Journal of Endocrinological Investigation最新文献

Objectives: The relationship between the patterns of WC trajectory and fragility fracture in the Chinese population remains unclear. This prospective study investigated the effect of long-term WC trajectory on fragility fracture based on community-based cohort.

Methods: This prospective study was conducted based on the Kailuan Study and included a total of 47,288 participants (mean age, 56.7 years) free of fragility fracture and with repeated measurements of WC from 2006 to 2014. The WC trajectories (2006-2014) were modeled by group-based trajectory modeling (GBTM), and three trajectories were identified: low-stable group (n = 12,546), medium-stable group (n = 28,532), and high-stable group (n = 6,210). The association between WC trajectories and incident fragility fractures was assessed using Cox proportional hazards models, with stratified analyses and interaction tests conducted by sex (male/female) and age (≤ 65 years / > 65 years).

Results: During an average follow-up of 8.31 years, 663 participants developed fragility fractures. After adjusting for potential confounding factors, compared with those in the low-stable group, the hazard ratio (HR) and 95% confidence interval (CI) for incident fragility fracture in the medium-stable group and high-stable group were 1.25 (1.01-1.54) and 1.55 (1.12-2.14), respectively. In Individuals aged ≤ 65 years, the medium group and high-stable group had a 35% (HR = 1.35, 95% CI: 1.03-1.77) and 98% (HR = 1.98, 95% CI: 1.32-2.97) higher fracture risk, respectively.

Conclusions: WC trajectories were significantly associated with the risk of fragility fracture, and the association was more evident in aged ≤ 65 years population.

Purpose: Aging is accompanied by a chronic low-grade systemic inflammatory state known as "inflammaging", driven by the accumulation of pro-inflammatory and immunosenescent cells, oxidative stress, and dysregulation of apoptosis and autophagy. Experimental evidence suggests that caloric restriction (CR) can slow down inflammaging, although its impact on spermatogenesis remains controversial. This study aimed to investigate the effects of CR on age-related testicular inflammation and any effects on germ cells.

Methods: Fourteen 18-month-old Sprague-Dawley rats were randomly divided into two groups and sacrificed after 6 months: 7 rats on a normal ad libitum diet (ND) and 7 rats on CR (40% reduction in caloric intake). Western blot (WB) and immunohistochemical (IHC) analyses were performed to assess the expression of key markers of inflammation, oxidative stress, apoptosis, and autophagy, alongside morphological evaluations.

Results: IHC analysis reveals that CR disrupts germinative epithelium and somatic cells, and reduces the expression of Ob-R, GLP-1R, GPX4, NOX4, and SIRT1. WB analysis showed that CR lowered COX2 expression, through downregulation of the NFκB/MAPK pathway, decreased the expression of NLRP3 inflammasome, Caspase-1, and pro-inflammatory cytokine IL1-β, and restored redox homeostasis. Consistently, IHC highlighted a marked reduction in proinflammatory immune cell infiltration in the testis of CR rats. Moreover, as a consequence of the germ cells number reduction CR-induced, we observed a decreased expression of p75NTR and its pro-apoptotic signaling components (pJNK, p53, and BAX), while concurrently downregulating p62/SQSTM1 expression.

Conclusions: Our findings highlight the dual impact of CR on testicular aging, on the one hand the significant attenuation of oxi-inflammation, on the other hand the impairment of germinal epithelial physiology. These results underscore the need for further studies to define optimal timing and duration of dietary interventions aimed at mitigating age-related decline in male reproductive function.

Purpose: Bilateral inferior petrosal sinus sampling (BIPSS) is considered the most accurate procedure to confirm the diagnosis of Cushing's disease (CD). However, it is a cumbersome and costly procedure. We aim to determine whether the corticotropin-releasing hormone (CRH) test alone might differentiate CD from ectopic adrenocorticotropin (ACTH) syndrome (EAS).

Methods: In this retrospective, observational study we investigated 523 consecutive patients with ACTH-dependent hypercortisolism: 502 with CD and 21 with EAS. All patients underwent a CRH test and surgery for the removal of the ACTH-secreting tumor. Two hundred patients with CD and 17 with EAS underwent BIPSS. The diagnostic CRH test performance included sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR).

Results: using a 50% ACTH increase as the threshold, the CRH test correctly classified 438 cases of CD (87%) and 20 cases of EAS (95%). The diagnostic metrics were as follows: SE 87%, SP 95%, PPV 99%, NPV 23%, accuracy 92%, PLR 18.35, and NLR 0.05. BIPSS correctly diagnosed all cases of EAS (100%) and 188 cases of CD (94%).

Conclusions: Our study shows that a positive CRH test reliably differentiates CD from EAS and obviates the need for BIPSS. The performance of CRH test is similar in patients with and without a visible pituitary microadenoma or a microadenoma < 6 mm. Accepting the very low probability of EAS in a patient with positive ACTH response to CRH, we can propose pituitary surgery without performing BIPSS.