Genome-wide DNA methylation analysis of Hashimoto's thyroiditis during pregnancy
FEBS OPEN BIO
Authors: Wenqian, Cai; Fan, Wenlei; Hu, Xijiang
Hashimoto's thyroiditis (HT) during pregnancy is usually accompanied by an elevation of thyroid-stimulating hormone and a reduction of serum-free thyroxine during gestation, which may lead to abortion, preterm delivery, and reduced intellectual function of the offspring. Epigenetic alterations may provide important insights into genetic-environmental interactions in HT. Here, we examined global DNA methylation patterns in patients with HT during pregnancy. DNA was extracted from 13 women with HT during pregnancy (HTDP) and eight healthy pregnant women as a control group. Genome-wide methylation was detected with the use of an Illumina Human Methylation 850K Beadchip. A total of 652 differentially methylated positions (DMPs) and 27 differentially methylated regions (DMRs) were identified between the HTDP and control groups. GO analysis revealed that DMPs were significantly enriched in 540 GO terms, which included regulation of the differentiation of keratinocytes, T helper cell differentiation, and alpha-beta T-cell differentiation. Moreover, significant enrichment of KEGG pathways of the DMPs included mucin-type O-glycan biosynthesis, focal adhesion, and the insulin signaling pathway. The GO items associated with DMRs included muscle cell proliferation, response to biotic stimulus, anatomical structure formation involved in morphogenesis, and genes primarily involved in the FoxO signaling pathway. Finally, the DTNA gene was identified as the seed gene of functional epigenetic modules. In summary, the DNA methylation pattern of the HTDP group was distinct from that of the control group, and thus, changes in DNA methylation may influence the development of HT by regulation of the autoimmunity process.
L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms Secondary Analysis of a Randomized Trial
ANNALS OF INTERNAL MEDICINE
Authors: de Montmollin, Maria; Feller, Martin; Beglinger, Shanthi; McConnachie, Alex; Aujesky, Drahomir; Collet, Tinh-Hai; Ford, Ian; Gussekloo, Jacobijn; Kearney, Patricia M.; McCarthy, Vera J. C.; Mooijaart, Simon; Poortvliet, Rosalinde K. E.; Quinn, Terence; Stott, David J.; Watt, Torquil; Westendorp, Rudi; Rodondi, Nicolas; Bauer, Douglas C.
Background: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit. Objective: To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden. Design: Secondary analysis of the randomized, placebocontrolled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126) Setting: Switzerland, Ireland, the Netherlands, and Scotland. Participants: 638 persons aged 65 years or older with persistent SCH (thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for >3 months and normal free thyroxine level) and complete outcome data. Intervention: L-thyroxine or matching placebo with mock dose titration. Measurements: 1-year change in Hypothyroid Symptoms and Tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire among participants with high symptom burden (baseline Hypothyroid Symptoms score >30 or Tiredness score >40) versus lower symptom burden. Results: 132 participants had Hypothyroid Symptoms scores greater than 30, and 133 had Tiredness scores greater than 40. Among the group with high symptom burden, the Hypothyroid Symptoms score improved similarly between those receiving L-thyroxine (mean within-group change, -12.3 [95% CI, -16.6 to -8.0]) and those receiving placebo (mean within-group change, -10.4 [CI, -15.3 to -5.4]) at 1 year; the adjusted between-group difference was -2.0 (CI, -5.5 to 1.5; P = 0.27). Improvements in Tiredness scores were also similar between those receiving L-thyroxine (mean within-group change, -8.9 [CI, -14.5 to -3.3]) and those receiving placebo (mean within-group change, -10.9 [CI, -16.0 to -5.8]); the adjusted between-group difference was 0.0 (CI, -4.1 to 4.0; P = 0.99). There was no evidence that baseline Hypothyroid Symptoms score or Tiredness score modified the effects of L-thyroxine versus placebo (P for interaction = 0.20 and 0.82, respectively). Limitation: Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data. Conclusion: In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo.