Endocrine Connections最新文献

Background: Patients with congenital hypogonadotropic hypogonadism (CHH) are geographically dispersed and have unmet health and informational needs. Patients often rely on the internet to learn about CHH, find expert care, and connect with other patients.

Aims: We partnered with patients to co-design a website (virtual empowerment toolkit) and conducted an online evaluation of the website.

Methods: Healthcare providers, patients, and a design team engaged in an iterative 'design thinking' process (i.e., empathize, define, ideate, prototype, refine, test) to co-design the website. Subsequently, patients with CHH were recruited and evaluated the site using the 'gold standard' Patient Education Materials Assessment Tool for audio/visual materials (PEMAT-A/V). Scores ≥80% on PEMAT-A/V domains are considered 'high-quality'. Content analysis was used to group qualitative feedback into salient themes.

Results: Patients were involved from the outset and in all stages of the design thinking process. Iterative patient focus groups and online surveys were used to prioritize content and refine prototypes. In total, 58 participants (48.5±14.4 yrs.) completed the online evaluation. All PEMAT-A/V domains scored >88% (i.e., 'high-quality'). Participants (47/55, 86%) rated the site 'easy to navigate' and 52/55 (95%) would recommend the site to another patient. Qualitative feedback was largely positive and expressed appreciation for the online resource.

Conclusions: Partnering with patients to co-design the virtual patient empowerment toolkit produced an understandable, actionable website that was responsive to patient priorities. This work supports the utility of co-creation and co-design for empowering patients with CHH and may serve as a roadmap for other rare diseases.

Objectives: Preoperative alpha blockade is recommended for pheochromocytomas and paragangliomas (PPGL), whereas evidence for calcium channel blockers (CCBs) remains limited. This study evaluated perioperative haemodynamic outcomes with first-line amlodipine for preoperative blockade and identified predictors of intraoperative haemodynamic instability (iHDI).Methods/ Design: In this monocentric retrospective study, 35 operated PPGL patients who received preoperative first-line amlodipine (July 2021-March 2024) were analysed. Continuous intraoperative arterial pressure recordings were analysed for episodes and duration of hypertension, hypotension, and iHDI. Biochemical phenotype and tumour characteristics were assessed as predictors.

Results: The cohort (median age: 32 years; 60% female) included 32 pheochromocytomas and 3 sympathetic paragangliomas. Germline variants were detected in 20/34 tested patients (Cluster-1: 11; Cluster-2: 9). Amlodipine up to 20 mg was tolerated in all except two, with a median of 7 days to reach BP targets. Median iHDI duration was 6.67% (0-16.4). On linear regression, log-transformed plasma free metanephrine (PFMN) independently predicted iHDI duration (β=2.26, p=0.027). Patients with adrenergic phenotype (n=13) exhibited greater duration of SBP ≥160 mmHg (14 vs. 1 min), peak SBP (201 vs. 160 mmHg), and nitroglycerin dose (659 vs. 59.6 µg) than noradrenergic phenotype. Postoperative hypotension (37.1%) was associated with higher plasma free normetanephrine (3440 vs. 1242.9 ng/L) and larger tumour size (5.1 vs. 4.2 cm). No perioperative mortality occurred.

Conclusion: First-line amlodipine blockade was effective in preventing iHDI in PPGL. Plasma free metanephrine and normetanephrine correlated with intraoperative hypertension and postoperative hypotension, respectively.

Background: The relationship between gonadotropin-releasing hormone agonists (GnRH-as) and depression and suicide/self-injury (DASSI) remains controversial. This study aimed to investigate this potential association using data from the FDA Adverse Event Reporting System (FAERS) database.

Methods: Instances of DASSI linked with GnRH-as were identified from FAERS (2004Q1 to 2024Q1). Time-to-onset (TTO) analyses and disproportionality analysis (DPA) were employed to assess onset timing and signal values for adverse events. The influence of concurrent medications on DASSI was evaluated using the Ω shrinkage measure.

Results: A total of 5,454 DASSI cases linked to GnRH-as were identified. TTO analyses showed earlier onset of DASSI in females, children (<18), and adults (18-65) compared to males and elders (>65) (females vs males: 3.5 (0.5-29.5) vs 120.5 (0.5-441.5) days, P < 0.001; children vs elders: 10.5 (0.5-78.5) vs 129.5 (0.5-490.5) days, P < 0.001; adults vs elders: 7.0 (0.5-81.0) vs 129.5 (0.5-490.5) days, P < 0.001). DPA revealed stronger signals for depression and suicide/self-injury in females and oncology patients compared to males and non-oncology patients. Co-medication analysis identified depressive interactions with multiple drug combinations.

Conclusions: Although causality cannot be inferred from FAERS data and the results should be interpreted cautiously, we identified some signals of disproportionate reporting of DASSI for certain GnRH-a therapies. These hypothesis-generating findings may raise clinical awareness and inform a risk-informed monitoring framework (e.g., baseline assessment of mood and suicidality, patient/caregiver education on warning signs, and early follow-up) but require confirmation in well-designed epidemiologic studies.

