Endocrine Connections最新文献

Background: Epidermal growth factor (EGF) plays a crucial role in cellular growth, differentiation, and pancreatic β-cell maintenance. Despite reports on EGF deficiency in diabetic animal models, its relevance in type 2 diabetes (T2D), particularly in relation to obesity, remains underexplored. The present study aimed to evaluate plasma EGF levels in individuals with and without T2D, assess its associations with glycaemic status and clinical parameters, and evaluate the influence of obesity on these relationships.

Methods: A total of 838 eligible participants were selected from the Kuwait Diabetes Epidemiology Program. Of those, 428 were included in a 1:1 case-control analysis (214 T2D and 214 non-diabetics). EGF was measured in plasma using ELISA. Associations between EGF with glycaemic and clinical variables were evaluated using Pearson's correlation, multiple linear regression, and logistic regression analyses.

Results: Plasma EGF levels were significantly lower in individuals with T2D compared to non-diabetics (P < 0.001). Among non-diabetics, obese participants had a significantly lower EGF level than their non-obese counterparts (P = 0.03), while no such difference was observed in T2D. EGF negatively correlated with fasting blood glucose in both non-diabetics (P = 0.004) and T2D individuals (P < 0.001). In T2D, EGF negatively correlated with haemoglobin A1C (HbA1C) (P = 0.001), triglyceride (TG) (P = 0.021), and waist-to-hip ratio (WHR) (P = 0.014). Logistic regression confirmed that lower EGF levels were independently associated with T2D but not with general obesity (OR = 0.996, P = 0.001).

Conclusion: Reduced EGF levels are associated with poor glycaemic control in T2D. These findings highlight EGF's potential as a biomarker for glycaemic dysregulation and support further investigation into its role in diabetes pathophysiology and complications.

RTN4IP1 encodes a mitochondrial oxidoreductase essential for Coenzyme Q biosynthesis; pathogenic variants have been reported mainly in optic neuropathy and encephalopathy. We describe a 30-year-old woman carrying three novel pathogenic RTN4IP1 variants by exome sequencing (c.1163G>A p.Arg388Gln, c.949A>C p.Met317Leu, c.1109T>C p.Phe370Ser), who presented with panhypopituitarism, optic-nerve hypoplasia, corpus callosum agenesis, bicuspid aortic valve disease, seizures, and muscle pain, already on conventional hormone replacement. Coenzyme Q10 (CoQ10) (200 mg) was administered orally for six months; outcomes were assessed using BPI, WOMAC, TUG, LEFS, grip-strength dynamometry, SF-36, CPK and LDH and after six months of daily 200 mg CoQ10 the patient showed marked reductions in pain (BPI 4 → 0.8; -80 %) and muscle-damage markers (CPK 254 → 110 U/L) together with gains in grip strength (+49 %) and lower-extremity function (LEFS 31 → 60; +94 %). SF-36 domains related to physical health showed marked gains, while emotional scores remained stable. This is the first report linking RTN4IP1 mutations to endocrine failure and suggesting a therapeutic role for CoQ10 in mitochondrial-related endocrine disease.

Purpose: Ketosis-prone diabetes (KPD) is a new subtype of diabetes distinct from traditional type 2 diabetes, and the role of muscle mass in KPD remains unclear. Serum creatinine-to-cystatin C ratio (CCR) has been identified as a marker of muscle mass. The present study aims to investigate the value of CCR in newly diagnosed KPD.

Methods: Two hundred and ninety patients with newly diagnosed T2D were included in the study and were divided into T2D (n = 195) and KPD (n = 95) groups according to the occurrence of ketosis. The cutoff value of CCR in identifying KPD was analyzed by receiver operating characteristic (ROC) curves. Logistic regression was used to assess the relationship between CCR and KPD and the independent influences on KPD.

Results: The serum CCR level of the KPD group was significantly higher than that of the T2D group. After adjustment for all confounders, the risk of KPD was significantly increased with elevated CCR levels. The optimal cutoff value for CCR was 69.775 for male and 63.365 for female, with areas under the ROC curve of 0.639 for male and 0.648 for female. Postprandial blood glucose and CCR were independent risk factors, whereas age and postprandial C-peptide were independent protective factors for the KPD.

Conclusion: High levels of CCR are significantly associated with the odds of KPD, suggesting that higher muscle mass (estimated by CCR) may be linked to higher KPD incidence. Our study suggests that CCR may be a useful marker for the incidence of KPD, providing new insights into the mechanisms of KPD.

Objective: To evaluate health-related quality of life (HRQoL) in adolescents with idiopathic isolated growth hormone deficiency (IIGHD) who tested GH-sufficient, comparing those who discontinued recombinant human growth hormone (rhGH) at mid-puberty with those who continued until near-adult height (NAH).

