Journal of Clinical Research in Pediatric Endocrinology最新文献

Objective: Endocrine findings in premature adrenarche have been characterized by elevated dehydroepiandrosterone (DHEA) DHEA-sulfate (DHEA-S) levels in the past.

Methods: We reviewed female patients, aged 4 to 8 years, with premature adrenarche who were seen at a single center between 2019 and 2023. Data were collected on the traditional androgens (DHEA and DHEA-S) and novel 11-oxo-androgens, which were measured using liquid chromatography/tandem mass spectrometry assays in commercial laboratories (Lab Corp).

Results: The study included 44 girls. The majority, 89% of patients from the youngest group (4-5 years olds), presented with apocrine odor as the only symptom of premature adrenarche. We have demonstrated that DHEA and DHEA-S levels were within the normal range in many girls with premature adrenarche, whereas 11-oxo-androgens, particularly 11-hydroxyandrostenedione and 11-beta-hydroxytestosterone, were elevated. Out of those with normal DHEA-S, 75% had elevated 11-hydroxyandrostenedione, and 77.8% of those patients with normal DHEA had the same elevated oxo-androgen. Moreover, advanced bone age greater than 1 year compared to chronological age was positively associated with 11-ketotestosterone [Spearman rho=0.32, 95% confidence interval (CI): 0.01-0.57, p=0.0429] and 11β-hydroxy testosterone (Spearman rho=0.32, 95% CI: 0.01-0.58, p=0.0395).

Conclusion: We propose that 11-oxo-androgens are a more sensitive steroid to be measured when premature adrenarche is suspected.

Objective: The management of type 1 diabetes (T1D) in children aims to achieve an hemoglobin A1c (HbA1c) of <7%, a good quality of life and a life similar to that of their peers. While the HbA1c <7% target may be difficult to achieve, it is possible that national programs, quality control programs and setting team targets can achieve significant reductions in HbA1c.

Methods: The records of children with T1D followed up in our department between 2020 and 2022 were analyzed. Children and their families received a comprehensive education including an “Individual Treatment Plan”, nutrition and carbohydrate counting. All HbA1c measured during follow-up were averaged for each child separately. Continuous glucose monitoring (CGM) data from the last visit was evaluated in terms of achieving CGM consensus targets. To assess the effect of CGM use and automated insulin delivery (AID) system use, subjects were divided into 3 groups as multiple dose insulin and CGM users, non-AID pump users and AID users and evaluated.

Results: The 480 children included in the study had a mean HbA1c of 7.8±1.5% at the first visit. The median HbA1c value during the two-year follow-up was 7.1%. Of the participants, 43% had an HbA1c <7%. Evaluating cases by treatment modalities and glucose measurement methods revealed that AID users having the lowest mean HbA1c (7±0.7%).

Conclusion: While diabetes technologies have significantly improved T1D treatment, we believe that holistic approaches focusing on patient behaviors, comprehensive education, teamwork, written individualized treatment plans, and tighter metabolic goals are effective in achieving better glycemic outcomes.

Objective: Mandibuloacral dysplasia (MAD) is a rare genetic disorder characterized by distinctive skeletal abnormalities, metabolic issues, and skin changes, often linked to pathogenic variants in the LMNA gene, which encodes lamin A/C. This study investigates a specific founder mutation within a Turkish cohort and explores its impact on phenotypic expressivity.

Methods: We conducted a comprehensive analysis involving genetic testing for LMNA variants in patients diagnosed with MAD. Clinical evaluations documented a wide range of phenotypic features, including facial dysmorphism, skeletal anomalies, and metabolic abnormalities. We also collected family histories to assess inheritance patterns and potential environmental influences.

Results: Our findings identified a common founder mutation in the LMNA gene among the cohort, which was present in a significant percentage of participants. Notably, phenotypic expressivity varied significantly, with some individuals exhibiting classic MAD features, while others showed atypical manifestations, such as additional endocrine disorders and variable severity of skeletal anomalies. This variability underscores the complexity of the genotype-phenotype relationship.

Conclusion: This study highlights the significance of the founder mutation in LMNA and its diverse phenotypic outcomes in MAD. Our results contribute to the understanding of how genetic mutations can lead to a spectrum of clinical presentations, emphasizing the necessity for personalized clinical approaches in managing this condition. Further research is warranted to elucidate the underlying mechanisms of phenotypic variability and to improve diagnostic and therapeutic strategies.

