Journal of the Endocrine Society最新文献

Objective: This study aimed to determine if a combination of 2 abnormal lipid profiles revealed a stronger association with low bone mass than a single blood lipid abnormality alone.

Methods: This study enrolled 1373 participants who had received a dual-energy x-ray absorptiometry scan from January 2016 to December 2016 in a medical center in southern Taiwan. Logistic regression was used to examine association between lipid profiles and osteopenia or osteoporosis after adjusting for covariates.

Results: Compared to people with total cholesterol (TC) < 200 mg/dL, those with TC ≥ 240 mg/dL tended to have osteopenia or osteoporosis (OR 2.61; 95% CI, 1.44-4.71). Compared to people with low-density lipoprotein cholesterol (LDL-C) < 130 mg/dL, those with LDL-C ≥ 160 mg/dL tended to develop osteopenia or osteoporosis (OR 2.13; 95% CI, 1.21-3.74). The association of increased triglyceride and decreased bone mass was similar, although not statistically significant. Those with the combination of TG ≥ 200 mg/dL and TC ≥ 240 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 3.51; 95% CI, 1.11-11.13) than people with only one blood lipid abnormality. Similarly, people with TG ≥ 200 mg/dL and LDL-C ≥ 160 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 9.31; 95% CI, 1.15-75.42) than people with only one blood lipid abnormality, after adjustment for the same covariates.

Conclusion: Blood levels of TC, LDL-C, and TG were associated with osteopenia or osteoporosis. Results indicate that individuals aged older than 50 years with abnormal lipid profiles should be urged to participate in a bone density survey to exclude osteopenia or osteoporosis.

Context: A subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists.

Objective: We looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS.

Methods: A total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A_1c (HbA_1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of β-cell function (HOMA-2β) were computed using serum C-peptide.

Results: Metabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA_1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P < .001) in the PCOS group. Total body fat (%), 2hPGPG, HbA_1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2β. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P < .001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without.

Conclusion: Elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association.

Context: Moon-like facies (MLF) are a typical side effect of glucocorticoid (GC) therapy; however, its predisposing factors, relationship with GC-induced complications, and effects on body image are not well understood.

Objective: This study aimed to determine the predisposing factors for MLF during GC therapy; its association with GC-induced diabetes, hypertension, and dyslipidemia; and its effects on body image.

Methods: This prospective observational study spanned 24 weeks and targeted patients who received GC therapy at the University of Yamanashi Hospital from June 2020 to August 2022. The MLF was defined based on the following 3 factors: (1) an increase in facial measurement lengths, (2) subjective facial changes by patients' self-assessment using a visual analog scale; (3) objective and qualitative facial changes assessed by physicians. We examined the predisposing factors for MLF and the association of MLF with GC-induced diabetes, hypertension, dyslipidemia, and body image.

Results: The cumulative incidence rate of MLF at 24 weeks was 37.6%. Predisposing factors for MLF were an initial oral prednisolone dosage of ≥ 30 mg/day [odds ratio (OR) 63.91, 95% confidence interval (CI) 5.82-701.81] and female (OR 6.66, 95% CI 1.35-32.79). MLF showed a significant association with the onset of GC-induced diabetes (OR 6.58, 95% CI 1.25-34.74). MLF was also an independent factor contributing to body image disturbance (β = -18.94, P = .01).

Conclusion: MLF contributes to body image disturbance and is associated with the development of GC-induced diabetes; therefore, it is clinically important as a physical manifestation of GC therapy.

Pancreatic cancer is currently the seventh leading cause of cancer death worldwide. Understanding whether modifiable factors increase or decrease the risk of this disease is central to facilitating primary prevention. Several epidemiological studies have described the benefits of physical activity, and the risks associated with sedentary behavior, in relation to cancer. This study aimed to assess evidence of causal effects of physical activity and sedentary behavior on pancreatic cancer risk. We conducted a two-sample Mendelian randomization study using publicly available data for genetic variants associated with physical activity and sedentary behavior traits and genetic data from the Pancreatic Cancer Cohort Consortium (PanScan), the Pancreatic Cancer Case-Control Consortium (PanC4), and the FinnGen study for a total of 10 018 pancreatic cancer cases and 266 638 controls. We also investigated the role of body mass index (BMI) as a possible mediator between physical activity and sedentary traits and risk of developing pancreatic cancer. We found evidence of a causal association between genetically determined hours spent watching television (hours per day) and increased risk of pancreatic cancer for each hour increment (PanScan-PanC4 odds ratio = 1.52, 95% confidence interval 1.17-1.98, P = .002). Additionally, mediation analysis showed that genetically determined television-watching time was strongly associated with BMI, and the estimated proportion of the effect of television-watching time on pancreatic cancer risk mediated by BMI was 54%. This study reports the first Mendelian randomization-based evidence of a causal association between a measure of sedentary behavior (television-watching time) and risk of pancreatic cancer and that this is strongly mediated by BMI. Summary: Pancreatic cancer is a deadly disease that is predicted to become the second leading cause of cancer-related deaths by 2030. Physical activity and sedentary behaviors have been linked to cancer risk and survival. However, there is limited research on their correlation with pancreatic cancer. To investigate this, we used a Mendelian randomization approach to examine the genetic predisposition to physical activity and sedentariness and their relation to pancreatic cancer risk, while excluding external confounders. Our findings revealed a causal link between the time spent watching television and an increased risk of pancreatic cancer. Additionally, we determined that over half of the effect of watching television on pancreatic risk is mediated by the individual's BMI.