Background: Rebounding involves repetitive bouncing on a trampoline, a low-impact and enjoyable exercise. The purpose of this study was to explore the effects of rebound exercise on body mass index (BMI) and balance in adults with overweight and obesity.

Method: This review searched for relevant articles in Scopus, PubMed, Web of Science, and EBSCO databases from January 2005 to January 2025. During the procedure, the terms "rebound", "trampoline", "training", "exercise", "obesity", and "overweight" were applied. This review also utilised the standardised mean difference (SMD) as the index of effect size. Revman 5.4 software was used to analyze the average difference of the selected literature data with 95% confidence interval (CI).

Results: In the selected nine articles, a total of 234 participants (61 males and 173 females) aged over 18 years with a BMI ≥25 kg/m2 were included. The study outcomes revealed that rebound exercise considerably reduced the BMI [SMD 0.48 (0.26, 0.69), p < 0.01, I2 = 56%] of individuals with overweight and obesity. Nevertheless, the subgroup analysis revealed different results for intervention periods under [SMD, 0.25 (-0.03, 0.53), p = 0.08, I2 = 21%] and over 12 weeks [SMD, 0.82 (0.48, 1.17), p < 0.01, I2 = 14%]. Rebound exercise also notably affected balance in adults with overweight and obesity [SMD -0.62 (-0.98, -0.26), p < 0.01, I2 = 0%].

Conclusion: Rebound exercise exhibited the potential to reduce BMI and improve balance among adults with overweight and obesity. Nonetheless, only intervention plans of over 12 weeks demonstrated significantly greater effects. Consequently, rebound exercise can be employed as a program to reduce BMI and improve balance among adults with overweight and obesity.

Background: Hypothyroidism often impairs quality of life (QoL). This network meta-analysis (NMA) evaluated the efficacy and safety of additional interventions alongside levothyroxine (LT4).

Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched for randomized controlled trials (RCTs) on the treatment of hypothyroidism. A Bayesian NMA was performed, reporting standardized mean differences (SMD) or risk ratios (RR) with 95% credible intervals (CrIs). Evidence certainty was assessed using CINeMA framework.

Results: 35 RCTs involving 3,508 patients were included. Compared with placebo, levothyroxine (LT4) + aerobic training (AT) + resistance training (RT) significantly reduced thyroid-stimulating hormone (TSH) levels (SMD = -3.97, 95% CrI: -5.76, -2.18, high certainty); LT4 + zinc (Zn) + magnesium (Mg) + vitamin A (VA) raised free thyroxine (FT4) (SMD = 1.95, 95% CrI: 1.37, 2.53, high certainty); LT4 + Zn increased free triiodothyronine (FT3) (SMD = 1.46, 95% CrI: 0.40, 2.51, low certainty). In addition, LT4 + AT + RT significantly improved QoL scores (SMD = 1.62, 95% CrI: 0.78, 2.46) and mental health scores (MHS) (SMD = 2.1, 95% CrI: 1.19, 3.01, CINeMA: low certainty) compared with LT4 alone. LT4+ RT significantly improved physical function score (PFS) (SMD = 1.59, 95% CrI: 0.76, 2.43). Liothyronine (LT3) increased adverse events versus placebo (RR = 15.54, 95% CrI: 2.68, 501.14, very low certainty).

Conclusion: The combination of LT4, AT, and RT may be the preferred strategy for reducing TSH, enhancing QoL, and improving MHS. Clinical interventions should be tailored based on individual patient profiles.

Background: The European Reference Networks on Rare Endocrine Diseases (Endo-ERN) and member healthcare provider (HCP)s, both are mandated to undergo periodical evaluation of their performance every 5 years. This evaluation is to ensure the continued high standards of ERN HCPs and gauges network progress. The first 5-year Evaluation took place in 2022 for Health care providers that joined Endo-ERN as full members in 2017. As the first implementation of this methodology, it must be reviewed and refined before the next 5-year Evaluation.

Aim: To investigate how the evaluation process could have impacted the changes in scores beyond merit of the HCP.

Methods: This mixed methods retrospective study and content analysis (CA) was used to examine the self-evaluation results from HCPs, comparing the draft and final scores earned.

Results: Fifty-eight HCPs that were subjected to the 5-year evaluation were included, with 14 receiving onsite-audit. Final scores of HCPs who received an onsite audit were significantly higher than draft scores in only one area, concerning 'Quality & Safety', [W =105, p < .0001]. CA found 5 different concepts potentially causing this difference. HCPs with onsite audit commented 'No evidence is provided' online frequently. In follow up, 61% of HCPs who received the onsite audit felt the onsite visit added value, however, in parallel 55% felt that the on-site audit is not necessary.

Conclusions: An onsite audit has some added value for evaluation activities, however it can place unnecessary burden on healthcare professionals in the current structure. This study now provides five key recommendations to improve the next ERN 5-year Evaluation.

Background and aims: This study aimed to explore whether a younger age of diabetes onset is associated with an increased risk of CVD events.

