Endocrine Practice最新文献

Objectives: The recommended dose of tolvaptan for hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone is 15 mg. We evaluated the efficacy of an initial 7.5 mg dose and determined the frequency where sodium (Na+) correction exceeded safe limits, defined as an increment of ≥10 mmol/L, within the initial 8 or 24 hours of administration.

Methods: A retrospective review of patients with syndrome of inappropriate antidiuretic hormone treated in a single academic hospital in London. The initial dose was 7.5 mg and the second dose was 7.5 or 15 mg.

Results: One hundred eighty-one patients were included. With the initial dose, the mean Na + increase was 4.54 ± 3.70 mmol/L (P < .0001) after 4-12 hours, with 8.7% demonstrating an increase exceeding 10 mmol/L. Between 18-30 hours, the mean Na + increase was 6.15 ± 3.51 mmol/L (P < .0001), with 19.4% over-correcting. Over-correction was more likely in patients with a pre-dose Na + concentration of ≤127 mmol/L (OR 13.64, 95% CI 1.80-102.95). No cases of osmotic demyelination syndrome were observed. For patients needing a second dose, the increment in Na + concentration showed no significant difference between 7.5 and 15 mg (P = .532).

Conclusion: In our view, tolvaptan can be initiated with a 7.5 mg dose, accompanied by Na + monitoring at 12 and 24 hours. If a second dose is necessary, 7.5 mg is comparably effective to a 15 mg dose, depending on the initial response. Further monitoring should include Na + concentration at around 24 hours after the second dose.

Objective: People with chronic kidney disease (CKD) are at increased risk of fractures in comparison to the non-CKD population, and fractures are associated with high mortality and worsening quality of life. However, the approach for evaluation of bone disease and fracture risk in CKD is different from the approach in the general population.

Methods: The authors conducted a literature review of PubMed to include studies on pathophysiology of CKD mineral bone disorder, fracture risk assessment, and therapeutic options in the setting of CKD.

Results: The higher risk observed in the CKD population is related to the complex interplay of changes in bone turnover (T), mineralization (M), and volume (V), along with other risk factors accumulated as glomerular filtration rate declines. The diagnosis of the type of renal osteodystrophy is not based only on assessment of bone density and traditional risk factors for osteoporosis. There are limitations of currently available fracture risk tools in the CKD population. Treatment choice should take into consideration the 3 components of the TMV classification along with the stage of kidney disease and comorbidities, but the assessment of these components has not been well established.

Conclusions: Current data are limited on efficacy and safety of treatments for fracture prevention in CKD. As new medications for the treatment of osteoporosis become available, there is an urgency to establish more clear guidelines for the diagnosis, fracture risk stratification, and treatment of bone disease in CKD.

Objective: Dysglycemia has deleterious outcomes on critically ill patients with diabetes mellitus (DM). Insulin degludec, an ultralong-acting insulin, is associated with lower rates of hypoglycemia and blood glucose (BG) variability in non-critically ill patients. The experience with insulin degludec in the intensive care units is lacking. This study aimed to assess the effect of insulin degludec on glycemic control in critically ill patients with type 2 DM.

Methods: A prospective, interventional study enrolled critically ill patients with type 2 DM. Subjects were started on insulin degludec plus insulin regular correctional doses. BG levels were assessed every 6 hours. The primary outcome was the percentage of BG levels within a target of 140 to 180 mg/dL. The secondary outcomes included the median BG levels, severe hypoglycemia rate, and BG variability.

Results: In total, 155 patients were enrolled. The percentage of BG levels within the target was 28.5%. The first day that the median of BG levels within target was on day 2 of insulin degludec therapy, which continued to be within the target for 1 week. Severe hypoglycemia developed in 5 patients (3.2%). The BG variability in the study was 26% using the coefficient of variation.

Conclusion: In critically ill patients with type 2 DM, one-fourth of BG levels were within the glycemic target (140-180 mg/dL) with insulin degludec plus insulin regular correctional doses. The median BG levels were in target starting the second day of insulin degludec therapy. The favorable BG variability using insulin degludec merits further investigation for effect on clinical outcomes.

Objective: Thyroid stimulating hormone (TSH) is related to increased atrial fibrillation (AF) inducibility and plays an important role in a variety of cardiovascular diseases. However, the association of baseline TSH with in-hospital outcomes in patients with AF and coronary artery disease (CAD) is unknown. This study aimed to investigate the distribution of baseline TSH and its association with in-hospital outcomes (major adverse cardiovascular events, all-cause death, or heart failure [HF]) in AF patients combined with CAD.

