Endocrine最新文献

Purpose: One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity.

Methods: Patients with BMI ≥ 30 kg/m² and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels.

Results: Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage.

Conclusion: The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health.

Purpose: New drugs are needed for the therapy of anaplastic thyroid cancer (ATC). This study aims to investigate doxorubizen (a dual-action structural hybrid (chimera) of doxorubicin (Dox) and DNA methylating drug temozolomide), in comparison with Dox, and alone or in combination with lenvatinib in ATC 8305C cells, and in primary human ATC cell cultures (pATC).

Methods: We have investigated doxorubizen, Dox, and lenvatinib on 5 different pATC and in continuous 8305C cell line in vitro, evaluating their effect on cells proliferation by WST-1, apoptosis (Hoechst ad Annexin V assays) and migration (Chemicon QCM™ 96-well Migration Assay).

Results: The results have demonstrated: (1) a significant antiproliferative and proapoptotic effect of doxorubizen in 8305C and in pATC; (2) a significant antiproliferative and proapoptotic effect of Dox in pATC, and in 8305C; (3) the antineoplastic effect of lenvatinib in 8305C and in pATC; (4) a stronger antiproliferative and proapoptotic effect of doxorubizen than that of Dox, or lenvatinib; (5) that doxorubizen induced an inhibition of migration in pATC stronger than that of Dox, or lenvatinib; (6) that doxorubizen is able to synergize in vitro with lenvatinib increasing the antiproliferative effect, while doxorubizen alone is the primary factor that promotes the proapoptotic impact.

Conclusion: We have first shown that doxorubizen has a potent antineoplastic effect in vitro in 8305C and in 5 different pATC, and that can synergize with lenvatinib. These results open the way to a future evaluation of the antineoplastic effect of doxorubizen in ATC patients.

Purpose: Parathyroid carcinoma (PC) is a rare malignancy with a poor prognosis. Diagnosis of PC is often difficult in clinical practice and efficient diagnostic markers are still needed for differential diagnosis. Aberrant glycosylations of glycoproteins were identified with lectin microarray in various cancers, while relevant information is lacking in PC.

Methods: In this study, 8 PC and 6 parathyroid adenoma (PA) tissues were assessed using a microarray consisting of 70 lectins. Overall lectin-specific glycosylation patterns were compared between PA and PC tissues. Lectins with significant differential response between PC and PA were further validated by lectin histochemistry.

Results: The difference in signal intensities was found in 71.4% (50/70) of the lectins between the two groups (P < 0.05). The vast majority of PCs had higher intensity signals than PAs (PCs vs. PAs, ratio >1) and amaranthus caudatus (ACL) showed the most significantly different response between them (ratio = 2.45). Lectin histochemistry further confirmed higher ACL intensity in PCs than in PAs. The differentially expressed glycans in PC tissues were primarily glucose, mannose, and galactose-based.

Conclusion: PC presented unique glycomic features and ACL may serve as a candidate diagnostic marker for PC.

Background: Hyperaldosteronism is an endocrine disorder leading to persistent and severe hypertension. G protein-coupled estrogen receptor 1(GPER1) is regarded as a potential receptor of aldosterone (ALDO).

Objective: This study aimed to investigate the effects of GPER1 on aldosterone (ALDO)-induced hypertension and inflammation in mice.

Methods: GPER1-knockout (KO) and wild-type (WT) C57BL/6j mice were divided into control (CON, normal saline treatment), ALDO (subcutaneous injections of 600 g/kg/d ALDO), and ALDO + eplerenone (EPL) (subcutaneous injections of 600 g/kg/d ALDO and 100 mg/kg/d EPL) groups (n = 5 per group). Fourteen days after drug administration, the heart rate and tail blood pressure of the mice in the different groups were measured. S100A8 and IL-1β protein expression in arterial tissues were detected by western blotting, NLRP3 expression was assessed using immunofluorescence, and CD68 expression was investigated using immunohistochemistry.

