Journal of Clinical Research in Pediatric Endocrinology最新文献

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 (LMIC) like 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.

Objectives: This study aims to evaluate the off-label use of the MiniMed™ 780G system in children under seven years old, as clinical outcomes in this age group are less established despite the improvements in glycemic control seen with MiniMed™ 780G therapy.

Methods: Children under seven years old with type 1 diabetes (T1D) using MiniMed™ 780G pump therapy were retrospectively compared with children of similar age and gender using MiniMed™ 640G insulin pump therapy and multiple-dose insulin (MDI) therapy with continuous glucose monitoring systems (CGMs). CGM metrics, total daily insulin dose (TDI), and HbA1c levels were evaluated retrospectively at baseline and at the 3rd, 6th, and 12th months.

Results: At the initiation of MiniMed™ 780G therapy, the mean age was 5,25±1,22 years (range: 2,8-6,8 years), and the mean TDI was 10,12±4,34 U/day (range: 4,5-17 U/day). The glucose management indicator (GMI) and HbA1c remained lower in the MiniMed™ 780G group at the 3rd, 6th, and 12th months compared to baseline (p=0,009 and p<0,001, respectively). In the MiniMed™ 780G group, Time Above Range (TAR) was significantly lower at the 3rd, 6th, and 12th months (p=0,018, 0,017, and 0,04, respectively), and Time in Range (TIR) was higher at the 3rd and 12th months (p=0,026 and 0,019, respectively). The coefficient of variation (CV) and HbA1c were lower at the 12th month (p=0,008 and 0,015, respectively) compared to the other groups. No instances of ketoacidosis or severe hypoglycemic events were observed in any of the children during the follow-up period.

Conclusions: The absence of significantly higher levels of hypoglycemia compared to other groups at any time point, along with a significant decrease in TAR across all time points, a significant increase in TIR at the 3rd and 12th months, and a significant decrease in HbA1c and CV, indicates that the MiniMed™ 780G system is both safe and effective for children under seven years old.

Background and aim: Children with type 1 diabetes mellitus are susceptible to arrhythmias and sudden cardiac death. In this study, we aimed to explore the arrhythmia risk among children with type 1 diabetes mellitus by assessing electrocardiographic parameters.

Methods: A total of 165 children diagnosed with type 1 diabetes mellitus, aged 10-18 years, and 154 healthy children matched for age and gender without any chronic diseases, were included in the study. The electrocardiographical ventricular depolarization-repolarization parameters of both groups and the correlation of these parameters with length of time since diagnosis of type 1 diabetes mellitus, metabolic control, and the presence of additional complications were evaluated.

Results: The groups were similar in terms of age, gender, weight, height, and BMI (p>0.05). The median length of time since diagnosis of diabetes was 5 years. QT (maximum), QTc (minimum and maximum), QT and QTc dispersion, Tp-e (minimum and maximum), Tp-e dispersion, Tp-e/ QTc-max values were significantly higher in the diabetic group compared with controls although QTc intervals are within normal ranges. No statistically significant correlation was observed between electrocardiographic findings and length of time since diagnosis of type 1 diabetes mellitus, HbA1c levels, or complications.

Conclusion: As children with type 1 diabetes mellitus are at high risk of impaired ventricular depolarization and repolarization, they should undergo cardiac assessment and regular electrocardiographic monitoring.

Objective: The study aims to determine the normal values of thyroid volume and tracheal index in healthy term newborns born in an iodine-sufficient population. Additionally, we investigated the usability of a handheld device for assessing the tracheal index.

Methods: Thyroid imaging was performed at 0-2 days and 15-30 days using handheld and portable ultrasound devices. Thyroid volume and tracheal index were calculated using standard formulas.

Results: A total of 144 healthy term newborns with a mean birth weight 3230 g were enrolled. The normal thyroid volume for the entire population was 0.66 ± 0.25 ml at 0-2 days, which significantly increased to 1.12 ± 0.33 ml at 15-30 days (p<0.01). There were no significant differences in thyroid volume between genders in either age group (p=0.246 and p=0.879). Thyroid volume correlated with birth weight, length, and head circumference, with the strongest correlation being with birth weight (r=0.404, p<0.001; r=0.252, p=0.002; r=0.223, p=0.007, respectively). The tracheal index at 0-2 days was 1.84±0.30 in girls, 1.82±0.27 in boys, and 1.83±0.29 overall. At 15-30 days, it was 1.99±0.23 in girls, 2.00±0.28 in boys, and 1.99±0.25 overall. Similar to thyroid volume, the tracheal index increased with age (p<0.01), with no significant gender differences in either age group (p=0.593 and p=0.886). Thyroid volume and tracheal index were moderately correlated in both measurements (rho=0.538, p<0.01). Measurements of the trachea, and thyroid lobe widths using portable and handheld ultrasound devices were correlated (r=0.449, p<0.01; r=0.638, p<0.01; r=0.497, p<0.01). There was also a correlation between tracheal index measurements using both devices in both the first and second measurements.