Methods: A total of 19 725 patients with AF were included. The status of blood TSH was investigated. Patients with AF and CAD were divided into low, median, and high-TSH subgroups based on tertiles of baseline TSH levels. Clinical characteristics and in-hospital outcomes were compared. Logistic regression analysis was performed to determine the association of TSH with in-hospital outcomes. Subgroup analysis was also performed.

Results: In patients with AF and CAD, compared with the low-TSH group, the median-TSH (OR 0.277, 95% CI 0.078-0.991, P = .048) and high-TSH (OR 0.163, 95% CI 0.036-0.750, P = .020) groups were associated with decreased all-cause death. Besides, high TSH showed a protective role for HF events, and the same results were seen in females, age ≥75, and non-non-hypertension subgroups.

Conclusion: Higher baseline TSH presented a protective effect on in-hospital all-cause death and HF in patients with AF combined with CAD.

Objective: No meta-analysis has holistically analyzed and summarized the efficacy and safety of the novel once-weekly basal insulin efsitora alfa in managing type 1 diabetes (T1D) and type 2 diabetes (T2D).

Methods: Clinical trials involving subjects with T1D and T2D receiving once-weekly efsitora alfa in the intervention arm and once-daily basal insulins in the control arm were searched throughout the electronic databases. The primary outcome assessed was the change from baseline in glycated hemoglobin (HbA1c).

Results: Data from 6 studies (2465 subjects) were analyzed (follow-up 26-54 weeks). Once-weekly efsitora alfa and once-daily degludec achieved comparable HbA1c reduction in study subjects with T2D (mean difference [MD] 0.02% [-0.11, 0.16]; P = .74) and T1D (MD 0.11% [-0.01, 0.22]; P = .08). Efsitora and degludec were similarly effective in reducing fasting plasma glucose and achieving HbA1c < 7% in subjects with T2D. Individuals with T2D and T1D in the 2 groups had comparable time in range, time above range, and time below range. Subjects with T2D receiving efsitora and once-daily basal insulin had comparable total adverse events, severe adverse events, injection-site reactions, hypersensitivity events, and overall and severe hypoglycemia; however, nocturnal hypoglycemia risk was lower with efsitora (risk ratio 0.85 [0.74, 0.98]; P = .03). However, in individuals with T1D, total adverse events, severe adverse events, and injection-site reactions were higher with efsitora, with comparable risks of hypersensitivity events and overall, severe and nocturnal hypoglycemia.

Conclusion: Once-weekly basal insulin efsitora alfa is well tolerated with glycemic efficacy similar to once-daily degludec.

Objective: To assess glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) and sodium-glucose cotransporter protein-2 inhibitors (SGLT-2 inhibitors) in patients with metabolic dysfunction-associated steatotic liver disease or metabolic dysfunction-associated steatohepatitis (previously known as nonalcoholic fatty liver disease [NAFLD] and nonalcoholic steatohepatitis [NASH]), we performed a systematic review and network meta-analysis of randomized controlled trials.

Methods: The study searched Pubmed, Embase, the Cochrane Library, and Web of Science databases up to November 26, 2023. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias.

Results: Thirty-seven studies were included in the analysis. GLP-1 receptor agonists were found to be more effective than placebo in resolving NASH (relative risk: 2.48, 95% CI:1.86 to 3.30). Both drugs were superior to placebo in reducing liver fat content, as well as decreasing levels of liver enzyme. Network meta-analysis indicated that SGLT-2 inhibitors were more effective than GLP-1 receptor agonists in reducing alanine aminotransferase and aspartate aminotransferase levels. According to the surface under the cumulative probability ranking curve values, GLP-1 receptor agonists and SGLT-2 inhibitors consistently ranked among the top 2 in terms of reducing anthropometric data compared to other included drugs.

Conclusions: GLP-1 receptor agonists and SGLT-2 inhibitors have significant effects on reducing liver fat content and liver enzymes in NAFLD or NASH patients compared to placebo. GLP-1 receptor agonists were found to be superior to placebo in resolving NASH. SGLT-2 inhibitors were more effective than GLP-1 receptor agonists in reducing alanine aminotransferase and aspartate aminotransferase levels.

Objective: Graves disease (GD) is the most common cause of hyperthyroidism. Treatment options include antithyroid drugs (ATDs), radioactive iodine, and surgery. In this review, we focus on the medical aspects of managing GD.

