Journal of Endocrinological Investigation最新文献

Introduction: The prevalence of secondary hypertension is reported to be 5-15% of people with hypertension. Causes of secondary hypertension include Cushing's syndrome (CS), a rare but serious clinical condition characterized by chronic endogenous hypercortisolism associated with increased morbidity and mortality, especially for cardiovascular complications. The challenge for the clinician is thus to identify the phenotype of hypertensive patients who should be screened for endogenous hypercortisolism.

Methods: This study was performed according to the PRISMA statement. The search was last updated in June 2023, and only English language studies were considered. Titles and abstracts have been screened for articles selection, identifying only those that dealt with prevalence of Cushing's syndrome in hypertensive patients. Finally, eight papers were included in the review. Data regarding year of publication, populations' characteristics, inclusion criteria, screening test and cut-off used, and CS prevalence have been extracted.

Results: The study search identified eight studies, from 1977 to 2020, including a total number of 11,504 patients, ranging from 80 to 4429 patients for each study. The prevalence of CS reported was variable among the studies, ranging from 0 to 7.7%, having Cushing's disease (CD) a prevalence range of 0-1.2%. The highest prevalence has been found in selected populations of hypertensive patients younger than 40 years (6.2%) or harbouring an adrenal lesion (7.7%). The most used screening test was 1 mg overnight dexamethasone suppression test (1 mg DST), with different cut-off.

Conclusion: The most fitting CS profile encompasses younger age (i.e., < 40 years old), rapidly evolving hypertension and the presence of adrenal adenomas, along with subjects with pituitary lesions, who should still be prioritized in the diagnostic pathway. Overall, in the case of hypertensive patients presenting a clinical picture highly suggestive of CS, it is advisable to perform one of the available screening tests (UFC, 1 mg DST, LNSC). LNSC is likely the most discriminatory test and may be preferred, depending on its availability. Conversely, for hypertensive patients with an adrenal incidentaloma, the 1 mg DST is recommended as the screening test to exclude CS.

Purpose: Graves' orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients' lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO.

Methods: This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho).

Results: HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels.

Conclusions: Alterations in patients' lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO.

Purpose: To compare the feasibility and safety of three approaches for bilateral adrenal venous sampling (AVS) and their influence on the outcomes of adrenalectomy for dominant lateral primary aldosteronism (PA).

Methods: 182 PA patients who underwent AVS at Fuwai Hospital between January 2022 and March 2024 were enrolled. According to the puncture access, patients were divided into three groups: simultaneous AVS via antecubital approach group (Group A, N = 48), simultaneous AVS via femoral approach group (Group B, N = 44) and sequential AVS via antecubital approach group (Group C, N = 90). The baseline data, procedure parameters, success rates, complication rates and follow-up data were analyzed.

Results: The baseline characteristics did not differ significantly among three groups (all P > 0.05). The procedure time (18.9 ± 7.4 min vs. 25.2 ± 7.5 min; P < 0.001) and fluoroscopy time (7.1 ± 3.8 min vs. 10.8 ± 6.2 min; P < 0.001) were shorter in Group A than in Group C. However, there was no significant difference between Group A and B (all P > 0.05). The bilateral sampling success rates in Groups A, B and C were 93.8%, 93.2% and 91.1%, respectively, which were not significantly different (P = 0.936). One (0.5%) adrenal haematoma was recorded in Group B. The complete clinical success rate (P = 0.894) and complete biochemical success rate (P = 0.954) were not significantly different in patients with dominant lateralization who underwent adrenalectomy.

Conclusion: This study revealed that three approaches for AVS are safe and feasible, with similar outcomes after adrenalectomy. Simultaneous AVS via antecubital approach might be a better choice considering its shorter procedure and fluoroscopy time and comfort.

Purpose: Traumatic Brain Injury (TBI) poses a significant global health burden, with Mild TBI (mTBI) being the most prevalent form. TBI triggers activation of the hypothalamic-pituitary-adrenal (HPA) axis, which in turn affects the hypothalamic-pituitary-gonadal (HPG) axis regulating oogenesis and spermatogenesis. In this study, we investigated the impact of mTBI on sperm genome integrity using a repetitive mTBI (r-mTBI) mouse model.

