Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and a leading cause of visual impairment among adults worldwide. While hyperglycemia and metabolic dysregulation are recognized contributors to DR pathogenesis, increasing attention has been directed toward the role of genetic factors. This review evaluates the association between specific single nucleotide polymorphisms (SNPs) and DR susceptibility within the Greek population, an underrepresented group in global genomic studies. The review synthesizes findings from population-specific research focused on eight genes, namely, ADIPOQ, AGER, ALDH2, UCHL3, HNMT, PAI-1 (SERPINE1), SLC2A1, and NOS3. Variants in these genes have been implicated in key pathways related to inflammation, oxidative stress, endothelial dysfunction, and glucose metabolism. Several polymorphisms, including ADIPOQ rs1501299, AGER rs1051993, ALDH2 rs671, and NOS3 rs1799983, were associated with increased DR risk, while others showed associations with disease progression or early onset. Importantly, some polymorphisms revealed ethnic-specific effects not observed in other populations, highlighting the importance of localized genetic studies. These findings are hypothesis-generating and further research is required to replicate these associations, clarify underlying mechanisms, and assess gene-environment interactions before considering any potential clinical translation.
The 13th Annual EndoBridge Meeting took place in Antalya, Türkiye, from October 23 to 26, 2025. Accredited by the European Council, the congress delivered a comprehensive scientific program combining state-of-the-art lectures with interactive small-group case discussions led by internationally recognized experts in endocrinology and metabolism. The meeting drew a diverse audience and provided an in-depth review of major areas within the field. Core subjects included disorders of the pituitary, thyroid, adrenal glands, and bone metabolism, as well as neuroendocrine tumors, diabetes, obesity, clinical nutrition, and lipid abnormalities. Clinical case abstracts presented in oral and poster sessions were subsequently published in JCEM Case Reports. This report highlights the principal themes and clinical insights shared during the congress. Key discussions addressed contemporary approaches to acromegaly management, therapeutic strategies for subclinical thyroid dysfunction, goal-oriented treatment models in osteoporosis, adjunctive options in type 1 diabetes management, and the evolving concept of obesity phenotyping. Additional updates covered hormonal treatment strategies for menopause and premature ovarian insufficiency, along with recent developments in male hypogonadism and infertility. Overall, the sessions reflected current advances in endocrine science while offering practical guidance for the management of common and complex endocrine disorders. The 14th Annual EndoBridge Meeting will be held in Antalya, Türkiye, from October 22 to 25, 2026.
To analyze the efficacy and safety of osilodrostat in patients with ectopic Cushing’s syndrome (ECS) in real-world studies. A scoping review focused on the treatment with osilodrostat for patients with ECS was conducted in MEDLINE (PubMed) and Scopus databases. The review was conducted following the Joanna Briggs Institute protocol for scoping reviews. A total of 12 articles with 46 patients (24 males and 22 females) with ECS were included. The age range was 11–85 years. Up to 70
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder characterized by complex metabolic, inflammatory, and fibrogenic interactions. Advances in lipidomics and proteomics have substantially refined understanding of MASLD pathophysiology by revealing how qualitative alterations in lipid species and dynamic protein signaling networks contribute to disease initiation and progression. Bioactive lipids, including ceramides and free cholesterol, promote lipotoxicity, mitochondrial dysfunction, inflammasome activation, and fibrosis, while proteomic analyses have identified key pathways involved in inflammation, cellular senescence, and hepatic stellate cell activation. Emerging translational evidence further suggests that modern pharmacological agents may modulate these molecular signatures beyond their metabolic effects. Integrating lipidomic and proteomic data may therefore facilitate improved disease stratification, biomarker discovery, and the development of mechanism-based therapeutic strategies, supporting a transition toward precision medicine in MASLD.
