Endocrine最新文献

Objective: Patients with distant metastatic medullary thyroid carcinoma (DMMTC) often undergo primary tumor resection (PTR) with or without neck lymph node dissection (NLND) before systemic therapy. However, whether these patients benefit from treatment remains unclear.

Methods: Patients with DMMTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020. The overall survival (OS) and disease-specific survival (DSS) were established by Kaplan-Meier curves and were compared using the log-rank test or two-stage test between different treatment modalities (surgery, non-surgery) after propensity score matching (PSM). We also analyzed the effects of surgical and non-surgical treatments on the OS and DSS of patients stratified by TNM stages T1-2 and T3-4 in this cohort.

Results: Among the 2336 patients with medullary thyroid carcinoma from the SEER database, 186 were diagnosed with DMMTC, with an average follow-up period of 28.12 months. Pairwise analysis after PSM revealed that the surgery group had a significantly improved survival rate compared to the non-surgery group (OS p = 0.00039, DSS p = 0.001). The survival advantages of the above-mentioned surgery group were maintained when stratified by stages T1-2 and T3-4.

Conclusion: Our results demonstrate that PTR with or without NLND, as an initial therapy, can benefit the survival rate of patients with DMMTC.

Objective: The existing evidence regarding the impact of tamoxifen on lipoprotein(a) and apolipoproteins remains inconsistent. Therefore, this updated meta-analysis of randomized controlled trials (RCTs) aims to enhance the quality of evidence concerning the effects of tamoxifen on these lipid parameters.

Methods: Eligible RCTs published up to October 2024 were meticulously selected through a comprehensive search. A meta-analysis was then performed using a random-effects model, and results were presented as the weighted mean difference (WMD) with a 95% confidence interval (CI).

Results: Findings from the random-effects model revealed an increase in ApoA-I (WMD: 15.22 mg/dL, 95% CI: 6.43-24.01, P = 0.001), alongside decreases in ApoB (WMD: -9.33 mg/dL, 95% CI: -15.46 to -3.19, P = 0.003) and lipoprotein(a) (WMD: -3.35 mg/dL, 95% CI: -5.78 to -0.91, P = 0.007) levels following tamoxifen treatment in women. Subgroup analyses indicated a more significant reduction in lipoprotein(a) levels in RCTs with a duration of ≤24 weeks (WMD: -3.65 mg/dL) and in studies using tamoxifen doses of ≥20 mg/day (WMD: -4.53 mg/dL).

Conclusion: This meta-analysis provides evidence that tamoxifen leads to a decrease in lipoprotein(a) levels, along with reductions in ApoB and increases in ApoA-I among women.

Purpose: To compare ovarian function measures in euthyroid women with normogonadotropic anovulation in subclinical hypothyroidism (SCH) or thyroid autoimmunity (TAI) to those without thyroid dysfunction.

Design: A prospective open-label cohort study analyzed anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone, estradiol and testosterone concentrations, ovarian volume, and polycystic ovarian morphology (PCOM) incidence between women with and without SCH or TAI in two study arms: polycystic ovary syndrome (PCOS) and hypothalamic-pituitary-ovarian dysfunction (HPOD).

Results: The prevalence of circulating thyroid peroxidase antibodies (TPOAb) was higher in the PCOS compared to the HPOD arm (p = 0.006). No significant differences in the measured parameters were observed based on SCH or TAI status across the entire cohort or individual study arms, except for phenotype D of PCOS, where a greater volume (p = 0.031) and higher incidence of physiological lesions (p = 0.047) in the left ovary were noted in SCH, and phenotype A, where LH concentrations (p = 0.038) were significantly higher in women without TAI. In the PCOS arm, thyroglobulin antibodies (TGAb) concentration correlated negatively with FSH (p = 0.049) and positively with testosterone (p = 0.012) concentrations, while in the HPOD arm, TPOAb and FSH concentrations were negatively correlated (p = 0.028).

Conclusions: No clinically significant impact of SCH on ovarian function measures was demonstrated. Regarding TAI, significant correlations with still uncertain clinical significance were observed with FSH concentrations, both in PCOS and in HPOD. In view of the obtained results, the benefits of thyroxine supplementation to address menstrual irregularities and improve obstetric outcomes in the examined conditions, require support with clinical evidence.

Purpose: To evaluate the diagnostic value of different subtypes of non-punctate echogenic foci in thyroid malignancy.

Methods: Retrospective research of 342 thyroid nodules with calcification was performed. The echogenic foci were divided into punctate echogenic foci (type I) and non-punctate echogenic foci (type II), and type II were further divided into four subtypes: macrocalcification (type IIa), continuous peripheral calcification (type IIb), discontinuous peripheral calcification (type IIc) and isolated calcification (type IId). Postoperative histopathological results were used as the gold standard to evaluate the correlation between non-punctate echogenic foci subtypes and thyroid malignancy.