Methods: We assessed sperm telomere length (TL), free TERRA (fTERRA), and DNA/RNA hybrid TERRA (hTERRA) levels, alongside transcriptional changes in genes involved in TERRA regulation and DNA damage response.

Results: Our findings reveal that a single mTBI event leads to a significant reduction in sperm TL during the acute phase, followed by an increase in TL during the chronic phase of r-mTBI, reminiscent of aging-associated changes. Moreover, we observed alterations in the transcription levels of Rad51, Exo1, Rb1, RNaseH1, and RNaseH2 genes, particularly in association with fTERRA and hTERRA levels, following mTBI.

Conclusion: Understanding the potential non-Mendelian effects of TBI holds promise for elucidating TBI pathogenesis, mechanisms of TBI-induced diseases, and conditions of unknown etiology. Given the risks associated with repeated TBI exposure, especially in sports like football and boxing, consideration of potential paternal transmission of effects to offspring is crucial.

Purpose: Irisin, an adipokine closely correlated with metabolism, may affect adults' executive function (EF). But little is known about this association in school-aged children, particularly regarding differences across weight status (i.e., thinness, normal-weight, overweight/obesity). Therefore, we aimed to examine the associations of irisin with EFs in school-aged children, and further explore whether weight status modifies these correlations.

Methods: Children aged 7-12 years were recruited from five schools in 2017 in Guangzhou, China. Plasma irisin levels were assessed using an enzyme-linked immunosorbent assay. EFs were assessed using the Stroop Color-Word test (inhibitory control), Corsi Block-Tapping task (working memory), and Wisconsin Card Sorting test (cognitive flexibility). Children's weight status was objectively measured and classified into three groups. Multivariable linear regression was performed, with stratified analysis by weight status.

Results: A total of 502 children were included. In the overall sample, no significant associations between irisin and EFs in children were found. However, higher irisin levels were significantly associated with better Stroop Color-Word test performance among children with overweight/obesity (response time: β = -0.129, 95%CI: -0.228, -0.030; word interference time: β = -0.088, 95%CI: -0.163, -0.013). Null significant associations in the groups with thinness or normal-weight were found. Weight status significantly modified the associations of irisin with EFs (P_interaction<0.05).

Conclusions: Children with overweight/obesity might be more sensitive to the effect of irisin on EFs, especially on inhibitory control. Irisin might be a promising target to promote EF development in overweight/obese children.

Background: Subclinical hypothyroidism (SCH) is closely associated with heart failure and cardiac hypertrophy, yet the underlying mechanism remains unclear.

Methods: Cardiomyocytes treated with thyroid-stimulating hormone (TSH) were used as an in vitro model. Cardiac-specific TSHR knockout mice (CKO) were treated with isoproterenol (ISO) to induce cardiac hypertrophy in vivo. Serum FT4, TSH levels, heart weight, body weight and tibial length of mice were evaluated. Heart function was analyzed by M-mode cardiac ultrasonography. The pathological changes in cardiac tissues were detected by immunohistochemistry, hematoxylin-eosin and WGA staining. mRNA levels of ANP, BNP, α-MHC and β-MHC were evaluated by RT-PCR. Western blot was used to detect pathway related proteins. Besides, the transcriptome sequencing analysis and dual-luciferase reporter assays were used to verify the relevant molecular mechanisms.

Results: TSH significantly promotes cardiomyocyte hypertrophy in cardiomyocytes. Meanwhile, cardiac-specific TSHR knockout significantly reduced ISO-induced cardiac hypertrophy. This was demonstrated by reductions in cell sizes, decreased HW/BW and HW/TL ratios, along with improved expression of hypertrophic genes. Further transcriptome sequencing results showed that TSH can significantly promote the expression of CYP4B1 in vitro. And the knockdown of CYP4B1 repressed TSH-induced cardiomyocyte hypertrophy. Further mechanistic studies revealed that TSH regulated the expression of CYP4B1 hypertrophy through the PI3K/AKT/CREB signaling pathway. Subsequently, the dual-luciferase assays demonstrated that CREB promotes the transcription of CYP4B1 by binding to its promoter region.