Context: Sexual and ancestral differences in driver gene prevalence have been described in many cancers but have not yet been investigated in pheochromocytoma and paraganglioma (PPGL).

Objective: This study aims to assess whether sex and ancestry influence prevalence of PPGL driver genes and clinical presentation.

Methods: We conducted a retrospective analysis of patients with PPGL considering studies from 2010 onwards that included minimal data of type of disease, sex, mutated gene, and country of origin. Additional features were recorded when available (age, tumor location, bilateral or multifocal, somatic or germline, and metastatic disease).

Results: We included 2162 patients: 877 in Europe and 757 in Asia. Males presented more often with germline pathogenic variants (PVs) in genes activating hypoxia pathways (P = .0006) and had more often sympathetic paragangliomas (P = .0005) and metastasis (P = .0039). On the other hand, females with PPGLs due to MAX PVs were diagnosed later than males (P = .0378) and more often developed metastasis (P = .0497). European but not Asian females presented more often with PPGLs due to PVs in genes related to kinase signaling (P = .0052), particularly RET and TMEM127. Contrary to experiences from Europe, Asian patients with PPGL due to PVs in kinase signaling genes NF1, HRAS, and FGFR1 showed a high proportion of sympathetic tumors, while European patients almost exclusively had adrenal tumors (P < .005).

Conclusion: Personalized management of patients with PPGL might benefit from considering sexual and ancestral differences. Further studies with better clinically aligned cohorts from various origins are required to better dissect ancestral influences on PPGL development.

Objective: Results of ethanol ablation (EA) for controlling neck nodal metastases (NNM) in adult patients with papillary thyroid carcinoma (APTC) beyond 6 months have rarely been reported. We now describe outcome results in controlling 71 NNM in 40 node-positive stage I APTC patients followed for 66 to 269 months.

Methods: All 40 patients were managed with bilateral thyroidectomy and radioiodine therapy and followed with neck ultrasound (US) for >48 months after EA. Cumulative radioiodine doses ranged from 30 to 550 mCi; pre-EA 27 patients (67%) had 36 additional neck surgeries. Cytologic diagnosis of PTC in 71 NNM selected for EA was confirmed by US-guided biopsy. EA technique and follow-up protocol were as previously described.

Results: The 40 patients had 1 to 4 NNM; 67/71 NNM (94%) received 2 to 4 ethanol injections (total median volume 0.8 cc). All ablated 71 NNM shrank (mean volume reduction of 93%); nodal hypervascularity was eliminated. Thirty-eight NNM (54%) with initial volumes of 12-1404 mm³ (median 164) disappeared on neck sonography. Thirty-three hypovascular foci from ablated NNM (pre-EA volume range 31-636 mm³; median 147) were still identifiable with volume reductions of 45% to 97% observed (median 81%). There were no complications and no postprocedure hoarseness. Final results were considered to be ideal or near ideal in 55% and satisfactory in 45%. There was no evidence of tumor regrowth after EA.

Conclusion: Our results demonstrate that for patients with American Joint Committee on Cancer stage I APTC, who do not wish further surgery or radioiodine, and are uncomfortable with active surveillance, EA can achieve durable control of recurrent NNM.