Schwartz-Jampel syndrome (SJS) type 1 (OMIM; #255800), a rare cause of skeletal dysplasia, is characterized by myotonic myopathy, chondrodystrophy, short stature, facial and eye abnormalities. SJS type 1 develops due to variations in the HSPG2 gene which produces the “perlecan” molecule, one of the main proteoglycans of the basement membrane. A 6-year-old girl presented with short stature, a mask face, shrunken lips, narrow palpebral opening due to blepharospasm, stiffness of facial muscles, micrognathia, overlapping teeth, a short neck, and a bell-shaped thorax due to myotonic myopathy. She was diagnosed with SJS type 1 due to compound heterozygosity of two novel variations in the HSPG2 gene. In patients with short stature and an accompanying myotonic myopathy SJS should be considered. Compound heterozygosity may cause typical clinical findings of SJS. In case of suspicion creatinine kinase levels can be measured, and the determination of myotonia may require evaluation with electromyography. Once the diagnosis is made, patients should be carefully monitored in terms of growth, neuromuscular disorders, joints problems and bone health.

Objective: Adults with classical congenital adrenal hyperplasia (CAH) exhibit a higher lifetime prevalence of depression, but little is known about onset or etiology of mood disorders in this population. We therefore aimed to assess depression in youth with CAH, compared to controls, using the Children’s Depression Inventory (CDI).

Methods: Youth with classical CAH due to 21-hydroxylase deficiency and age- and sex-matched controls completed the CDI and had analyte and genetic testing.

Results: A total of 31 patients with CAH and 36 controls were included. Youth with CAH exhibited CDI measures that differed significantly by glucocorticoid dose and type. For glucocorticoid dose, significant correlations were found between CDI total T-score (r=0.42, p<0.05), as well as multiple subscores. Dose also predicted total T-score (β=1.75), Emotional-Problems (β=1.41), Negative-Self-Esteem (β=1.91), Functional-Problems (β=1.90), Ineffectiveness (β=1.56), and Interpersonal-Problems (β=2.11) (all p<0.01). For glucocorticoid type [dexamethasone n=7, hydrocortisone (HC) n=24], scores were higher in patients treated with dexamethasone for total T-score [dexamethasone: 59 (53.5-72), HC: 50 (43.75-55.75)], Emotional-Problems [dexamethasone: 63 (51.0-67.0), HC: 45 (42.0-56.5)], and Negative-Self-Esteem [dexamethasone: 53 (50.0-73.5), HC: 44 (44.0-51.0)] (all p<0.05).

Conclusion: Higher HC doses and use of dexamethasone were both found to be associated with higher CDI scores in children and adolescents with classical CAH.

21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH). Salt-wasting CAH can present with life-threatening salt-wasting crises, underscoring the importance of universal newborn screening. We present a patient diagnosed with classical CAH despite four negative newborn screen results (NBS) results. A male infant was born at 35 weeks gestation with birthweight 1470 grams following signs of placental insufficiency. While hospitalized in the neonatal intensive care unit (NICU), four NBS samples from days of life 2 to 38 were all within normal range, including on repeat analysis via fully integrated fluoroimmunoassay. After initially normal biochemical testing, hyponatremia and hyperkalemia developed by day of life (DOL) 26, responsive to sodium chloride supplementation. Following recurrent hyponatremia after trial off supplementation after day of life 50, 17-hydroxyprogesterone as measured via liquid chromatography-tandem mass spectrometry were reported at two different labs as 10,900 ng/dL and 11,200 ng/dL (<2 ng/dL at 50 DOL). Subsequent testing identified deletion of one CYP21A2 allele and a I172N mutation in the second. This report illustrates the importance of maintaining a high index of suspicion for classic forms of CAH in infants with persistent electrolyte disturbances despite negative NBS results.

