Annals of Pediatric Endocrinology & Metabolism最新文献

Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients.

Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing.

Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%).

Conclusion: Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Purpose: Few data on the clinical course after levothyroxine (L-T4) discontinuation in pediatric patients with Hashimoto thyroiditis (HT) are available. We investigated outcomes and predictors for successful withdrawal from L-T4 among children with HT.

Methods: Among 168 patients diagnosed with HT between January 2000 and March 2021 at Seoul National University Children's Hospital and in whom L-T4 therapy was initiated during childhood, we attempted to discontinue this therapy in 47, 3 boys and 44 girls. L-T4 was restarted when patients developed overt or subclinical hypothyroidism (thyroid-stimulating hormone [TSH] levels≥10 mIU/L) after L-T4 discontinuation.

Results: Median age at discontinuation was 15.4 years (12.7-18.4 years) with a median duration of L-T4 therapy of 47 months (20.3-80.3 months). During the median 30 months of follow-up (10.6-61.0 months) after L-T4 discontinuation, 33 (70.2%) developed thyroid dysfunction. Among these patients, 17 were eventually restarted on L-T4. TSH levels over 50 mIU/L at L-T4 initiation (hazard ratio, HR 3.5, P=0.002), age under 12 years at L-T4 discontinuation (HR 11.1, P=0.0001), and TSH levels higher than the upper 50% of normal (above 2.25 mIU/L in the present study) at L-T4 discontinuation (HR 2.7, P=0.014) were significantly predictive for overt hypothyroidism or subclinical hypothyroidism after L-T4 discontinuation. In addition, age under 12 years at L-T4 discontinuation was only predictive factor for restarting L-T4 medication (HR 4.3, P=0.012).

Conclusion: L-T4 discontinuation in pediatric patients with HT resulted in thyroid dysfunction in 70.2% of cases; 36.2% of patients who attempted discontinuation required resumption of L-T4. Older age and lower TSH levels at L-T4 discontinuation were advantageous for successful withdrawal.

Congenital hypothyroidism (CH), characterized by insufficient thyroid hormone production due to abnormalities in the hypothalamic-pituitary-thyroid axis, is the most common congenital endocrine disorder. We previously conducted comprehensive genetic screening of 102 patients with permanent CH born in Kanagawa Prefecture, Japan and identified mutations in several genes in 19 CH patients, including defects in genes encoding dual oxidase 2, thyroglobulin, thyrotropin receptor, thyroid peroxidase, and paired-box 8. Despite these findings, approximately 80% of cases remain unexplained. CH pedigrees unexplained by known genetic forms of CH have been reported in the literature and registered as congenital hypothyroidism, nongoitrous, 3 (CHNG3; %609893) in Online Mendelian Inheritance in Man. We also identified a Japanese pedigree of CH that was compatible with CHNG3. However, the exact genetic cause of CHNG3 was not revealed by standard analysis methods such as exome sequencing and array comparative genomic hybridization. We therefore took a combined approach and analyzed a total of 11 undiagnosed CH pedigrees by whole genome sequencing to analyze a 3-Mb linkage region, and found a disease-causing variant affecting a TTTG microsatellite in a noncoding region on chromosome 15. Further analysis revealed that 13.9% of 989 Japanese CH patients had abnormalities involving the TTTG microsatellite, with a substantial proportion (41.5%) of familial CH cases carrying these mutations. Identification of the genetic cause of CHNG3 provides new insights into the pathogenesis of CH, and highlights the need for continued exploration of noncoding genomic regions in Mendelian disorders of unknown etiology.

Purpose: Short stature is the main characteristic of Turner syndrome (TS) patients and growth hormone (GH) therapy has been essential for achieving the final adult height (Ht). In the present study, the response of TS patients with different types of karyotype abnormalities to GH therapy was analyzed.

Methods: The clinical parameters of 194 TS patients registered in the LG Growth Study were retrospectively reviewed. Data for 4 groups of subjects were obtained as follows: monosomy X (n=56); X structural abnormality (n=26); X mosaicism without structural abnormality (n=41); X mosaicism with structural abnormality (n=71). Clinical characteristics and growth response parameters were compared over 3 years of GH treatment.

Results: The baseline Ht standard deviation score (SDS) of all patients was -2.85±0.86. The baseline Ht SDS, body mass index SDS, and chronological age (years)-bone age (years) were significantly different based on chromosomal abnormalities. The growth velocity (GV; cm/yr) in the first year was the highest and significantly different among the groups. The GV in the second year also showed an increase in the X mosaicism without structural abnormality group compared with the monosomy X group. The change in Ht SDS (ΔHt SDS) over 3 years was not statistically different between karyotypes.

Conclusion: The response to 3 years of GH therapy did not differ based on the karyotype of TS patients although the initial Ht SDS was the lowest in the monosomy X group.

Purpose: In this article, we report the results of a survey investigating post-coronavirus disease 2019 (COVID-19) syndrome in patients with type 2 diabetes mellitus and the impacts of vaccination on long-term manifestations. From February 2022 to April 2023, a survey of patients with type 2 diabetes and people without diabetes who were treated for a coronavirus infection was conducted in Kazakhstan.

Methods: Participants were invited via social media to voluntarily participate in this study. A total of 417 surveys were included in this study, comprising 212 patients with type 2 diabetes and 205 without diabetes. We compared persistent complaints after recovery in patients with and without diabetes mellitus (DM), as well as vaccination status.

Results: The results of this study on self-reported symptoms of prolonged COVID show that more than half of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Kazakhstan have at least one persistent symptom after recovery. Based on the list of prolonged COVID-19 symptoms reported by patients with type 2 DM (T2DM), exertional dyspnoea, fatigue, respiratory discomfort, headaches, and sleep disturbances are among the most common ongoing conditions, and in many cases last more than 3 months after COVID-19.

Conclusion: Patients with T2DM experience more severe and prolonged symptoms than those without diabetes. Additionally, vaccination lowers COVID-19 hospitalization risk and decreases the need for adjusting hypoglycemic therapy, such as insulin treatment, after recovering from SARS-CoV-2 infection.

Purpose: Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement.

Methods: We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS.

Results: At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST).

Conclusion: The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.