Context There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. Objective This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. Methods Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography–mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. Results A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. Conclusion Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

NARS2 mutations are known to cause various clinical phenotypes such as nonsyndromic hearing loss, Leigh/Alpers syndrome, refractory epilepsy, developmental delay, intellectual disability and myopathy. We presented the first Turkish variant of NASR2 and added type 1 diabetes mellitus (DM), which was not previously described in the phenotype spectrum of this disease. A 4.5-month-old girl presented with hearing loss, hypotonia, refractory myoclonic epilepsy, severe developmental delay and large subdural hemorrhage. In the first year of the follow-up, type 1 DM developed. A homozygous missense mutation, [c.500 A>G, p.H167R] in the NARS2 gene was detected in the trio-based whole-exome sequencing (WES). In this disease, in addition to multi-organ involvement, type 1 DM may also develop, as in our case. Since it is a mitochondrial disease, the decision to treat with valproic acid should be reconsidered. The long diagnostic process can be shortened with WES.

Background: Gut microbiota studies in the field of endocrinology metabolism have attracted increasing attention in recent years. To comprehensively assess the evolving landscape of this research field, we conducted a thorough bibliometric analysis of gut microbiota studies in endocrinology metabolism indexed in the Web of Science database.Methods: We collected and analyzed 3,339 original research articles and reviews published from 1972 to 2023. Using various bibliometric indicators, we investigated publication trends, country contributions, international collaborations, prolific authors, top journals, and influential articles.Results: Our analysis revealed a significant upsurge in publications after 2010, indicating a growing scientific interest in microbiota and endocrinology metabolism. Keyword and thematic analyses have identified gut microbiota, obesity, diabetes, and inflammation as core research themes. Additionally, the roles of probiotics and prebiotics are increasingly researched for their therapeutic effects in shaping the microbiota.Conclusion: This study reveals that research in endocrinology metabolism is increasingly decoding the connection between gut microbiota and diseases. There’s also a growing focus on microbiota manipulation, which points to a shift towards personalized medicine. Future research should focus on integrating these findings into clinical practice, moving from lab-based studies to real-world patient care.

Introduction: Vitamin D binding protein (VDBP) plays a crucial role in vitamin D transport and metabolism. The rs4588-A polymorphism of the GC gene, encoding VDBP, has been associated with altered serum VDBP and 25-hydroxyvitamin D (25OHD) levels. However, the mechanisms underlying these effects remain unclear. We aimed to investigate the relationship between urinary VDBP excretion and serum VDBP and 25OHD levels in individuals with and without the rs4588-A allele.Methods: A cross-sectional study was conducted on 109 children (mean age: 11.96 years) to explore the impact of rs4588-A on vitamin D metabolism and urinary VDBP excretion. Biochemical analyses determined serum 25OHD and VDBP levels, and urinary VDBP-to-creatinine ratio (u-VDBP/Cr). Genotyping for rs4588 SNP was performed using LightSNiP assay. Statistical analyses included correlation, linear regression, and comparison between allele groups.Results: Participants carrying the rs4588-A allele exhibited lower serum 25OHD levels compared to non-carriers (median (IQR): 11.85 (3.5) vs. 12.86 (4.9), p = 0.023). However, no statistically significant differences were observed in serum VDBP levels (126.34 ± 59.3 in rs4588-A vs. 136.49 ± 51.3 in non-rs4588-A, p = 0.141) or in u-VDBP/Cr (median (IQR): 0.4 (0.35) in rs4588-A vs. 0.386 (0.43) in non-rs4588-A, p = 0.189) between the two allele groups. A significant inverse correlation between u-VDBP/Cr and serum VDBP levels was found only in rs4588-A carriers (r = -0.367, p = 0.024). No such correlation was observed in non-carriers or the entire cohort. A linear regression analysis confirmed the impact of u-VDBP/Cr on serum VDBP levels in rs4588-A carriers (B = -0.269, t = -2.185, p = 0.035).Conclusion: Individuals with the rs4588-A allele in the GC gene had lower serum 25OHD levels. An inverse correlation between urinary VDBP excretion and serum VDBP levels was observed, suggesting a partial role of the renal pathway in altered serum VDBP and 25OHD levels linked to the rs4588-A allele.

Abetalipoproteinaemia is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride. It results from mutations in the gene encoding microsomal triglyceride transfer protein. Nine-month-old girl was admitted to our hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and triglycerides levels according to her age. The peripheral blood smear revealed acantocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and the pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p. D169V)] was detected in MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of abetalipoproteinaemia and central hypothyroidism was not previously reported in another case. A homozygous novel mutation [c.506A>T (p. D169V)] was detected in MTTP gene.

Endocrine-disrupting chemicals (EDCs) are environmental contaminants that disrupt hormonal regulation by mimicking, inhibiting, or modifying endocrine signaling pathways. EDCs are commonly present in plastics, pesticides, industrial byproducts, and personal care products and pose substantial health risks, particularly to vulnerable groups such as infants and children. Early-life exposure is especially concerning due to the developing detoxification systems, the immaturity of the blood–brain barrier, and the ongoing organ differentiation, making these periods highly susceptible to EDCs’ harmful effects. Moreover, exposure during critical developmental periods, such as sex differentiation and neurodevelopment, can lead to significant long-term developmental impairments that persist into later life.Perinatal and childhood exposure to EDCs has been linked to various adverse health outcomes, including neurodevelopmental delays, impairments in reproductive health, obesity, type 2 diabetes, thyroid dysfunction, and even a heightened risk of certain malignancies. These effects are mediated through various mechanisms, including direct modulation of hormone receptors, disruption of genetic regulation, and interference with endocrine feedback systems. Alterations in endocrine signaling, particularly disruptions in thyroid hormone homeostasis, may also indirectly impair cognitive development, increasing the risk of attention disorders and intellectual impairment.Although regulatory measures to reduce EDC exposure are crucial, current restrictions remain insufficient. Moreover, as new EDCs emerge, ongoing research is essential to understand their risks and develop effective strategies to minimize their potential harm. Protecting future generations requires a proactive approach that combines public health awareness, strong regulations, and ongoing scientific research. This review highlights the potential risks of EDCs exposure in children and highlights the significance of multidisciplinary research and policy efforts.