Conclusion: This study provides normative data on thyroid volumes and tracheal index in newborns from an iodine-sufficient population. The tracheal index can estimate thyroid size when volume calculation is not feasible and handheld ultrasound devices are effective for this assessment.

Objective: To assess gonadal function in adolescent male patients with β-thalassemia who underwent successful hematopoietic stem cell transplantation (HSCT) during childhood or adolescence.

Methods: Fifty-two male patients with β-thalassemia, aged ≥10 years, who had undergone HSCT ≥2 years were included. Clinical data, such as age, genital Tanner (GT) stage at HSCT and enrollment, serum ferritin levels, and cumulative doses of alkylating agents, were collected. Gonadal function was evaluated through measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B levels, and semen analysis.

Results: Age at enrollment and HSCT were 17 (10-31) and 9 (1-19) years, respectively. The duration from HSCT to enrollment was 7.5 (2-20) years. Of 52 patients, 46 (88%) exhibited Sertoli cell dysfunction. Thirty-one patients had relatively small testes for their GT stage, 34 of 44 with GT V had elevated FSH of ≥5 IU/L, and 20 of 49 with GT stages II-V had low serum inhibin B levels. None of the patients with GT stage V showed Leydig cell dysfunction or gonadotropin deficiency. Serum FSH ≥8 IU/L showed the best diagnostic accuracy for detecting oligo- and azoospermia. All 39 patients who underwent semen analysis had >1 abnormal parameters. Having relatively small testes for GT stage and serum FSH ≥8 IU/L were associated with oligo- and azoospermia (p <0.01).

Conclusions: Male patients with β-thalassemia after HSCT experienced universal spermatogenesis impairment and frequent Sertoli cell dysfunction but their Leydig cell function appears to be preserved. The high likelihood of future subfertility should be informed before HSCT.

Turner syndrome (TS) is the most common sex chromosome abnormality among females, characterised by short stature, hypergonadotropic hypogonadism, congenital heart anomalies, and an increased risk of autoimmune diseases. Although TS does not typically increase the absolute risk of malignancy, specific cancers, such as those affecting the nervous system and gastrointestinal tract and malignant melanoma, may occur more frequently. Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma, typically affecting adults but also seen in children and adolescents. We report an 11.2-year-old girl with TS presenting with substantial weight gain and short stature. Clinical examination revealed characteristic TS features and karyotype analysis confirmed mosaic TS. Following growth hormone (GH) therapy, the patient developed persistent, erythematous, itchy skin lesions diagnosed as CD4+ MF. GH therapy was discontinued, and topical steroids controlled the skin lesions effectively. MF in TS is rare and unexpected, especially in a child. The coexistence of these conditions suggests a potential link between TS and an increased risk of MF, possibly due to T-cell dysregulation or autoimmune processes. While the clinical course of MF is typically indolent, careful monitoring and annual dermatologic evaluations are recommended for TS patients, particularly when skin lesions are present. This is the first reported case of MF in a child with TS. This case emphasises the importance of carefully evaluating skin lesions in patients with TS and suggests considering MF as a differential diagnosis.

Noonan Syndrome (NS) diagnosis is challenging due to diverse clinical manifestations. Here, our case report highlights MAP3K7's novel role in NS. A 10.4-year-old female patient presented with short stature and suggestive clinical findings of RASopathy. Despite atypical facial features, the patient met two major diagnostic criteria of Van der Burgt.Initial genetic testing for known NS-associated genes did not find any variants. Later, whole exome sequencing (WES) discovered a unique de novo heterozygous variant (c.65C>A, p.(P22H)) in the MAP3K7. This variant, categorized as a variant of uncertain significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, raised questions about its potential role in NS. The patient's clinical presentation deviated from classical manifestations of MAP3K7-associated syndromes, underscoring the genetic and molecular mechanisms' complexity. Notably, this is the first case reported to associate MAP3K7 variants with NS, advancing knowledge of the condition's genetic causes. Despite challenges in NS diagnosis, proper management, including recombinant growth hormone therapy, is crucial for optimizing growth potential. The case underscores MAP3K7 as a potential candidate gene for NS, and more functional genetic investigations are required to clarify the delicate interaction between genetic abnormalities, the RAS/MAPK pathway, and clinical manifestations observed in NS cases.

Gonadoblastoma is a rare ovarian tumor composed of sex cord cells and primitive germ cells. While the majority of gonadoblastomas are found in individuals with 46,XY gonadal dysgenesis, they are also rarely seen in patients with a 46,XX karyotype. We report a case of a fourteen-year-and-six-month-old girl presenting with an uncommon cause of virilization due to a virilizing ovarian tumor. The patient underwent bilateral salpingo-oophorectomy. Upon histopathological examination, the excised tumor was confirmed to be bilateral gonadoblastoma, with dysgerminoma on the left side. Malignant gonadal tumors should be considered in cases of primary gonadal insufficiency with a 46,XX karyotype and progressive virilization. Even when laboratory and imaging tests show no abnormalities, a gonadal biopsy should be considered.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.