Journal of Clinical Research in Pediatric Endocrinology最新文献

Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves’ disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts (CBC) monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of CBC may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.

Objective: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy.

Methods: Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure.

Results: A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001).

Conclusion: Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D.

In terms of prevalence, 11β-hydroxylase deficiency (11β-OHD), a common form of congenital adrenal hyperplasia, closely follows 21-hydroxylase deficiency. 11β-OHD has been attributed to diminished enzymatic activity owing to CYP11B1 gene variants, mainly encompassing single nucleotide variations and insertions-deletions. The involvement of chimeric CYP11B2/CYP11B1 genes in 11β-OHD has rarely been reported. We conducted a genetic investigation on a male infant with generalized pigmentation and abnormal steroid hormone levels. Whole-exome sequencing revealed a heterozygous variant in CYP11B1 inherited from the mother (NM_000497.4: c.1391_1393dup [p.Leu464dup]). Long-range polymerase chain reaction revealed an additional allele, a chimeric CYP11B2/CYP11B1 gene, inherited from the father. The current case report highlights the need to consider the occurrence of gene fusion variants in the diagnosis of neonatal or early infantile 11β-OHD.

Phosphate has a fundamental role in bone mineralization, and its chronic deficiency has multiple negative consequences in the body, including defects in bone mineralization that will manifest in children as rickets and osteomalacia. Here we present a young boy known to have Wiedemann-Steiner syndrome with multiple co-morbidities that necessitated gastric tube feeding. The child at 22 months was found to have hypophosphatemia and a high alkaline phosphatase level associated with rachitic skeletal manifestations that were attributed to low phosphate intake and/or gastrointestinal absorption, as there was no evidence of excessive phosphate wasting based on appropriate tubular renal re-absorption of phosphate. The primary nutritional source was an elemental amino acid-based milk formula (Neocate^®) from 12 months of age. After switching from Neocate^® to another elemental amino-acid based milk formula, all biochemical and radiological abnormalities returned to normal, indicating that the Neocate^® formula was the possible cause of the patient’s low phosphate intake. However, in the literature, this formula-associated effect was only described in a limited number of patients. Whether or not some patient-related factors, such as the very rare syndrome described in our patient, could influence this effect warrants further exploration.

Objective: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population.

Methods: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R² values in SNP paired combinations.

Results: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799.

Conclusion: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Background: Excessive iodine intake triggers the Wolff-Chaikoff effect resulting in downregulation of thyroid hormone synthesis to prevent hyperthyroidism. Failure to escape the Wolff-Chaikoff effect can be seen especially in (premature born) infants and may result in prolonged iodine induced hypothyroidism. We describe a rare case of a preterm infant who developed severe iodinated contrast induced hypothyroidism after the use and prolonged stasis of enteral iodinated contrast media (ICM). In addition a systematic literature search was performed to evaluate all available data on this complication.

Methods: A systematic literature search was performed in PubMed and Embase. Studies describing the effect of enteral ICM on thyroid function were considered eligible. The primary outcome was to determine the frequency of contrast induced hypothyroidism in infants after administration of enteral ICM.

Results: The premature infant in our center developed severe iodinated contrast induced hypothyroidism after enteral ICM. In total, only two studies met our eligibility data, reporting eight patients. Out of these eight patients, four premature infants developed a contrast induced hypothyroidism after enteral administration of ICM.

Conclusion: Data on severity, length and frequency of contrast induced hypothyroidism after exposure to enteral ICM is very scarce. The herein reported case and literature search illustrate the potential severity of the complication and underline the necessity of future studies on this topic. We recommend standardized monitoring of thyroid function after exposure to enteral ICM in newborns to prevent delayed diagnosis of severe contrast induced hypothyroidism until evidence based recommendations can be made.

Schimke Immuno-Osseous Dysplasia (SIOD) (MIM:242900) is an ultra-rare autosomal recessive pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency and spondyloepiphyseal dysplasia and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia and elevated FSH levels. Karyotype analysis and array-CGH testing were normal. Clinical Exome Sequencing was performed via next-generation sequencing to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during her follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious spondyloepiphyseal dysplasia was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. One hundred twenty-five SIOD cases from 38 literature reporting SMARCAL1 gene pathogenic variants were reviewed to investigate whether hypercalcemia, hypophosphatemia and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first time these findings had been reported in a SIOD patient. This report expands not only the phenotypic but also genotypic spectrum of SIOD.

Objective: To study the national incidence of admission for diabetic ketoacidosis (DKA) in Thai children and adolescents with type 1 diabetes (T1D) and characterize risk factors for DKA admission.

Methods: Admission records of children and adolescents with T1D during the years 2015-2019 were retrieved from the Thai health coverage system of all schemes. Hospitalization was categorized according to patients' age groups (<1, 1-5, 6-12 and 13-17 years), sex and geographical regions (Bangkok, Central, Northeast, North and South). DKA admission incidence and rate were calculated and compared among subgroups.

Results: The annual incidences of T1D and DKA admissions progressively increased over the study period (T1D: 12.0 to 15.0, p<0.001 and DKA: 4.8 to 7.3 per 100,000 child-years, p<0.001). About half of DKA admissions (52%) were recurrent episodes. DKA admission rate was 1.49 admissions/patient. The incidence of DKA admission was greatest in individuals aged 13-17 years (13-17 years: 10.3; 6-12 years: 6.3; 1-5 years: 1.7; and <1 year: 0.6 per 100,000 child-years, p<0.001). DKA admission incidence was greater in females than males (7.6 vs. 4.3 per 100,000 child-years, p<0.001). Among 5 geographical regions, greatest percentage of recurrent DKA (57%), rate of increased annual incidence of DKA admission (3.8 to 7.8 per 100,000 child-years), and DKA admission rate (1.64 admissions/patient) were found in the Northeast region.

Conclusions: During the years 2015-2019, rising annual incidences of T1D and DKA admissions among Thai youth were observed. Individuals older than 6 years, being females, and resided in the Northeast region had higher risk for DKA hospitalization.

Objective: Endocrine abnormalities may represent the only clinical manifestation of primary mitochondrial disorders. This study aimed to evaluate the endocrinological characteristics of mitochondrial disease in our cohort.

Methods: A total of twenty-six pediatric patients diagnosed with mitochondrial disease were categorized on the basis of their specific genetic abnormalities. The auxologic data, pubertal development, and, based on their clinical symptoms, hormonal profiles were obtained.

Results: Twelve of the cohort of 26 patients (46%) were female. In 15 of the patients (57.6%), their mitochondrial disease (MD) was caused by nuclear DNA mutations (nDNA group). Four patients had Leigh syndrome, 2 patients had LHON syndrome, 2 patients had MELAS, and 1 patient had KSS clinical phenotype. The median age at diagnosis was 2.91 (0.59-16.8) years, and the median age at first endocrinologic evaluation was 4.62 (1.26-18) years. The mean height SDS was -1.34 ± 2.12, and the mean BMI SDS was -0.82 ± 1.96 for all patients. Of the 26 patients, 6 (23%) had a range of hormonal deficits. Ovarian insufficiency, central adrenal insufficiency, central hypothyroidism, diabetes mellitus, and critical illness-related adrenal insufficiency were all observed. Three of the patients were initially monitored in the endocrine clinic for hormone deficiencies but it was later determined that the hormonal abnormalities were caused by underlying mitochondrial disease.

Conclusion: Individuals diagnosed with mitochondrial disease, particularly those with specific genetic abnormalities, are considered a high-risk group for developing hormonal deficits. Endocrine diseases could be one of the primary mitochondrial disorders' early warning symptoms.