Central precocious puberty in a boy with X-linked adrenoleukodystrophy caused by a novel ABCD1 mutation.

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic disorder caused by pathogenic variants in the ABCD1 gene. The symptoms include primary adrenal insufficiency (PAI), progressive spinal cord disease, inflammatory demyelinating cerebral disease, and primary hypogonadism. It is exceptionally rare that pediatric PAI is accompanied by central precocious puberty (CPP). The purpose of this study was to better understand the diversity of clinical manifestations of X-ALD and to identify the ABCD1 gene mutation in a case of a boy with X-ALD accompanied by CPP. We collected clinical, laboratory and imaging data, and used whole-exome sequencing (WES) analysis to evaluate the pathogenicity of the variant. We also predicted the potential deleterious effects of the novel mutation using Mutation Taster and generated three-dimensional protein structures using Swiss-Model and PyMOL Viewer software. The patient presented with PAI accompanied by CPP. Adrenal gland CT revealed adrenal hypoplasia. Gonadotropin-releasing hormone stimulation tests revealed CPP. WES revealed a novel variant (c.1376dup) in the ABCD1 gene, which resulted in a reading frameshift and a premature termination codon (p.Leu461ProfsTer95). Sanger sequencing confirmed that the variant was inherited from his heterozygous mother. Mutation Taster predicted that the variant could be harmful. The overall three-dimensional structures of the mutant wild-type proteins were visually distinct. Our results shed light on additional aspects of X-ALD. The premature activation of the hypothalamic-pituitary-gonadal axis may possibly be related to the pathogenic ABCD1 gene mutation.

Thyroid function in children with short stature accompanied by isolated pituitary hypoplasia.

PURPOSE: Few studies have focused on thyroid function in children with isolated pituitary hypoplasia (IPH). The purpose of this study was to investigate thyroid function in children with short stature accompanied by IPH and evaluate the values of thyroid function for the diagnosis of IPH. METHODS: This was a retrospective observational study. A total of 100 children with short stature accompanied by IPH were enrolled. Among them, 68 children presenting with isolated growth hormone deficiency (IGHD) were chosen as the IPH group. Sixty-eight age-matched and sex-matched IGHD children without pituitary abnormalities were chosen as the control group. Clinical, hormonal, and imaging parameters were analyzed. The diagnostic value of thyroid function for IGHD children with IPH was evaluated. RESULTS: Children in the IPH group had significantly lower height standard deviation score (HSDS), HSDS-target height standard deviation score (THSDS), free thyroxine (FT4), insulin-like growth factor-1 standard deviation score (IGF-1SDS), and pituitary height than the control subjects (p = 0.027, p = 0.033, p < 0.001, p = 0.03, and p < 0.001, respectively). The value of the area under the curve (AUC) was 0.701 (95% CI 0.614-0.788, p < 0.001) when the cut-off value for FT4 was ≤ 16.43 pmol/L and the sensitivity and specificity were 72.1 and 61.8%, respectively. FT4 levels were positively correlated with FT3, GH peak, and IGF-1 SDS levels in all children with short stature accompanied by IPH (p < 0.001, p = 0.009, and p = 0.01, respectively). CONCLUSION: IGHD children with IPH had lower FT4 levels than IGHD children without pituitary abnormalities. FT4 levels may have diagnostic value for IGHD children with IPH.

Effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with graves' disease.

BACKGROUND: Glucocorticoid treatment is used in children with Graves' disease (GD) only in cases of exophthalmos. The purpose of this study was to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with GD. METHODS: Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30 days, and 60 days after treatment. RESULTS: Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in the pulse group and the control group from baseline to follow-up time points (all p < 0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (p = 0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the pulse group and the control group (all p > 0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the pulse group and the control group (all p > 0.05). CONCLUSIONS: The results suggested that the effect of intravenous MPT followed by oral prednisolone on TRAb level was temporary in children with GD. Glucocorticoid pulse therapy was not beneficial for the sustained recovery of thyroid function.

Angelica polysaccharide moderates hypoxia-evoked apoptosis and autophagy in rat neural stem cells by downregulation of BNIP3.

Neonatal hypoxia-ischemia is a troublesome disease. Angelica polysaccharide (AP) is proved to have antioxidant effects. Our study was performed to confirm the effects of AP in hypoxia-exposed neural stem cells (NSCs). NSCs were pre-treated with AP and then stimulated with hypoxia. Viability of NSCs was examined by Cell Counting Kit-8 assay. Hypoxia-introduced apoptosis was observed by flow cytometry. Essential regulators of mTOR and Notch signalling pathways were examined by Western blot. mRNA expression was accessed using qRT-PCR. Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) was altered by transfection. We noticed that NSCs were sensitive to hypoxia-induced apoptosis and showed decreased viability. Moreover, Beclin and light chain 3-II was upregulated while p62 was downregulated. However, AP reversed all these results. Similarly, hypoxia decreased the phosphorylation of mTOR and p70S6K and Notch1 expression while AP increased the phosphorylation of mTOR and p70S6K as well as the expression of Notch1. BNIP3 was upregulated by hypoxia while downregulated by AP. Further experiments demonstrated that overexpression of BNIP3 broken all the effects induced by AP shown in cell viability, apoptosis, autophagy and signalling pathways. Collectively, AP alleviated hypoxia-introduced NSCs damages by maintaining cell viability, blocking apoptosis and autophagy via downregulation of BNIP3 with the activation of mTOR and Notch signalling pathways.