Methods: This study included 621 patients with younger-onset T2DM (age, ≤50 years) and 573 with older-onset T2DM (age, >50 years) from the original Da Qing Diabetes Prevention Study. For comparison, 310 younger individuals without diabetes (age, ≤50 years) were included in the control group. We followed up participants for 34 years to assess the incidence of CVD events. The association between the age of diabetes onset and the risk of CVD events was analysed.

Results: The younger-onset T2DM patients had a higher incidence of components of CVD events per 1,000 person-years than those of the older-onset T2DM and younger non-diabetes controls (19.20, 15.14, and 9.22 for stroke, 7.78, 4.67, and 2.15 for myocardial infarction, and 5.38, 2.76, and 1.11 for heart failure, respectively). The more than double high risk of composite CVD events was found in the younger-onset T2DM compared with the older-onset T2DM (HR = 2.05, 95% CI: 1.64-2.55) and non-diabetic controls (HR = 3.45, 95% CI: 2.39-4.98) even after adjusting for the strongest confounder diabetes duration.

Conclusions: Chinese adults with younger-onset T2DM have a higher risk of developing CVD events than those with older-onset T2DM over a 34-year follow-up period.

Aims: Chemotherapy regimens can induce severe hyperglycemia, which may be underestimated using conventional point-of-care blood glucose (POC-G) measurement techniques. Real-time continuous glucose monitoring (rtCGM) systems may offer a more accurate assessment of glucose metabolism. In this study, we compared blood glucose monitoring using POC-G and rtCGM in patients with rare endocrine cancers caused by chemotherapy and steroid medication.

Methods: In this single-center observational study, we analyzed data from 76 hospitalized patients with pancreatic neuroendocrine tumors (n = 48) or adrenocortical carcinoma (n = 28) undergoing chemotherapy. Patients were monitored using either POC-G (n = 38) or rtCGM (n = 38). Glycemic metrics included time in range (TIR), prevalence of steroid-induced hyperglycemia (SIH), and HbA1c.

Results: Using POC-G, TIR was 23.6 ± 0.9 h/day in patients without diabetes (NoD) and 20.0 ± 4.2 h/day in patients with diabetes undergoing chemotherapy (mean: five cycles). However, when rtCGM was used, drastic changes in TIR were documented under the same regimen. The mean TIR decreased from 21.7 h/day in patients with NoD to 14.6 h/day in patients with diabetes (P < 0.01). Similarly, the overall incidence of SIH was 30% using conventional POC monitoring, but this figure rose to 79% using rtCGM. During rtCGM use, HbA1c decreased by 0.3% over the course of the chemotherapy cycles, whereas during POC-G use, HbA1c increased by 0.2% (P < 0.01).

Conclusion: We demonstrated a previously underestimated frequency of hyperglycemia and SIH in patients undergoing chemotherapy by using rtCGM. The use of rtCGM enabled more detailed recognition of dysglycemia and may improve glucose metabolism during and after chemotherapy regimens.

Objective: To establish sex- and age-specific reference intervals for plasma concentrations of adrenocorticotropic hormone (ACTH) and direct renin in healthy youth.

Design: 529 healthy subjects (5.8-20.4 years) were recruited as part of the third Copenhagen Puberty Study, an ongoing cross-sectional study of healthy Danish participants attending compulsory school and high school.

Method: Plasma ACTH and direct plasma renin concentrations were established using GAMLSS statistics, sex- and age-specific reference intervals and standard deviation (SD) scores. Concentrations were evaluated according to pubertal stage and oral contraceptive (OC) use.

Results: ACTH concentrations did not differ between sexes. ACTH concentrations were higher in pubertal males than in prepubertal males (P = 0.015); however, this difference was not statistically significant when analyses were restricted to samples collected before 10:00 h. In females, ACTH concentrations did not seem to differ according to pubertal status. In both sexes, renin concentrations were lower in pubertal than in prepubertal subjects (females: P < 0.001; males: P = 0.016). Renin SD scores were lower in OC users than in non-OC users (P = 0.007), while ACTH SD scores did not differ between these groups.

Conclusion: Sex- and age-specific reference intervals for plasma concentrations of ACTH and direct renin in young, healthy subjects were provided, reflecting changed levels through puberty and significantly lower renin SD scores in OC users. Application of these biomarkers' SD scores may enhance the management of patients with adrenal disorders.

Significance statement: Reliable reference data for plasma ACTH and direct plasma renin in healthy children are limited. This large population-based cohort study of healthy participants attending compulsory school and high school provides comprehensive sex- and age-specific reference intervals for plasma ACTH and renin. Furthermore, absolute concentrations were converted to relative SD scores, thereby providing a more unified and standardized tool for clinical assessment. Reporting ACTH and renin concentrations by pubertal stage represents a novel aspect. These new reference intervals enhance the clinical utility of biomarker-based monitoring and treatment of pediatric endocrine disorders, such as congenital adrenal hyperplasia, addressing a critical gap in current clinical pediatric practice.

Clinical trial registration number: NCT04884620.