To describe the 18-month auxological response to recombinant human growth hormone (rhGH) therapy in a pediatric patient with genetically confirmed PRKAR1A-related acrodysostosis and partial growth hormone deficiency (GHD). A 3-year-9-month-old boy with genetically confirmed PRKAR1A-related acrodysostosis underwent comprehensive endocrine evaluation due to progressive growth deceleration. Growth hormone (GH) secretion was assessed using two pharmacological stimulation tests (glucagon and L-dopa). rhGH therapy was initiated and titrated based on clinical and biochemical response, with serial auxological and biochemical follow-up over 18 months. At presentation (3 years 9 months), height was − 2.92 SDS with a growth velocity of 3 cm/year over the preceding year. Two stimulation tests demonstrated peak GH levels of 8 ng/mL and 5.5 ng/mL, consistent with partial GHD. Brain MRI revealed mild anterior pituitary hypoplasia. After 18 months of rhGH therapy, height increased from 89 cm to 103.5 cm and height SDS improved from − 2.92 to − 1.52 (Δ + 1.40 SDS), with a first-year height velocity of 11 cm/year. Bone age advanced from 2 years 8 months at treatment initiation to 4 years 6 months at 18 months. Serum IGF-1 increased while remaining within the age-adjusted laboratory reference range, and no adverse effects were observed during follow-up. To our knowledge, this represents the second published pediatric case of type 1 acrodysostosis with documented partial GHD treated with rhGH. The marked auxological response over 18 months supports the concept that central GH axis impairment may coexist with the intrinsic skeletal pathology of the disorder in some patients.
Congenital hypothyroidism due to thyroid dyshormonogenesis is a rare inherited disorder that may present with goiter of variable severity. Massive congenital goiter causing life-threatening respiratory distress at birth is exceptionally uncommon. We report a late-preterm male neonate who presented immediately after delivery with severe respiratory failure requiring endotracheal intubation due to critical tracheal compression caused by a massive congenital goiter. Postnatal imaging revealed marked thyroid hyperplasia with airway narrowing. Thyroid function tests demonstrated isolated low free thyroxine (fT4) levels with normal thyroid-stimulating hormone (TSH), a pattern attributed to non-thyroidal illness syndrome related to perinatal asphyxia and inotropic support. Therapeutic-dose levothyroxine was initiated, resulting in a progressive reduction in goiter size and successful extubation. Genetic analysis using next-generation sequencing identified a previously unreported homozygous missense variant in the thyroglobulin gene, supporting the diagnosis of thyroglobulin-related dyshormonogenetic congenital hypothyroidism. This case highlights that congenital goiter should be considered in neonates presenting with respiratory distress at birth, even in the absence of elevated TSH levels or prenatal findings. It underscores the importance of early diagnosis, genetic evaluation, and timely levothyroxine therapy to prevent airway compromise and ensure favorable outcomes.
Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely used for the management of type 2 diabetes, metabolic syndrome, and obesity. Concerns regarding its potential association with thyroid cancer, particularly medullary thyroid carcinoma, have emerged, although current human evidence remains inconclusive. Reports of papillary thyroid carcinoma (PTC) while using semaglutide therapy are exceedingly rare. We describe a 40-year-old man with metabolic syndrome and obesity who had been treated with semaglutide for several years before discontinuation. A routine chest computed tomography (CT) performed for an unrelated diaphragmatic hernia identified a suspicious thyroid lesion, later confirmed by ultrasound as a 1 × 1 cm irregular hypoechoic nodule in the left lobe with several small ipsilateral lymph nodes demonstrating suspicious features. Fine-needle aspiration cytology revealed classic PTC (Bethesda VI). The patient underwent total thyroidectomy with left selective neck dissection and central compartment dissection. Histopathology confirmed a unifocal classic variant PTC, 16 mm in size, with negative margins, no lymph node involvement, and no extrathyroidal extension. After an uncomplicated postoperative course, he was prescribed levothyroxine for TSH suppression and discharged. This case of PTC discovered concomitantly while the patient was on semaglutide therapy highlights an important clinical scenario but does not provide evidence of causation. The totality of available human data continues to support the safety of semaglutide with respect to thyroid cancer risk. Further long-term surveillance and high-quality epidemiological studies remain warranted.