Journal of Clinical Endocrinology & Metabolism最新文献

Context: Accurate assessment of the inflammatory status in thyroid eye disease (TED) is crucial for diagnosis and treatment; however, this assessment remains challenging.

Objectives: To study whether thyrotrophin receptor antibody (TRAb) can be utilized as a quantitative and objective indicator of the inflammatory status in patients with TED.

Methods: We gathered and analyzed TRAb and clinical characteristics from 226 consecutive TED patients. Additionally, we examined 27 inflammatory cytokines in the orbital adipose tissue of 41 patients and assessed the alterations in TRAb following IV methylprednisolone (IVMP) therapy in 40 patients.

Results: The 226 TED patients included 116 females and 110 males, with a mean age of 46.4 ± 12.2 years. The correlation between TRAb and clinical activity score (CAS) was the most pronounced (r = 0.427; P < .001). TRAb was identified as the most influential factor for CAS. Subsequent investigation into the relationship between TRAb and pathological inflammation revealed that TRAb exhibited a significant positive correlation with 7 proinflammatory cytokines [Interleukin (IL)-8, chemokine (C-C motif) ligand 3 (CCL-3), serpin E1, platelet-derived growth factor (PDGF)-AB, IL-12p70, IL-21, and PDGF-BB] and a significant negative correlation with 1 anti-inflammatory cytokine [bone morphogenetic protein 7 (BMP-7)]. IL-8, CCL-3, serpin E1, PDGF-AB, and IL-1β were significantly upregulated in the orbital adipose tissue of TRAb-positive patients compared to TRAb-negative patients. In contrast, BMP-7 demonstrated an opposite trend. Additionally, TRAb and CAS significantly decreased following IVMP therapy, with a significant correlation between the extent of reduction in TRAb and CAS.

Conclusion: TRAb significantly correlated with both CAS (clinical inflammation indicator) and inflammatory cytokines (pathological inflammation marker). Consequently, we propose, for the first time, that TRAb may serve as an objective and quantitative biomarker for assessing inflammation in TED.

Context: Dyslipidemia adversely affects female fertility; however, its relation with recurrent pregnancy loss (RPL) and its underlying mechanisms remains unclear.

Objective: This study aims to analyze the impact of dyslipidemia on natural killer (NK) cell cytotoxicities and autoimmunity in women with RPL and to elucidate how lipids affect cellular immunity.

Design: A retrospective cross-sectional study with ex vivo experiments.

Setting: University clinic.

Patients: One hundred fifteen RPL women, including 70 nondyslipidemia and 45 dyslipidemia women.

Interventions: Dyslipidemia.

Main outcome measures: Cellular immune activity and autoimmune parameters were evaluated.

Results: Out of 115 women, 45 (39.1%) had dyslipidemia. The prevalence of anti-single-stranded and anti-thyroglobulin antibodies was significantly higher in dyslipidemia women. NK cell cytotoxicity, measured at effector to target cell ratio (E:T) of 25:1 and 12.5:1, was significantly higher in women with dyslipidemia (P < .05). NK cell cytotoxicities (E:Ts of 25:1 and 12.5:1) were positively correlated with serum total cholesterol and low-density lipoprotein cholesterol levels (all P < .05). However, there were no differences in the T helper 1 (Th1)/Th2 cytokine-producing cell ratios between the two groups. The ex vivo study revealed that pretreatment with oxidized low density lipoprotein (oxLDL) enhanced the conjugation of NK cells with target cells and increased perforin secretion. NK cell cytotoxicities were significantly increased after pretreatment with 5 and 50 μg/mL oxLDL (P < .05 each).

Conclusion: A significant proportion of women with RPL have dyslipidemia, and the risk of autoimmune and cellular immune abnormalities is increased in women with a history of RPL and dyslipidemia.

Context: Relationship between obesity and the sense of taste is complex, with many inconsistent and conflicting findings that are largely methodology dependent. The impact of glucagon-like peptide-1 analogues on taste remains largely unaddressed.

Methods: In this 16-week, single-blinded, placebo-controlled study, 30 women with polycystic ovary syndrome (PCOS), aged 33.7 ± 6.1 years with a body mass index of 36.4 ± 4.4 kg/m2 were randomized to semaglutide 1.0 mg once weekly or placebo. Change in taste recognition was assessed by 16 strips impregnated with 4 different concentrations of the 4 basic tastes. Tongue biopsies were performed for gene expression analysis. Brain responses to visual cues of sweet and savory foods and to sweet solution dripping on the tongue were evaluated by functional magnetic resonance imaging.

Results: Semaglutide improved overall taste recognition score from 11.9 ± 1.9 points to 14.4 ± 1.0 points, with an estimated treatment difference of 2.5 points (95% CI, 1.7-3.3). The genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste signaling transduction pathways, neural plasticity, and renewal of taste buds, showed differential RNA expression by a multi-tiered analytical pipeline. Semaglutide decreased activation of putamen in response to visual food cues and increased activity in the angular gyrus of the parietal cortex in response to sweet solution after meal intake (semaglutide vs placebo, P < .001).

Conclusion: In women with obesity and PCOS, semaglutide improved an overall taste recognition score, altered RNA expression in the tongue and modified brain activity in response to sweet and savory food cues and to tasting sweet solution.