59 and 0.68 SDS), and SMMI (0.75 and 0.50 SDS) compared to the short-to-short group. However, BFMI increases were not significant.

Conclusion: Children with pre-pubertal short stature who achieved a normal height showed the most significant increase in SMMI. Children with lower increases in SMMI may require further assessment for continued short stature.

Objective: In cases of precocious puberty, the determination of bone age (BA) is usually performed by clinicians using the Greulich-Pyle (GP) atlas, and there can be significant variation between assessors. The aim of this study was to compare predicted adult height (PAH) calculations based on BA read by the automated BA method “BoneXpert” (BX) with clinician-determined BA-based PAH calculations.

Methods: Girls who presented with suspicion of precocious puberty and normal pubertal variants, such as premature thelarche and premature adrenarche, and whose BA determined by both BX and two different clinicians were followed up until reaching near-final height (NFH). Those whose breast development started before the age of 8 years were considered as precocious puberty. Four PAH calculations were performed with two different estimated height calculation methods, the Bayley-Pinneau (BP) and Roche-Wainer-Thissen based on two different BA predictions (Clinician-GP and BX-GP). PAH-standard deviation score (PAH-SDS) and NFH-SDS values of the patients were compared.

Results: The median chronological age of the 44 girls included at presentation was 9.3 years, while the median BA was 10.4 years and 10.6 years according to clinician-GP and BX-GP, respectively; mean height-SDS was 0.75 and target height-SDS was -0.28. When they reached NFH, the height-SDS was -0.02. Final analyzes were performed in 26 cases who did not have low birth weight and did not receive puberty-arresting treatment. Delta PAH-SDS-NFH-SDS (Δ-SDS) was compared according to the four different PAH calculations. The closest PAH-SDS value measurement to NFH-SDS was calculated by BP based on BA determined by the BX-GP method (-0.09).

Conclusion: PAH calculations using the BP method based on BX-derived GP readings most accurately predict NFH in girls with precocious puberty, and normal pubertal variants.

Objective: This study was conducted to assess the perspectives of pediatric endocrinologists in Türkiye about the management of congenital hypothyroidism (CH) and to analyze the potential impact of work environment and professional experience on different attitudes.

Methods: The members of the Turkish Society for Pediatric Endocrinology and Diabetes were invited to participate in an online survey. An evaluation was made after obtaining survey responses from 95 (19%) of 502 members.

Results: Participants’ mean age was 42.0±9.6 years, 46.3% of them were working in a university hospital, and 48.6% had >7 years of work experience. When the participants were asked about their approach to a 1-3-week-old neonate whose serum thyroid stimulating hormone (TSH) concentration was 6-20 mU/L with a serum-free thyroxine (FT4) concentration within the age-specific reference interval, 97.7% of the participants preferred to monitor without medication. Only 24% of physicians consider starting treatment immediately if the serum TSH concentration is 20-40 mU/L with a normal FT4 level. While 5.3% of participants preferred dual imaging (ultrasound and scintigraphy), 90.5% requested only thyroid ultrasound for etiological investigation. When considering the discontinuation of levothyroxine (LT4) in patients with a normal thyroid gland and a low LT4 dose, 28.4% of the participants stated that treatment should be stopped at the earliest at the age of 3 years, 16.8% at 2 years, 5.3% at 1 year, 16.8% at 6 months, and 32.6% at any time if the TSH levels remain low despite the low dosage. Physicians with over 7 years of experience may discontinue medication if TSH is low, even with a lower dose, more frequently than those with less experience (p=0.011). There were no significant differences in the approach of the physicians between employees at university hospitals and other health institutions.

Conclusion: Although the attitudes of pediatric endocrinologists working in Türkiye towards the management of CH are generally consistent with the recommendations of international guidelines, their approaches to the treatment for isolated neonatal TSH elevation, thyroid imaging preferences and time to discontinue treatment differ significantly. These different attitudes, which are similar between all subgroups by experience and work setting, reflect the differences in local conditions in Türkiye and underline the need for a national consensus on the management of CH.

Objective: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterised by early-onset diabetes and inherited in an autosomal dominant manner. MODY results from heterozygous mutations in genes important for pancreatic β-cell development or function. The objective was to identify the most common and rarest types of MODY amongst our cases with genetically confirmed MODY diagnosis, to evaluate clinical and laboratory features and treatment regimens.

