Endocrine Connections最新文献

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.

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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.

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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.

Background: Obesity and type 2 diabetes mellitus (T2DM) are burgeoning public health challenges. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) have gained prominence because they improve glycemic control and aid weight reduction by slowing gastric emptying and promoting satiety. Liraglutide is a once-daily human GLP-1 analogue marketed for T2DM (at 1.8 mg) and weight management (3.0 mg), whereas semaglutide is a more potent GLP-1 RA administered once weekly at doses of 1.0 mg (diabetes) and 2.4 mg (weight management). Randomized controlled trials suggest that semaglutide yields greater weight loss and HbA1c reduction than liraglutide [1, 2], yet comparative data in real-world South Asian populations are limited.

Methods: We performed a prospective, open-label, randomized study at Lady Reading Hospital, Peshawar, Pakistan. Adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with T2DM were randomized (1:1) to once-weekly semaglutide 2.4 mg plus lifestyle counselling or once-daily liraglutide 3.0 mg plus the same counselling. The primary outcome was the percentage change in body weight at 68 weeks. Secondary outcomes included proportions achieving weight-loss thresholds (≥ 5%, ≥ 10 % and ≥ 15 %) [3]; change in HbA1c [4], fasting glucose, waist circumference, blood pressure, lipid profile, patient-reported quality of life, and adverse events. Mean changes were compared using t-tests; categorical outcomes were compared using χ2 tests.

Results: Two hundred forty participants (mean age 45.6 ± 9.8 years, 52 % women) were enrolled. At 68 weeks, semaglutide recipients lost significantly more weight than liraglutide recipients (-14.7 ± 5.8 % vs -6.2 ± 4.9 %; p < 0.001), consistent with STEP 8 trial findings [1]. A greater proportion of semaglutide patients achieved ≥ 10 % and ≥ 15 % weight loss (70.9 % and 55 %) compared with liraglutide (25.6 % and 12 %) [3]. HbA1c decreased by -1.6 ± 0.4 % with semaglutide versus -1.0 ± 0.4 % with liraglutide (p < 0.001), mirroring SUSTAIN-10 differences [5]. Gastrointestinal adverse events were common but similar between groups (83.5 % vs 82.0 %); nausea and vomiting occurred more frequently with semaglutide [6].

Conclusions: In a real-world Pakistani cohort, once-weekly semaglutide produced substantially greater weight loss and HbA1c reduction than daily liraglutide, with comparable tolerability. These findings support the preferential use of semaglutide for weight management and glycemic control, particularly when once-weekly dosing improves adherence. Further studies should explore long-term sustainability, cardiovascular benefits, cost-effectiveness, and optimal integration with lifestyle interventions.

Background/objectives: Glucose-dependent insulinotropic polypeptide (GIP) is secreted by enteroendocrine K cells in response to nutrient ingestion. The aims of this study were: i) to evaluate the cross-sectional associations between plasma GIP change in response to an oral glucose challenge (as a surrogate of GIP secretion) with obesity-related anthropometric measurements, fasting inflammatory biomarkers, and fasting circulating adipokines; and ii) to evaluate the feasibility of using postprandial plasma GIP as a biomarker of adiposity-related phenotypes in response to starch-based meals.

Methods: Fifty normoglycemic women without obesity (19-32 years) were evaluated with an oral glucose tolerance test (OGTT). A feasibility study was conducted in a subset of eight women to estimate responses to starch-based meals (25 g of starch). Postprandial glycemic-related changes in plasma hormones/metabolites were assessed, and circulating adipokines and inflammatory biomarkers in fasting conditions.

Results: The incremental-GIP change after 2 h OGTT was significantly associated with waist circumference (rho = 0.34; P = 0.02), fasting plasma TNF-α (rho = 0.54; P = 0.0002), and white blood cell count (rho = 0.39; P = 0.008), but not with MCP-1, total adiponectin, leptin, or the free leptin index. A strong inverse association was found between incremental-GIP change and fasting plasma high-molecular-weight (HMW) adiponectin (rho = -0.50; P = 0.0004), which remained significant after adjusting for age and body mass index.

Conclusion: An inverse association was found between postprandial GIP levels and circulating HMW-adiponectin levels in humans. This work highlights the suitability of using postprandial plasma GIP as a biomarker for metabolic disturbances of increased adiposity, even in the absence of obesity.

Introduction: Most phaeochromocytomas produce insulin, and some produce glucagon-like peptide 1 receptor (GLP-1R). In pancreatic β-cells, stimulation of GLP-1R causes insulin release. A few phaeochromocytoma patients experience hypoglycaemic attacks. Therefore, we studied the distribution of GLP-1R-containing and insulin-containing phaeochromocytoma cells and their relation.