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disorder globally and is strongly associated with obesity, type 2 diabetes mellitus, and the metabolic syndrome. Accurate and timely assessment of hepatic steatosis and fibrosis is critical for risk stratification and therapeutic monitoring. However, liver biopsy, the current reference standard, is invasive, subject to sampling variability, and unsuitable for repeated assessments of a large population. Non-invasive imaging modalities have emerged as potential alternatives, offering reproducibility and possibility for quantitative evaluation. Ultrasound-based techniques are focused on qualitative and sometimes quantitative assessment of liver fat, while elastography techniques are focused on liver stiffness, which is associated with fibrosis stage. Magnetic resonance techniques offer highly reproducible evaluation of steatosis, metabolic alterations, and fibrosis, with magnetic resonance imaging-proton density fat fraction regarded as the reference standard for fat quantification and magnetic resonance elastography providing the highest accuracy for fibrosis staging. Computed tomography also enables liver fat quantification; however, its use is limited mainly because of exposure to ionizing radiation. Recent artificial intelligence (AI) applications are oriented towards enhancing diagnostic accuracy and automate quantitative assessment while supporting longitudinal monitoring. Despite these advancements, further research is required to validate emerging techniques, standardize acquisition protocols, and ensure widespread clinical implementation. This review summarizes and synthesizes current evidence on non-invasive imaging diagnostic techniques for MASLD, highlighting their strengths, limitations, and potential integration into routine clinical practice in order to reduce dependence on invasive liver biopsy.
The association between serum vitamins and sex hormones has gained considerable research interest; however, studies focusing specifically on adolescent males remain limited. To analyze associations between key serum vitamins and sex hormone levels in adolescent males. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) (2001–2004). Weighted generalized linear regression models were employed to examine associations between serum vitamins (D, B12, folate, A, and E) and sex hormones, namely, total testosterone (TT), sex hormone-binding globulin (SHBG), and estradiol (E2). The Bayesian kernel machine regression (BKMR) model was employed to account for the combined effects of vitamins, nonlinear exposure-outcome relationships, and interactions among vitamins. A total of 231 participants aged 12–18 years were included. In the generalized linear model, vitamin A was positively correlated with TT (β = 0.421; 95
Type 2 diabetes mellitus (T2DM) is imposing a substantial and rapidly growing global health burden. Disease estimates vary widely across geographies and time periods, reflecting not only true differences in disease occurrence but also variation in demographic structures, risk factor exposures, diagnostic practices, surveillance capacity, and biological heterogeneity within T2DM itself. A narrative, integrative synthesis of global epidemiological evidence was conducted. Data were sourced from major international platforms, supplemented with peer-reviewed literature. Evidence was synthesized across time, place, and person, with explicit attention to differences in case definitions, biomarker use, screening intensity, and modeling assumptions. Conceptual frameworks were applied to interpret observed patterns. Harmonized NCD-RisC analyses show a sustained rise in age-standardized prevalence from 1980 to 2014, increasing from 4.3
Diabetes technology has transformed substantially over the past two decades, becoming central to modern diabetes management. Continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and smart insulin pens have reshaped both the assessment of glycemic control and diabetes treatment, particularly in people with type 1 diabetes (T1D) and selected individuals with insulin-treated type 2 diabetes (T2D). Among these technologies, CGM represents a major paradigm shift, providing continuous insight into glucose trends, variability, and time spent within clinically meaningful glycemic ranges, thereby complementing—and in many cases replacing—traditional self-monitoring of blood glucose. This narrative review summarizes evidence from randomized controlled trials and real-world studies regarding the evolution of CGM technology, insulin delivery strategies–including conventional insulin pumps, sensor-augmented pumps, and hybrid closed-loop systems—and the application of these technologies in specific clinical contexts, such as pregnancy, gestational diabetes, and perioperative and inpatient settings. While these systems offer clear metabolic and psychosocial benefits, important limitations remain, particularly those related to delayed insulin pharmacokinetics, sensor lag during rapid glucose changes, and user-dependent factors. Emerging developments, including fully closed-loop and dual-hormone systems as well as the growing role of artificial intelligence in CGM data analysis and risk prediction are also explored. Future development is expected to focus on improved personalization, tighter integration of technologies, and a transition toward more predictive and proactive diabetes care.