Design: This multicentre prospective study used a patient-preference design. Previous findings showed NAH did not differ between groups. Height influences quality of life (QoL), particularly during adolescence when appearance and social comparison affect psychological development. The impact of height and treatment decisions on HRQoL during puberty remains unclear.

Methods: Adolescents with IIGHD who had received rhGH for ≥3 years and tested GH-sufficient in mid-puberty chose to continue or discontinue treatment. HRQoL was assessed at mid-puberty and NAH using QoLISSY (patient and parent reports), supplemented by KIDSCREEN-52, SDQ, and EQ-5D-Y.

Results: Of 127 participants, 44 continued rhGH and 83 discontinued. Questionnaire completion was 58% (n=74) at mid-puberty and 66% (n=84) at NAH. No significant differences in patient-reported QoL were observed between groups at either time point. Parents reported higher QoL in the discontinuation group at mid-puberty. Overall, QoL scores were within normal ranges and positively correlated with height SDS at both time points.

Conclusions: Discontinuing rhGH in adolescents with IIGHD who tested GH-sufficient at mid-puberty does not appear to negatively affect perceived QoL. Parental reports suggest greater well-being in the discontinuation group, possibly reflecting pre-existing satisfaction with height and health. These findings emphasize considering both physical and psychosocial factors in treatment decisions and incorporating patient and parent perspectives during puberty.

Background: This study evaluated the effects of vitamin D supplementation on oxidative stress, inflammation, and pregnancy outcomes in women with gestational diabetes mellitus (GDM).

Methods: In a randomized, double-blind, placebo-controlled trial, 229 women with GDM were assigned to receive 200 IU of vitamin D twice daily or a placebo for six weeks alongside standard care. Biomarkers and pregnancy outcomes were assessed.

Results: Vitamin D supplementation significantly increased serum 25(OH)D and calcium levels, improved oxidative stress markers (increased GSH, decreased MDA), and reduced hs-CRP compared to placebo. The vitamin D group had lower neonatal birth weight and a reduced incidence of macrosomia. No significant differences were found in fasting glucose changes or most other obstetric outcomes.

Conclusion: A six-week vitamin D supplementation in women with GDM improved vitamin D status, ameliorated oxidative stress and inflammation, and was associated with reduced neonatal birth weight and macrosomia, without significantly affecting glycemic control.

Objective: To identify factors independently associated with quality of life (QoL) impairment in Graves' hyperthyroidism (GH) patients and develop a clinically applicable nomogram for outpatient settings.

Methods: A total of 402 GH patients were recruited from the outpatient clinic of Endocrinology department of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, from January 2024 to June 2025. Participants were surveyed using a general information questionnaire, the Thyroid-Specific Patient-Reported Outcome Short-Form (ThyPRO-39), the Pittsburgh Sleep Quality Index (PSQI), the Hamilton Depression Scale (HAMD), and the Hamilton Anxiety Scale (HAMA). Univariate and multivariate analyses identified independent predictors of QoL impairment. A nomogram was developed and validated using the area under the receiver operating characteristic curve (AUC), bootstrap-calibrated plots, and decision curve analysis (DCA). An online dynamic calculator (dynnom) was also developed to facilitate clinical application.

Results: Multivariate analysis revealed that thyroid eye disease (TED), goiter, sleep disturbances, anxiety, and depressive symptoms were independent predictors of QoL impairment. The nomogram demonstrated excellent discriminative ability: AUC was 0.886 in the training group and 0.844 in the validation group. Bootstrap calibration showed good consistency between predicted and observed probabilities. DCA revealed favorable net clinical benefit across a 0.2-0.6 threshold range. The associated online calculator further improved clinical usability.

Conclusions: The nomogram integrating TED, goiter, sleep, and emotional factors provides a reliable tool for early identification of GH patients at high risk of QoL impairment in outpatient settings. Future external multicenter validation is needed to improve its generalizability.