Methods: The authors conducted a literature review of PubMed to include studies and review articles on GD management, ATDs, long-term safety of antithyroid drugs, hyperthyroidism in pregnancy, Graves ophthalmopathy, and special circumstances related to hyperthyroidism.

Results: In adjunction to ATDs, medical management for GD also includes beta-blockers, glucocorticoids, and iodine containing agents. ATDs are currently the preferred option for initial management of GD, reflecting a shift in practice observed in the United States over the past 2 decades. ATDs in appropriate doses are well-tolerated and safe when used for longer duration, during pregnancy, and other circumstances discussed in this article. Routine thyroid function tests are important for monitoring. Thyrotropin receptor antibody plays an essential role in determining duration of treatment and assessing the likelihood of recurrence.

Conclusion: Medical management of GD with antithyroid drug is safe and effective. Long-term use beyond 24 months in patients with elevated thyrotropin receptor antibody is a reasonable alternative option to surgery and radioactive iodine due to higher rates of remission.

Objectives: Predicting recurrence after antithyroid drug (ATD) cessation is crucial for optimal treatment decision-making in patients with Graves' disease (GD). We aimed to identify factors associated with GD recurrence and to develop a model using routine pretherapeutic clinical parameters to predict GD recurrence risk during the first year following ATD discontinuation.

Methods: This electronic health records-based observational cohort study analyzed patients with GD treated with ATDs at 3 U.S. academic centers. Demographic, clinical characteristics, and GD recurrence within 1 year following ATD discontinuation were assessed. Univariable and multivariable analyses were performed. A predictive model for GD recurrence was developed and visualized as a nomogram.

Results: Among the 523 patients included in the study, 211 (40.34%) discontinued treatment. Of these, the 142 (67.29%) that had a follow-up period exceeding 12 months after stopping ATD were used for the development of the predictive model. Among the patients included in the model, the majority were women (n = 111, 78.16%), with a mean age of 49.29 years (standard deviation 16.31) and baseline free thyroxine (FT4) levels averaging 3.39 ng/dl (standard deviation 2.25). Additionally, 79 of 211 patients (37.44%) experienced recurrence within 1 year. Multivariable analysis indicated a 31% increased risk of GD recurrence per additional decade of age (odds ratio 1.31, 95% confidence interval 1.03-1.66, P = .0258), and a 65% increased risk of GD recurrence for every 2.0 ng/dL rise in baseline FT4 (odds ratio 1.65, 95% confidence interval 1.08-2.50, P = .0192). The recurrence predictive model's area under the curve was 0.69 in the derivation dataset and 0.65 in cross-validation.

Conclusions: This study introduced a practical model that can be used during the initial therapeutic decision-making process. It utilizes easily accessible baseline clinical data to predict the likelihood of GD recurrence after 1 year of ATD therapy. Further research is needed to identify other factors affecting risk of recurrence and develop more precise predictive models.

Objective: In moderate-to-severe Graves' orbitopathy (GO), rituximab is recommended as second-line therapy in patients non-responsive to intravenous glucocorticoids. We aimed to evaluate rituximab as early second-line therapy, as data is scarce and contradictory.

Methods: In this non-randomized, controlled, interventional study, patients with GO started on intravenous glucocorticoids. After 4 weeks, patients with <2 points improvement in clinical activity score (CAS) were switched to rituximab [Non-Responders Rituximab (NR-RTX) group] and were compared to the remaining patients who continued with intravenous glucocorticoids for 12 weeks [Responders-Glucocorticoid (R-GC) group]. A retrospective group of non-responsive patients who were provided regular care with intravenous glucocorticoids for 12 weeks was used as control [Non-Responders-Regular Care (NR-RC) group]. Background data and CAS were recorded for all groups at 0, 4, 12, 18, and 68 weeks. Quality of life (QoL) and safety data were collected from the NR-RTX and R-GC groups.

Results: The NR-RTX group (n=12) was similar to the others at baseline except for a 1-point lower median CAS compared to the NR-RC group (n=12) (p=0.03), and for having twice as many men compared to the R-GC group (n=13) (p=0.03). At 4 weeks, a linear mixed model indicated that the R-GC group had a 1.21-point (95%CI: -2.40 to -0.02) lower value for CAS compared to the NR-RTX group. CAS for all groups converged over time. Similar models for QoL revealed no treatment or time effects.

Conclusion: Switch to RTX early in the treatment course did not result in better CAS or QoL, compared to continuous intravenous glucocorticoids.