Methods: The epidemiological, auxological, and laboratory data, genetic analysis results and treatment regimens of patients diagnosed with MODY were retrospectively evaluated.

Results: Of the 44 cases included, 27 (61.4%) were male and the median age at diagnosis was 10.07 (1-16.8) years. There was a family history of diabetes in 42 (95.5%) cases. The distribution of gene variants was: 25 (55.8%) glucokinase (GCK), 4 (9.1%) hepatocyte nuclear factor-4-alpha, 4 (9.1%) carboxyl ester lipase, 2 (4.5%) B lymphocyte kinase, 4 (9.1%) ATP-binding cassette subfamily C member 8, 2 (4.5%) Kruppel-like factor 11, 1 (2.3%) insulin (INS), 1 (2.3%) potassium channel, inwardly rectifying, subfamily J member 11, and 1 (2.3%) adaptor protein, phosphotyrosine interaction, pH domain, and leucine zipper containing 1. At presentation, 23 (52.3%) of the cases had incidental hyperglycemia while 14 (31.8%) had polyuria and polydipsia. Diabetic ketoacidosis was detected in 4 (9.1%) and ketonemia in 3 (6.9%). At least one of the diabetes autoantibodies (anti-glutamate acid decarboxylase, anti-islet cell antibodies, anti-insulin autoantibodies) was detected in 11 (25%) cases, of which 7/11 were islet antibodies, and 5 patients (11%) had two autoantibodies positive simultaneously. In terms of treatment, 26 (59%) received diet and lifestyle changes only, 18 (41%) received oral antidiabetic agents and/or insulin, and 6 (13.6%) received both oral antidiabetic agents and insulin.

Conclusion: The most common type of MODY in our cohort was GCK-MODY. Although MODY is generally known as an autoantibodynegative type of diabetes, autoantibody positivity was detected in 11 of 44 cases (25%) in the present study.

Type 1 diabetes mellitus (T1DM) is a chronic condition requiring lifelong management that affects a large number of children and adolescents globally. While diabetes care has improved over the years, low-middle income countries, such as Indonesia, still struggle to achieve optimal diabetes care due to limited access to healthcare professionals, insulin, diabetes technologies, and self-monitoring blood glucose (SMBG) devices. Data from the Indonesian Pediatric Society registry has reflected a stark increase in the number of children with T1DM, with the current prevalence significantly concentrated on Java island and a noticeable underreporting in rural regions. Another major challenge is the uneven distribution of pediatric endocrinologists, resulting in a low specialist-to-patient ratio. This imbalance, coupled with inadequate access to comprehensive diabetes care, complicates effective T1DM management. While the national insurance covers a portion of costs associated with T1DM care, vital aspects of T1DM management including SMBG devices are still not covered, resulting in significant financial burden to families. Access to diabetes technologies that improve glycemic control and quality of life of patients is also still largely limited. This paper evaluates the current state and future needs for insulin and SMBG in Indonesia, emphasizing the necessity of strategic interventions to improve access and quality of diabetes care.

Objective: Neonatal screening for congenital adrenal hyperplasia (CAH) was implemented nationwide in Türkiye in 2022. The performance of this screening program in its first year was assessed.

Methods: This retrospective, descriptive study included neonates born in Türkiye between January 1 and December 31, 2022, with gestational age ≥32 weeks and birth weight ≥1500 grams. The screening protocol used a two-tier approach. In the first step, 17α-hydroxyprogesterone (17-OHP) levels were measured using fluoroimmunoassay (FIA) in dried blood spots (DBS) collected at 3-5 days of life. Infants with positive results underwent second-tier testing using liquid chromatography-tandem mass spectrometry to measure 17-OHP, 21-deoxycortisol (21-DF), cortisol (F), and 11-deoxycortisol (S) in DBS. Those with a steroid ratio (21-DF+17-OHP)/F ≥1 were referred to pediatric endocrinology clinics for diagnostic evaluation.

Results: Of 1,096,069 neonates screened (including 149,652 refugees), second-tier tests were performed on 70,455 (6.88%) infants, and 3,429 (0.27%) were referred to clinics, resulting in 91 confirmed cases of classical 21-hydroxylase deficiency (21-OHD) CAH (77; salt-wasting, 14; simple virilizing). Twenty-two patients were diagnosed with non-classical 21-OHD CAH. The frequency of classical 21-OHD was 1 in 12,044. The first-tier FIA-17-OHP values were below 17.5 ng/mL in 99.8% of healthy neonates with ≥36 weeks gestation or ≥2500 grams and below 50 ng/mL in those with 32-36 weeks or 1500-2500 grams.