Graphical abstract:

Abstract: The increased detection of adrenal incidentalomas and drug-induced adrenal insufficiency increases the demand for cortisol testing. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) and dynamic testing remain the gold standard, more expedient tools are needed. We compared the Elecsys Cortisol II immunoassay (ElecsysCort II) with LC-MS/MS during dynamic testing and evaluated the diagnostic performance of baseline cortisol cutoffs (0 min cortisol during a short Synacthen test). The study included 547 overnight dexamethasone suppression tests (44% abnormal), mainly performed in adrenal incidentaloma patients (69%), and 519 Synacthen tests (32% abnormal). ElecsysCort II slightly underestimated cortisol compared with LC-MS/MS with a Passing-Bablok regression of -3.20 (95% CI: -3.66 to -2.83) + 0.96X (95% CI: 0.96-0.97) and a mean relative difference of -8.22% (95% CI: -8.99% to -7.45%) by Bland-Altman, which was within the limits of acceptable bias based on biological variation. Agreement was not affected by glucocorticoid or estradiol intake. Compared with LC-MS/MS, ElecsysCort II demonstrated a specificity of 100%, sensitivity of 84%, positive predictive value of 99%, and negative predictive value of 86% for an abnormal overnight dexamethasone suppression test (480 min cortisol ≥50 nmol/L). For an abnormal Synacthen test (30 min cortisol <420 nmol/L), the measures were 95, 99, 89, and 100%, respectively. A baseline cortisol cutoff >300 nmol/L to rule out and <150 nmol/L to rule in adrenal insufficiency demonstrated a high specificity (>92%) and a positive predictive value (>87%). Our study supports the use of ElecsysCort II in general and baseline cortisol as a screening tool for adrenal insufficiency. The high proportion of abnormal overnight dexamethasone suppression tests among incidentaloma patients warrants further research.

Graphical abstract:

Abstract: Hyperthyroidism adversely affects quality of life (QoL), encompassing physical, mental and social functioning and well-being. Patients with hyperthyroidism often complain of anxiety, physical symptoms and tiredness. Concurrent thyroid eye disease (TED) further reduces QoL. With treatment of hyperthyroidism, QoL improves. Symptoms of hyperthyroidism, overall QoL and tiredness are among the domains that improve with a high effect size. Notwithstanding, the overall reduction in QoL persists compared to a matched general population, which seems to relate to residual tiredness, mental fatigue and concerns about levothyroxine substitution, ophthalmological symptoms and weight gain. Common factors contributing to reduced QoL in the long term have been described and include a high prevalence of thyroid dysfunction, the psychological burden of chronic illness, TED, possible inability of levothyroxine replacement to restore euthyroidism in all tissues, and central nervous system residual damage and/or dysfunction. The aetiology and treatment modality for hyperthyroidism may also play a role. In addition, a recently highlighted contributor and predictor of poor QoL is excessive weight gain, which given the global epidemic of obesity, mandates further attention. Regarding newer therapies for hyperthyroidism, notably radiofrequency ablation and molecular targeted immunotherapies, there is a dearth of objective data on QoL. New or improved tools for assessing QoL may be needed to better capture all concerns of these patients. There is a need for randomized controlled studies to guide practitioners regarding which pharmacological or non-pharmacological interventions offer the best long-term QoL outcomes in hyperthyroidism. Anti-obesity medications to mitigate weight gain could also be considered for such patients.

Plain language summary: Thyroid overactivity (hyperthyroidism) worsens patients' QoL, which usually improves after treatment. However, QoL is not completely restored for many patients. The reasons are multiple, including excessive weight gain. New approaches in treating hyperthyroidism are needed to address the long-term effects on QoL.

Objective: Primary adrenal insufficiency (PAI) in children, most commonly caused by congenital adrenal hyperplasia (CAH), is challenging to treat due to the short half-life of hydrocortisone and the difficulty in mimicking the physiological rhythm of cortisol. Continuous subcutaneous hydrocortisone infusion (CSHI) has shown benefits in CAH adults but remains poorly studied in children. The aim of our study was to evaluate the feasibility, safety, and clinical efficacy of CSHI in pediatric patients under oral treatment with poorly controlled PAI.

Methods: We conducted a retrospective monocentric study including 13 children and adolescents with PAI who were switched from oral hydrocortisone to CSHI between 2017 and 2024 due to a lack of disease control. Hormonal and clinical parameters were monitored over a median follow-up of 48 months.

Results: The median age at CSHI initiation was 11.08 (7.75-14.08) years. Eleven patients (84.6%) had CAH. The median duration of CSHI was 48 (6-54) months. Biochemical control improved, morning cortisol increased, while ACTH, 17-OHP, androstenedione, and testosterone levels decreased during follow-up. Growth velocity and BMI remained stable. In one patient with prior and recurrent adrenal crises, these events ceased. In boys with testicular adrenal rest tumors, tumor volume decreased or resolved. One adolescent girl with amenorrhea resumed regular menstrual cycles under CSHI. CSHI was well tolerated with no major complications.

Conclusion: CSHI offers a promising therapeutic alternative for children with PAI who are poorly controlled on oral therapy. It provides more physiological cortisol delivery, improves hormonal control, and appears safe during long-term pediatric use. Larger prospective studies are needed to confirm these findings and evaluate quality-of-life outcomes.