Results: GPER1 deficiency alleviated ALDO-induced diastolic blood pressure (P< 0.05). In addition, the protein expression levels of IL-1β, S100A8, and CD68 showed significant decreases in the arterial tissues of GPER1-KO mice after combination treatment with ALDO and EPL (all P < 0.05).

Conclusion: We discovered attenuation of hypertension and vascular inflammation of GPER1 KO mice only on the basis of mineralocorticoid receptor (MR) blocking. Collectively, our study indicates that GPER1 might become a therapeutic target of hyperaldosteronism in controlling the residual risk of cardiovascular disease when MR antagonist alone is not satisfying.

Purpose: To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature.

Methods: Whole exome sequencing (WES) was performed and a literature review was conducted.

Results: Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type II were included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P < 0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P < 0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P < 0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P = 0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. In patients with IGHD type I harboring gross deletion, an early age of diagnosis correlated with both a higher height SDS at diagnosis and a better response after GH treatment. Height SDS after GH treatment in patients with IGHD type II carrying splicing mutations was negatively correlated with age at diagnosis.

Conclusion: We identified two GH1 gene mutations, c.316delC (p.L106Cfs*35) and deletions of exon 1-5 in four Chinese patients with IGHD type I. They had a good response to GH treatment and gained satisfactory height improvement. Early diagnosis and initiating treatment may lead to a better prognosis.

Introduction: Acromegaly is associated with a possible increased risk of neoplasias, like colorectal cancer (CRC), although magnitude of this risk is unclear.

Objectives: Evaluate frequency of colonic adenomatous polyps and CRC in patients with acromegaly at first and subsequent colonoscopies; correlate risk factors of CRC and disease activity of acromegaly with colonoscopy findings and analyze relationship of acromegaly as a risk factor for CRC and the best period for screening this neoplasia.

Methods: Patients ≥18 years-old with acromegaly were included. A questionnaire involving characteristics of follow-up of acromegaly and risk factors of CRC was created. Biochemical and colonoscopic data were collected through medical records. Only full-length colonoscopies with satisfactory colonic preparation were included.

Results: 123 patients (77 women) were included (mean age at diagnosis of 43.1 years and mean follow-up of 13.7 years). In baseline colonoscopy, 80.5% had non-neoplastic findings, 14.6% non-advanced adenomas, 3.3% advanced adenomas and 1.6% CRC. At end of the study, 3 (2.4%) patients were diagnosed with CRC. No patient under 50 years had a neoplastic lesion on colonoscopy. We observed a positive statistically significant relationship between smoking (p = 0.026), age at diagnosis of acromegaly (p < 0.001), age at baseline colonoscopy (p = 0.002), and risk of adenomas and/or CRC at initial colonoscopy.

Conclusions: Smoking and advanced age were positively related to a higher risk of developing premalignant/malignant colonic lesions. Age ( > 50 years) was the most robust variable. Our data suggest that screening age for CRC in acromegaly should be reviewed.

Objectives: Inconsistent elevation of catecholamines (CAs) and metanephrines (MNs) was observed in pheochromocytomas/paragangliomas (PPGLs). This study aimed to explore its potential causes and report the diagnostic efficacy of MNs and CAs in a large Chinese PPGL cohort.

Methods: Clinical data and results of hormone tests were retrospectively collected. The sensitivity of plasma MNs and 24h-urinary CAs was analyzed. Clinical characteristics were compared between patients with positive and negative biochemical results, and among those with inconsistent elevation of MNs and CAs.

Results: Seven hundred and three patients were included, with a median onset age of 41.0 years. Plasma MNs (93% ~ 99%) showed prior diagnostic sensitivity to 24h-urinary CAs (74% ~ 89%). Patients with negative biochemical results presented as a smaller tumor (1.7 cm vs. 4.3 cm, P = 0.001), a higher proportion of normal blood pressure (60.0% vs. 20.5%, P = 0.002) and negative ¹³¹I-meta-iodobenzylguanidine (¹³¹I-MIBG) imaging (55.6% vs. 17.3%, P = 0.012). An earlier age of onset (40.0 vs. 41.0 vs. 44.5 years, P = 0.025), a higher proportion of paroxysmal hypertension (36.5% vs. 29.2% vs. 32.2%, P = 0.005) and the Epinephrine secretion type (79.3% vs. 37.7% vs. 48.0%, P < 0.001) were found in patients with the ratio of MNs/CAs elevation multiples <0.5 than those with the ratio between 0.5 and 2 or >2.