Methods: In 20 phaeochromocytomas, we performed sequential double staining with anti-insulin and anti-GLP-1R antibodies and, in selected cases, staining with anti-insulin alone. We quantified tumour cells with positive staining and compared their distribution to that of randomly distributed cells using simulations. We obtained GLP-1R transcript data from 182 such tumours from The Cancer Genome Atlas (TCGA) Research Network.

Results: GLP-1R-containing cells were found in six of the 20 tumours, and insulin-containing cells were found in fifteen. Moreover, in the TCGA cohort, almost half of the tumours produce GLP-1R transcripts, and patients with the highest number of transcripts show longer disease-free survival. In the tumours, we found that cells expressing insulin were present in the cytoplasm and GLP-1R in the membrane, with a frequency of 2.59 and 1.34%, respectively. These cells showed clustering, and one tumour showed a large clonal expansion. Interestingly, we found deposits of insulin, which we suggest naming insulin bodies in two tumours. Very few cells contained both proteins.

Conclusion: Most phaeochromocytomas contain tumour cells producing insulin. About half produce GLP-1R. The producing cells show clustering, and clonal expansion occurs. Insulin release might cause hypoglycaemia. Increased GLP-1R levels might induce less aggressive tumours.

Objective: Strain imaging serves as a sensitive marker for detecting early subclinical myocardial systolic dysfunction. The purpose of this study was to evaluate the diagnostic and prognostic value of myocardial work indices in assessing subclinical myocardial systolic dysfunction in active acromegaly patients.

Methods: 27 active acromegaly patients and 27 healthy controls matched for age, sex, height, weight, body mass index and body surface area were included in the study. Active acromegaly was diagnosed based on elevated serum insulin-like growth factor 1 (IGF-1) (>1× upper limit of normal) or insufficient GH suppression (nadir ≥0.4 ng/mL) during an OGTT. All participants underwent two-dimensional speckle-tracking echocardiography (2D-STE) for the assessment of cardiac function. STE extracted the corresponding strain parameters (such as global longitudinal strain (GLS), global circumferential strain and global radial strain) and work parameters (such as global work index, global constructive work, global wasted work (GWW) and global work efficiency (GWE)) by analyzing the motion (strain)-velocity (strain rate) of two or more local myocardial segments, combined with the left ventricular non-invasive pressure estimation technique. At the same time, correlation analysis was used to explore the factors affecting GWW and GWE in the acromegaly group.

Results: In comparison with the control group, conventional echocardiography revealed that acromegaly patients did not exhibit a significant difference in left ventricular ejection fraction (60.3 ± 3.7 vs 59.1 ± 4.8, P = 0.312), a commonly used index to evaluate ventricular systolic function, STE showed that there was no significant difference in GLS (-18.3 ± 2.4 vs -17.4 ± 2.9, P = 0.514) between the control group and the acromegaly group. However, significant differences can be found in GWW (44.8 ± 31.1 vs 80.6 ± 75.6, P = 0.027) and GWE (97.0 ± 1.8 vs 95.0 ± 3.8, P = 0.020), and a significant correlation was observed between myocardial work parameters and 1.5 × ULN IGF-1.

Conclusion: GWW and GWE are sensitive markers for identifying subclinical myocardial systolic dysfunction, suggesting their potential as early markers for detecting subclinical myocardial systolic dysfunction in active acromegaly patients.

Objective: Cystic fibrosis (CF) is a congenital condition caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF-related diabetes (CFRD) is a common comorbidity among people with CF (pwCF) and is associated with increased morbidity. Previous in vitro studies have suggested that CFTR dysfunction is involved in the pathogenesis of CFRD. This prospective study aimed to evaluate the role of CFTR in glucose homeostasis by comparing glucose, insulin, C-peptide, glucagon and GLP-1 responses during an oral glucose tolerance test (OGTT) in pwCF and healthy controls and in pwCF before and after initiating elexacaftor-tezacaftor-ivacaftor (ETI) therapy.

Methods: Twenty-four pwCF were enrolled, of which 18 underwent OGTT both before and after ETI initiation. Ten healthy controls were included for comparison. Plasma samples were collected at standard OGTT time points, including an additional 15 min sample. Hormonal and glucose responses during OGTT were compared across groups and in pwCF before and after starting ETI.

Results: Compared with healthy controls, pwCF exhibited impaired glucose regulation, delayed insulin secretion, decreased insulin sensitivity index and reduced disposition index, indicating beta-cell dysfunction. In addition, p-glucagon levels were elevated in pwCF. Following ETI therapy, pwCF showed improved glucose control, increased first-phase insulin secretion and normalized glucagon secretion.

Conclusions: These findings support a role for CFTR in islet hormone regulation, implicating direct effects on beta-cell function and a potential role in suppressing glucagon secretion.