Conclusion: Overall, our findings highlight the direct impact of TSH/TSHR on cardiomyocyte hypertrophy and proposed CYP4B1 as a promising target for mitigating cardiac hypertrophy in SCH patients.

Context: Macroprolactinomas not only cause hypogonadism, but also other pituitary dysfunctions, like deficiency of adrenocorticotrophic hormone (ACTH) and thyroid-stimulating hormone (TSH). While dopamine agonist treatment shows varying recovery rates of these insufficiencies, surgical outcomes are less studied, and a direct comparison between treatments is lacking.

Objective: To evaluate recovery of pituitary dysfunction in medically vs. surgically treated patients with macroprolactinoma.

Design: Retrospective multicenter study including 104 patients with macroprolactinoma (44 surgically vs. 60 medically treated) with at least two hormonal deficiencies before treatment.

Results: Before surgery, all patients presented with hypogonadotropic hypogonadism, 25 (57%) with ACTH-deficiency, and 32 (73%) with TSH-deficiency. 10 months post-surgery, prolactin normalized in 25 (57%) patients, while 19(43%), 15 (60%) and 10(31%) recovered from hypogonadism, ACTH-deficiency, and TSH-deficiency, respectively. Before medical therapy, hypogonadism was observed in all patients, ACTH-deficiency in 31 (52%), and TSH-deficiency in 50 (83%). After 12 months under dopamine agonists, prolactin levels normalized in 36 (60%) patients, 25(42%) recovered from hypogonadism, 17 (55%) from ACTH-deficiency, and 14(28%) from TSH-deficiency. No significant difference in recovery rates between surgical and medical treatment for hypogonadism (OR 1.633, p = 0.338), ACTH-deficiency (OR 0.462, p = 0.319), or TSH-deficiency (OR 0.584, p = 0.339) was observed. Large initial tumor size was a significant negative predictor of recovery for all hormone deficiencies (always p < 0.05), while prolactin normalization was a predictor of recovery of hypogonadism (p < 0.001).

Conclusion: Both surgical and medical treatment allow for hormonal recovery in patients with macroprolactinoma, with no significant advantage for either approach. Initial tumor size and prolactin-normalization are predictors of recovery outcomes.

Purpose: To identify distinct Th-like regulatory T cell (Treg) subsets in the peripheral blood of individuals with type 1 diabetes (T1D) and investigate potential factors that affect Treg polarization within the context of autoimmunity.

Methods: A total of 49 T1D patients and 20 healthy controls (HCs) were enrolled in this study. Th-like Treg subsets, including Th1-like, Th2-like and Th17-like Tregs, as well as Th cell subsets in peripheral blood were assessed by flow cytometry. Single nucleotide polymorphisms in Treg-related genes were analyzed. The levels of inflammatory cytokines were measured by ELISA.

Results: We observed a decreased frequency of Th1-like Tregs in peripheral blood of T1D patients, while the proportion of total Foxp3⁺ Tregs remained unchanged. Moreover, an imbalance of Th17-like Treg/Th17 cells was noted, characterized by a decreased frequency of Th17-like Tregs and an increased proportion of Th17 cells. Further analysis revealed a correlation between the frequency of Th2-like Tregs and the risk variants of IL-2RA rs3118470. Notably, T1D patients with a normal weight exhibited a higher frequency of Th1-like Tregs compared to their lean and overweight counterparts. However, Treg plasticity was not associated with disease characteristics. Additionally, the serum levels of IL-1β, TNF-α and IL-6 in T1D patients were significantly higher than those in HCs, and the proportions of Th1-like and Th2-like Tregs were negatively associated with IL-6 and TNF-α concentrations in T1D patients, respectively. Nevertheless, the proportions of Th-like Treg subsets in the peripheral blood of HCs exhibited no significant correlation with age, BMI, or the levels of inflammatory cytokines.

Conclusion: Our study has provided novel evidence on the altered plasticity and the possible mechanisms underlying the transformation of conventional Tregs towards Th1-like and Th17-like Tregs in the peripheral blood of T1D patients. The findings serve to further augment our understanding of the Treg-mediated immune imbalance that plays a crucial role in the immunopathogenesis of T1D.