Primary adrenal insufficiency (PAI) in childhood is a rare and potentially life-threatening condition that may arise from defects in adrenal steroidogenesis, adrenal dysgenesis, ACTH resistance, autoimmune mechanisms, or inherited metabolic disorders. Among the latter, peroxisomal dysfunctions represent a rare cause. Although X-linked adrenoleukodystrophy is a well-recognized etiology, adrenal involvement in other peroxisomal diseases, such as ACOX1 deficiency, remains poorly defined. We report a three-year-old girl with global developmental delay, epilepsy, bilateral sensorineural hearing loss, and progressive neurological regression. Biochemical analyses revealed abnormal plasma very-long-chain fatty acids profile, suggesting a peroxisomal disorder. Whole-exome sequencing identified a homozygous pathogenic variant (c.1478+2T>A) in ACOX1, confirming the diagnosis of pseudo-neonatal adrenoleukodystrophy. During hospitalization for a urinary tract infection, endocrine evaluation revealed markedly elevated plasma ACTH (529 pg/mL) and low serum cortisol (8.62 µg/dL), while Na, K, and PRA were within normal limits. Adrenal imaging was consistent with atrophy. Hydrocortisone replacement was initiated with good clinical response. Notably, the patient had no classical signs of adrenal failure such as hyperpigmentation or electrolyte imbalance. This case provides additional evidence that ACOX1-related Pseudo-neonatal adrenoleukodystrophy may be associated with variable adrenal involvement, expanding the phenotypic spectrum of the disorder. The absence of typical clinical manifestations highlights the importance of routine hormonal screening in children with peroxisomal diseases, even in the absence of overt adrenal symptoms. Early recognition of endocrine dysfunction can prevent life-threatening adrenal crises and offers valuable insight into the broader pathophysiology of peroxisomal β-oxidation disorders.

Objective: Reduced sleep quality in children has been associated with obesity and fatty liver disease; however, there are no studies evaluating the impact of gastrointestinal symptoms on sleep quality in children with metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this cross-sectional study was to investigate the prevalence of gastrointestinal symptoms and sleep disturbances in children with MASLD and to examine the association of gastrointestinal symptoms with sleep disturbances.

Methods: Anthropometric and biochemical examinations were performed on 176 children aged 8-18 years (84 children with MASLD and 92 healthy controls). The Hepatic Steatosis Index (HSI) and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated for children with MASLD. Sleep disturbances were assessed using the Child Sleep Habits Questionnaire (CSHQ), and gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Logistic regressions were used to examine factors associated with sleep quality.

Results: A total of 123 participants (69.9%) had sleep disturbances. In unadjusted analysis, sleep disturbances were significantly more common in the MASLD group (89% vs 57%, p<0.001). However, in the final multivariate regression model adjusting for metabolic confounders, the independent predictors of sleep disturbances were low family income (Odds Ratio [OR]=9.56, 95% Confidence Interval [CI]=2.80-32.57), total GSRS score (OR=1.15, 95% CI=1.06-1.24), and HOMA-IR (OR=1.51, 95% CI=1.01-2.27). The presence of MASLD itself lost statistical significance after adjustment (p=0.554). NFS, a marker of fibrosis risk, was associated with both sleep disturbances and gastrointestinal symptoms.

Conclusion: This study shows that sleep disturbances and gastrointestinal symptoms are more common in children with MASLD, and that gastrointestinal disturbances are significantly associated with sleep disturbances. Furthermore, the results suggest that sleep disturbances may be more common in children with MASLD who have a higher estimated risk of liver fibrosis. Children with MASLD should be evaluated not only for liver health but also for extrahepatic conditions, including sleep and gastrointestinal disorders.

Objective: This study aims to investigate the frequency of skin, hair, nail, and mucosal findings in children with Turner Syndrome (TS) and their associations with coexisting endocrinopathies.

Methods: A cross-sectional study was conducted on 112 TS patients who were followed up by pediatric endocrinology and referred to the dermatology outpatient clinic. Data were collected using standardized dermatological examination forms, including demographic information, clinical features, presence of endocrinopathies, and medication usage. The SPSS software was used to evaluate differences between groups and to analyze relationships between variables.

Results: Skin and hair findings were detected in 86.6% of the patients, with melanocytic nevi (44.6%) and xerosis (41.1%) being the most commonly observed. Oral mucosal findings were observed less frequently (17.0%). Nail findings were detected in 63.4% of the cases, with leukonychia (15.2%) and subungual hyperkeratosis (14.3%) being the most prevalent. Older age, delayed diagnosis, longer follow-up duration, and lower body mass index were associated with an increased frequency of skin and hair findings (p < 0.05). Additionally, the presence of coexisting endocrinopathies was significantly associated with skin and hair findings. Nail findings were significantly associated with longer follow-up duration (p = 0.002), the presence of endocrinopathies (p < 0.001), and comorbidities (p = 0.004).

Conclusion: This study revealed that skin, hair, and nail abnormalities are commonly observed in Turner Syndrome. The association of these findings with endocrinopathies suggests that systemic factors influence dermatological problems in TS. It is recommended to integrate dermatological evaluations into the routine endocrine and cardiological follow-up of children with Turner Syndrome.