Results: The malignant risk of nodules with echogenic foci was type I (82.1%) > type IIa (66.2%) > type IIc (52.9%) > type IId (16.7%) > type IIb (13.9%), P < 0.001. Type I and type IIa echogenic foci were independent risk factors for thyroid cancer (OR = 16.593, 7.785). Solid, hypoechogenicity/marked hypoechogenicity and a single lesion in a unilateral thyroid lobe were independently associated with malignant thyroid nodules with macrocalcification(OR = 6.825, 40.042, 5.201). Irregular margins and uneven calcification thickness were independent factors for malignant thyroid nodules with peripheral calcification (OR = 5.676, 2.750).

Conclusion: Type IIa echogenic foci could independently predict thyroid malignancy. The diagnostic value of non-punctate echogenic foci depended on the differentiated combination of ultrasound characteristics. Type IIa nodules with solid composition, irregular margins, and a single lesion in a unilateral thyroid lobe implied a higher risk of malignancy; peripheral calcified nodules with irregular margins and uneven calcification thickness suggested an increased risk of malignancy.

Purpose: We aimed to characterize the RYGB-induced changes in the dynamics of brain glucose uptake. We addressed heterogeneity between brain regions during experimental normo- and hypoglycemia and explored associations with anthropometric and metabolic outcomes of RYGB.

Methods: Analyses of regional brain glucose uptake were performed on 9 individuals with obesity and no diabetes, investigated with combined brain ¹⁸F-FDG-PET and fMRI during hyperinsulinemic normo- and hypoglycemic clamp, one month before and four months after RYGB. FDG clearance, reflecting glucose uptake rate, was assessed in 38 brain regions, covering all cortical areas and subcortical nuclei, during hyperinsulinemic normo- and hypoglycemia. Correlation analyses were performed to identify associations with other outcomes of RYGB.

Results: FDG uptake rate during hypoglycemia was higher than during normoglycemia in all brain regions, both before and after RYGB. Moreover, in most regions and especially in cortical areas involved in inhibitory behavioral control, FDG uptake rate tended to be reduced after surgery during normoglycemia but elevated during hypoglycemia. However, these post-surgical changes in FDG uptake rate were opposite in the hypothalamus. Thus, the hypo-to-normoglycemia FDG clearance ratio tended to increase in all brain regions following RYGB, but not in the amygdala and the hypothalamus. Changes in regional FDG uptake rate after RYGB during normoglycemia were associated with weight loss and improved systemic insulin sensitivity.

Conclusion: Using dynamic FDG-PET, we show region-specific patterns of changes in glucose utilization following RYGB. In the hypothalamus, glucose uptake during normoglycemia tended to rise after RYGB while it was reduced in cortical regions involved in behavioral control. Following RYGB, the hypothalamus and amygdala, in contrast to other regions, displayed trends of reduced glucose uptake during hypoglycemia. These pilot results highlight the brain effects of RYGB and suggest behavioral and neuroendocrine adaptations which contribute to its antidiabetic effects.

Purpose: Congenital isolated adrenocorticotropic hormone deficiency (CIAD) is an autosomal recessive disorder. This study identifies novel TBX19 variants for CIAD patients, explores its possible effect mechanism at the structural, functional and protein levels, and guides clinicians better understand the condition.

Methods: The clinical characteristics of three CIAD children were summarized. Multiple sequence alignment was performed and five algorithms, PROVEA, PolyPhen2, Mutation Taster, FATHMM, and I Mutant2.0, were used for the pathogenicity prediction. In addition, the three-dimensional protein structure of wild-type TBX19 was generated by Alphafold 3 and its variants were shown using PyMOL. Furthermore, immunoblotting analysis was applied to examine changes in the protein levels and the luciferase reporter assay was performed to further investigate the effects of TBX19 and its variants on pro-opiomelanocortin (POMC) transcriptional activity.

Results: We describe three Chinese patients with CIAD caused by TBX19 variants. The TBX19 variant, c.856C>T (p.R286*) was classified as pathogenic according to ACMG, whereas the other four variants, c.377C>T (p.P126L), c.602A>T (p.E201V), c.401A>G (p.H134R) and c.299G>A (p.R100H) were predicted to be disease-causing. Variants lead to alter interactions, conformational changes in proteins or truncate protein. TBX19 and PITX1 cooperated, resulting in a strong synergistic activation effect on POMC transcriptional expression. A functional study showed that the variants in our study result in a significant suppression of POMC transcriptional activity compared to wild-type TBX19.

Conclusions: Our study identifies five TBX19 loss-of-function variants, two of which are novel and that provides new perspectives into the pathophysiological mechanism and expands the variant spectrum in IAD.