Background: Rebound hyperglycemia may occur following glucagon treatment for severe hypoglycemia. We assessed rebound hyperglycemia occurrence after nasal glucagon (NG) or injectable glucagon (IG) administration in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods: This was a pooled analysis of 3 multicenter, randomized, open-label studies (NCT03339453, NCT03421379, NCT01994746) in patients ≥18 years with T1D or T2D with induced hypoglycemia. Proportions of patients achieving treatment success [blood glucose (BG) increase to ≥70 mg/dL or increase of ≥20 mg/dL from nadir within 15 and 30 minutes]; BG ≥70 mg/dL within 15 minutes; in-range BG (70-180 mg/dL) 1 to 2 and 1 to 4 hours postdose; and BG >180 mg/dL 1 to 2 and 1 to 4 hours postdose were compared. Incremental area under curve (iAUC) of BG >180 mg/dL and area under curve (AUC) of observed BG values postdose were analyzed. Safety was assessed in all studies.

Results: Higher proportions of patients had in-range BG with NG vs IG (1-2 hours: P = .0047; 1-4 hours: P = .0034). Lower proportions of patients had at least 1 BG value >180 mg/dL with NG vs IG (1-2 hours: P = .0034; 1-4 hours: P = .0068). iAUC and AUC were lower with NG vs IG (P = .025 and P < .0001). As expected, similar proportions of patients receiving NG or IG achieved treatment success at 15 and 30 minutes (97-100%). Most patients had BG ≥70 mg/dL within 15 minutes (93-96%). The safety profile was consistent with previous studies.

Conclusion: This study demonstrated lower rebound hyperglycemia risk after NG treatment compared with IG.

Clinical trial registration: NCT03421379, NCT03339453, NCT01994746.

Context: In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state.

Objective: To evaluate whether cord blood proprotein convertase subtilisin/kexin-type 9 (PCSK9), which is regulated by inflammation and metabolic derangements, is elevated in neonates born to overweight, obese, or diabetic mothers.

Methods: A retrospective study in full-term neonates born between 2010 and 2023, at Brigham and Women's Hospital. There were 116 neonates included in our study, of which 74 (64%) were born to overweight/obese mothers and 42 (36%) were born to nonoverweight/nonobese mothers.

Results: Neonates born to overweight/obese mothers had significantly higher cord blood concentrations of PCSK9 compared with neonates born to nonoverweight/nonobese group (323 [253-442] ng/mL compared with 270 [244-382] ng/mL, P = .041). We found no significant difference in cord blood concentrations of PCSK9 between neonates of diabetic mothers compared with neonates of nondiabetic mothers. In multivariate linear regression analysis, higher cord plasma PCSK9 concentration was significantly associated with maternal overweight/obesity status (b = 50.12; 95% CI, 4.02-96.22; P = .033), after adjusting for gestational age, birth weight, male sex, and intrauterine growth restriction.

Conclusion: Neonates born to mothers with overweight/obesity have higher cord blood PCSK9 concentrations compared with the nonoverweight/nonobese group, and higher cord blood PCSK9 concentrations were significantly associated with maternal overweight/obesity status, after adjusting for perinatal factors. Larger longitudinal studies are needed to examine the role of PCSK9 in the development of metabolic syndrome in high-risk neonates born to overweight, obese, or diabetic mothers.

Context: Rural-urban disparities have been reported in cancer care, but data are sparse on the effect of geography and location of residence on access to care in thyroid cancer.

Objective: To identify impact of rural or urban residence and distance from treatment center on thyroid cancer stage at diagnosis.

Methods: We evaluated 800 adults with differentiated thyroid cancer in the iCaRe2 bioinformatics/biospecimen registry at the Fred and Pamela Buffett Cancer Center. Participants were categorized into early and late stage using AJCC staging, and residence/distance from treating facility was categorized as short (≤ 12.5 miles), intermediate (> 12.5 to < 50 miles) or long (≥ 50 miles). Multivariable logistic regression was used to identify factors associated with late-stage diagnosis.

Results: Overall, 71% lived in an urban area and 29% lived in a rural area. Distance from home to the treating facility was short for 224 (28%), intermediate for 231 (28.8%), and long for 345 (43.1%). All 224 (100%) short, 226 (97.8%) intermediate, and 120 (34.7%) long distances were for urban patients; in contrast, among rural patients, 5 (2.16%) lived intermediate and 225 (65.2%) lived long distances from treatment (P < .0001). Using eighth edition AJCC staging, the odds ratio of late stage at diagnosis for rural participants ≥ 55 years was 2.56 (95% CI, 1.08-6.14) (P = .03), and for those living ≥ 50 miles was 4.65 (95% CI, 1.28-16.93) (P = .0075). Results were similar using seventh edition AJCC staging.

Conclusion: Older age at diagnosis, living in rural areas, and residing farther from the treatment center are all independently associated with late stage at diagnosis of thyroid cancer.

[This corrects the article DOI: 10.1210/jendso/bvad163.].