Conclusions: Plasma MNs exhibited a superior sensitivity than 24-h-urinary CAs in the Chinese PPGL diagnosis. Patients with a small tumor, normal blood pressure and negative ¹³¹I-MIBG imaging were prone to express negative biochemical levels. Additionally, an obvious elevation of 24-h-urinary CAs than plasma MNs was correlated to paroxysmal hypertension and the Epinephrine type.

Purpose: Osteoporosis imposes significant burdens. Early detection of high-risk individuals through simple indicators can greatly improve prognosis. Red cell distribution width (RDW), a standard component of a complete blood count, shows promise, yet remains underexplored. This cross-sectional study aimed to investigate the association between RDW and femoral neck and spinal bone mineral density (BMD).

Methods: Participants aged 20-79 years from the 2005-2010, 2013-2014, and 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) were included. BMD was measured using dual-energy X-ray absorptiometry (DXA).

Results: A total of 13,029 participants were included, comprising 6684 men, 3238 postmenopausal women, and 3107 premenopausal women, with the sample weighted to represent 98,712,128 people. After adjusting for covariates, RDW exhibited a negative association with femoral neck BMD in both men (β = -0.006; 95% CI: -0.010 to -0.002; p = 0.0053) and postmenopausal women (β = -0.005; 95% CI: -0.010 to -0.000; p = 0.0413). Subgroup and sensitivity analyses supported the robustness of these findings. A negative association between RDW and spinal BMD in men approached significance (β = -0.004; 95% CI: -0.008 to 0.000; p = 0.0557). Persistent trends were observed for RDW with spinal BMD in postmenopausal women and with both femoral neck and spinal BMD in premenopausal women.

Conclusions: Our study suggests a negative association between RDW and femoral neck BMD in both men and postmenopausal women. These findings highlight the potential of RDW as a marker for identifying individuals at higher risk of osteoporosis.

Purpose: Chronic lead exposure continues to be a global environmental concern. Previous studies reported high levels of lead exposure in people with diabetes. Frailty is one of the vital comorbidities of type 2 diabetes mellitus (T2DM); however, researchers have not determined whether lead exposure is a risk factor for frailty in people with T2DM.

Methods: This cross-sectional study explored the association between blood lead levels and frailty in a Shanghai diabetic population cohort. Individuals who met ≥3 of 5 predefined criteria (weight loss, exhaustion, low physical activity, slow walking speed and low grip strength) were defined as frailty.

Results: A total of 884 participants with T2DM (50.6% men, mean age 70.6 ± 7.4 years) were included. Among them, 147 (16.6%) patients were frail, and the median (interquartile range) concentration of blood lead was 16.0 µg/L (12.0-23.0). Compared with the participants within the lowest quartile of serum lead, positive associations of the 2nd and 4th lead quartiles with frailty were observed (OR, 95% CI; 1.70 1.01-2.84 and 1.72 1.03-2.88, respectively) after adjusting for age, sex and body mass index (BMI). After further adjustment for drinking status, smoking status, diet, education, blood pressure, triglycerides and glycosylated hemoglobin, the associations of serum lead with frailty were still significant for the 4th and 2nd-4th quartiles of lead (1.71, 1.01-2.91 and 1.57, 1.02-2.41, respectively). In the subgroup analyses, we found positive associations of serum lead with frailty in elderly individuals (1.77, 1.13-2.79), those with obesity (2.14, 1.02-4.51), those with unhealthy diets (2.52, 1.26-5.04), and those without hyperlipidemia (2.09, 1.12-3.88), although the interactions were not statistically significant (P for interaction all >0.05).

Conclusion: This work provides evidence of an association between chronic lead exposure and physical frailty in a diabetic population in a Chinese cohort. Future prospective and mechanistic studies are warranted to confirm our findings.

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.