Effects of vitamin D supplementation on autoantibodies and thyroid function in patients with Hashimoto's thyroiditis: A systematic review and meta-analysis.

BACKGROUND: Hashimoto's thyroiditis (HT) is the prevailing form of autoimmune thyroiditis and the leading cause of hypothyroidism in iodine-sufficient regions worldwide. This study aims to evaluate the efficacy of vitamin D supplementation on HT through a meta-analysis of randomized controlled trials (RCTs). METHODS: The databases searched included PubMed, and others. We included RCTs that the treatment group received vitamin D, while the control group received either a placebo or no treatment. The studies measured the baseline and endpoint levels of 25-hydroxyvitamin D [25(OH)D], thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab). We performed a meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 12 studies involving 862 individuals were included. Vitamin D supplementation has a significant impact on reducing the titers of TPO-Ab (SMD = -1.084, 95% CI = -1.624 to -0.545) and TG-Ab (SMD = -0.996, 95% CI = -1.579 to -0.413) in patients with HT, and it also improves thyroid function by decreasing TSH level (SMD = -0.167, 95% CI = -0.302 to 0.031) and increasing FT3 (SMD = 0.549, 95% CI = 0.077-1.020) and FT4 (SMD = 0.734, 95% CI = 0.184-1.285) levels. Active vitamin D (calcitriol) significantly reduces the titer of TPO-Ab compared to naive forms of vitamin D (vitamin D2 or D3); treatment durations > 12 weeks result in a more effective reduction of TPO-Ab levels and a more significant increase in FT4 and FT3 levels in patients with HT (meta-regression P < .05). CONCLUSION: Vitamin D supplementation may have beneficial effects on HT patients by modulating immune responses and improving thyroid function.

Identification of Novel Compound Heterozygous Variants of the PNPLA6 Gene in Boucher-Neuhäuser Syndrome.

Background: Boucher-Neuhäuser syndrome (BNS, MIM 215470) is a rare autosomal recessive syndrome caused by mutations in the PNPLA6 gene. Few BNS cases have been reported for functional validation at the RNA level. Herein, we report on the family of a 17-year-old girl with clinical characteristics of BNS, genetic validation, and a systematic review of PNPLA6 variants related to BNS. Methods: Clinical data and blood samples were collected from the patient and their parents, and whole-exome sequencing was performed and confirmed by Sanger sequencing. RNA-sequencing (RNA-Seq) and quantitative RT-PCR (qRT-PCR) were performed, and the three-dimensional protein structures of the variants were predicted. Results: We report a 17-year-old female with progressive night blindness since the age of four, primary amenorrhea, and non-development of secondary sexual characteristics. Her impaired vision was diagnosed as retinal pigmentary degeneration of the retina. She had congenital hypogonadotropic hypogonadism (CHH) but no cerebellar ataxia at present. Two novel compound heterozygous variants (c.2241del/p.Met748TrpfsTer65 and c.2986A>G/p.Thr996Ala) of the PNPLA6 gene (NM_006702.4) were identified by whole-exome sequencing. The former variant was carried from her healthy father and has not been reported previously. The latter was inherited from her healthy mother and was noted in a report without functional studies. The RT-PCR results showed that the mRNA expression of PNPLA6 was lower in this patient and her father than in the control group. She was diagnosed with BNS. Both variants (c.2241del and c.2986A>G) were likely pathogenic according to the ACMG criteria. The novel variants in the PNPLA6 gene related to Boucher-Neuhäuser syndrome were summarized in this article. Conclusion: The possibility of Boucher-Neuhäuser syndrome should be considered when patients present with night blindness, impaired vision, and hypogonadotropic hypogonadism. Gene sequencing is currently the primary diagnostic method. Herein, novel compound heterozygous variants of PNPLA6 were identified in a BNS patient, and its function was verified at the RNA level. The PNPLA6 c.2241del variant is novel and potentially pathogenic, expanding the mutation spectrum in PNPLA6.