Conclusion: Neonatal CAH screening facilitates early diagnosis of 21-OHD and improved patient care. Using refined cut-offs may reduce referrals six-fold and eliminate second-tier testing for 95% of infants. Ongoing evaluation can enhance the efficiency and cost-effectiveness of the screening protocol.

Objective: Predicted adult height (PAH) can be calculated using methods such as Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and BoneXpert based on bone age (BA) assessment. Since these methods were developed for healthy children, varying results have been reported regarding their efficacy across different patient groups. Our aim was to determine the most accurate method for PAH by comparing the BP, RWT, and BoneXpert methods in boys with constitutional delay of growth and puberty (CDGP).

Methods: Male patients with CDGP who had reached their final height (FH) were included in the study. Two experienced clinicians reassessed left-hand and wrist radiographs taken at the time of diagnosis using the Greulich-Pyle (GP) atlas to manually determine BA. Among the methods used for PAH, the GP atlas was used for BP and RWT, while we used the intrinsic GP-based application with BoneXpert.

Results: For the 62 boys included, the mean age at diagnosis was 14.2±0.8 years, with 58.1% (n=36) having a similar family history. The mean height standard deviation (SD) score was -2.1±0.9, and 24.2% (n=15) of patients received low-dose testosterone induction therapy. The median (range) BAs were 12.5 (11.5-13.0) years using the GP atlas and 12.6 (11.8-13.4) years with BoneXpert (p<0.001). Boys who were or were not treated with testosterone therapy had similar mean height SD scores, median testicular volumes, and median BAs assessed by both methods. The mean target height and FH SD scores were -0.6±0.6 and -0.6±0.9, respectively (p=0.8). Almost all patients (n=60, 97%) achieved adult height within the target range, with no significant difference in the FH SD score between boys who received testosterone and those who did not (p=0.1). There was no significant difference between the FH and PAH when estimated by the BP and RWT methods (p=0.2 and p=0.6, respectively), while the BoneXpert method underestimated the FH (p<0.001). The BP and RWT methods provided better predictions in patients with BA ≤2 years compared to BoneXpert (p=0.3 and p=0.4 vs. p<0.001, respectively). Conversely, RWT and BoneXpert methods were more accurate in PAH in boys with delayed BA >2 years (p=0.1 and p=0.1, respectively), while the BP method resulted in overestimation (p=0.003).

Conclusion: The RWT method was found to be a better predictor of FH compared to the BP or BoneXpert methods in boys with delayed BA ≤2 years and >2 years.

Objective: Although neonatal screening programs have reduced severe intellectual disability, children with congenital hypothyroidism (CH) are still at risk for neurodevelopmental deficits and a lower quality of life (QoL). The aim of this study was to evaluate cognitive profiles, prevalence of neurodevelopmental disorders, and QoL in children with CH.

Methods: A longitudinal study was conducted at the northern reference endocrinology unit for CH in Portugal. Cognitive assessments were performed at four time points using standardized intelligence scales. Diagnoses of attention deficit hyperactivity disorder (ADHD), learning disorders, and intellectual disability were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-DSM-V criteria. QoL was measured using the Pediatric Quality of Life Inventory-PedsQL™.

Results: Forty-six children (mean age 9.1 years, 58.7% female) were included. While overall intelligence quotients (IQ) scores were normal, later treatment was associated with significantly lower performance IQ (r=-0.50, p=0.028) and perceptual organization index (r=-0.57, p=0.022). ADHD was present in 26%, and affected children showed lower verbal IQ (90.2 vs. 106.8, p=0.022), perceptual organization index (79.9 vs. 95.2, p=0.041), and school-related QoL (63.3 vs. 81.6, p=0.002). QoL scores were comparable to the Portuguese pediatric population, but treatment delays were linked to lower total QoL (r=-0.45, p=0.002), particularly in emotional and social domains.

Conclusion: Early thyroid hormone therapy is essential to mitigate neurocognitive deficits and improve QoL in CH. While severe intellectual disabilities are rare, non-verbal deficits persist, emphasizing the need for timely treatment and continuous monitoring.