Regulatory molecules typically work cooperatively to ensure the efficient functioning of hormonal systems. Examples include LH and FSH in reproductive biology, insulin and glucagon in glucose metabolism. Similarly, calcium and phosphorus are important regulators of skeletal homeostasis. In the circulation, these molecules are under the control of PTH, 1,25(OHD), and FGF23. In turn, these hormones depend upon a mutual and complex interplay among themselves. For example, alterations in calcium metabolism influence phosphorus homeostasis, as occurs in primary hyperparathyroidism (PHPT). Not as well recognized is the influence that abnormalities in phosphorus metabolism can have on calcium homeostasis. In this review, we call attention to the impact that abnormalities in phosphorus can have on calcium metabolism.

Purpose: This study aimed to determine the detection rate of autoimmune polyendocrine syndrome (APS) among children with Graves' disease (GD) at a single center and to compare clinical characteristics between those with isolated GD and those GD with APS (APS-GD).

Methods: A retrospective analysis was conducted on the clinical data of 555 patients and were categorized into isolated GD and APS-GD groups based on their progression status. The time for FT₄ to return to normal was used as an indicator of short-term treatment effectiveness.

Results: In all, 63 (11.4%) had coexisting APS; 52 (82.5%) were female. The most common component of APS was type 1 diabetes mellitus (T1DM) [24 (4.3%)]. Among APS-GD patients, after the diagnosis of the first component, the cumulative incidences of a second disease within the first, second, and third years were 63.4%, 74.6%, and 82.0%, respectively and till the end of the first decade reached 95.0%. The isolated GD group had higher levels of FT₃, TT₃, and TRAb. Under the same initial dosage, the median time for FT₄ to normalize was 22.0 (14.0, 30.0) d for the isolated GD group and 25.0 (13.5, 31.0) d for the APS group (P = 0.936).

Conclusion: The study uncovered a high comorbidity rate of APS in children with GD, suggesting that patients with APS-GD have a higher risk of progression to additional endocrine gland disorders. Yet, both groups showed no significant difference in their short-term therapeutic response. These findings are crucial for guiding the clinical management and follow-up of pediatric GD patients.

Objectives: With the prolongation of life expectancy in patients with myasthenia gravis, the number of comorbidities is increasing. Diabetes mellitus is one of the main comorbidities faced by patients with myasthenia gravis. However, there is not enough epidemiological information on diabetes mellitus. Given these limitations, the purpose of this study was to review the prevalence of diabetes mellitus in patients with myasthenia gravis and whether the myasthenia gravis is associated with an increased risk of gestational diabetes mellitus.

Methods: PubMed, Embase, and Web of Science were searched for articles published prior to February 2024. Endnote 21 software was used to manage all relevant records. Review Manager version 5.4 and Stata version 18.0 software were used for the statistical analysis. Funnel plots and Egger's test were used to assess publication bias.

Results: Twenty-four articles met the inclusion criteria and were included in the study. Among 23,516 myasthenia gravis patients, the prevalence of diabetes mellitus was 17% (95% CI 12~22%). In addition, the meta-analysis of the two studies showed that myasthenia gravis was significantly associated with an increased risk of gestational diabetes mellitus (OR = 1.56, 95% CI 1.26~1.93, p < 0.01).

Conclusions: Among the comorbidities of myasthenia gravis patients, diabetes mellitus is common, and the risk of gestational diabetes mellitus is increased in myasthenia gravis patients. These findings remind us that diabetes mellitus seems to be an important issue in the clinical management of myasthenia gravis patients and requires more attention.

Purpose: This study aims to evaluate the association between psychiatric disorders and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) treated at a tertiary care hospital.

Methods: A propensity score-matched case-control study was conducted, comprising a total sample of 194 participants (97 DKA cases and 97 controls without DKA). Comprehensive data were collected on clinical, anthropometric, and socioeconomic characteristics, and psychiatric disorders were classified according to international standards.

Results: The mean age of the participants was 47.4 ± 17.7 years, with 55.6% being female. Psychiatric disorders were identified in 16.5% of the study population. The prevalence of psychiatric disorders was significantly higher in DKA cases compared to controls (24.7% vs. 7.2%, p < 0.001). Conditional logistic regression models revealed that the association between psychiatric disorders and DKA was not independent of HbA1c levels. Additionally, in HbA1c-stratified analyses, patients with psychiatric disorders developed DKA at lower HbA1c levels compared to controls.

Conclusion: Psychiatric disorders significantly increase the risk of DKA in adults with T1D, particularly among those with less elevated HbA1c levels. These findings highlight the critical importance of addresing psychiatric comorbidities in the management of T1D, given the severe implications and significant healthcare resource utilization associated with DKA.