The aim of this study is to comprehensively investigate the independent associations between a wide array of novel metabolic indices and the prevalence of circadian syndrome (CircS), as well as to explore, within a cross‑sectional framework, whether the C‑reactive protein triglyceride glucose index (CTI) shows statistical associations consistent with mediation. A cross‑sectional analysis was conducted using data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 wave, involving 6,507 participants aged ≥ 45 years. Multivariable logistic regression, restricted cubic splines, and mediation analyses were employed to assess associations, non‑linearity, and indirect effects (cross‑sectionally consistent with mediation). In fully adjusted models, multiple metabolic indices — including dynapenic abdominal obesity, frailty, TyG‑related indices, and the cardiometabolic index (CMI) — showed significant positive associations with CircS prevalence (all P < 0.001), while CCR was inversely associated. Restricted cubic spline analyses revealed significant non‑linear relationships for all indices (log‑likelihood ratio test P < 0.001). Mediation analysis indicated that CTI had a statistically significant indirect effect (cross‑sectionally consistent with mediation), with the proportion of the total effect statistically attributable to CTI ranging from 20.8
Pheochromocytomas and paragangliomas (PPGLs) can trigger major cardiovascular events (MACEs) due to unpredictable release of catecholamines. The aim of this systematic review and meta-analysis was to determine prognostic factors associated with MACEs in PPGLs patients. A literature search was conducted in PubMed and the Cochrane Library from January 1980 to March 2026. Assessment of clinical, laboratory, imaging, histological, and genetic parameters was performed on the pooled data. Nine retrospective cohort studies involving 1566 patients with PPGL were included. MACEs were observed in 302 patients [pooled estimate of 21
Melatonin (N-acetyl-5-methoxytryptamine) plays a key role in lipid metabolism regulation, directly influencing fatty acid oxidation and lipid transport and modulating pathways related to energy homeostasis. This study aimed to evaluate its acute effects on tissue bioenergetics during post-exercise recovery. Thirty Wistar rats performed a 60-min swimming at 90
The rising prevalence of obesity and type 2 diabetes mellitus (T2DM) constitutes a major global public health concern. Increasing evidence indicates that genetic polymorphisms may modulate the risk of T2DM in individuals with obesity, providing valuable insight into the biological pathways that connect these interrelated disorders. A better understanding of the genetic determinants underlying obesity-associated T2DM could enhance disease characterization and inform risk stratification strategies. The genetic architecture linking obesity and T2DM has, however, not yet been fully elucidated. In this case-control study, we investigated the distribution of the TCF7L2 rs7903146, FTO rs9939609, and PPARG rs1801282 polymorphisms in 257 Greek adults with obesity (BMI > 30 kg/m²), including 136 individuals without T2DM and 121 with T2DM. The primary prespecified analysis applied unadjusted additive logistic regression to estimate per-allele odds ratios (ORs) for T2DM risk, while dominant and recessive inheritance models were evaluated as secondary analyses. Hardy-Weinberg equilibrium was assessed in the control group using an exact test. In participants without diabetes, genotype distributions were further compared across clinically defined HbA1c categories based on American Diabetes Association thresholds. The study was conducted and reported in accordance with STREGA guidelines. Genotype distributions differed significantly between cases and controls for all three loci. In the additive model, each additional T allele at TCF7L2 rs7903146 was associated with higher odds of T2DM (OR 2.66, 95
Gender-affirming hormone therapy (GAHT) alters sex-steroid exposure, raising important questions about skeletal health in transgender and gender-diverse populations. Evidence remains fragmented and centred on areal bone mineral density (BMD), with sparse fracture data and little integration of other parameters such as muscle. This narrative review synthesises evidence on skeletal health in transgender individuals, bone density, fracture risk and the muscle-bone unit, bone health screening, and effects of gonadotropin-releasing hormone (GnRH) agonists during adolescence. We performed a narrative review of clinical studies and guidelines addressing BMD, fractures, puberty suppression, and GAHT in transgender populations, prioritising clinically relevant data. Multiple cohorts report low pre-GAHT BMD, particularly in individuals assigned-male-at-birth (AMAB), likely reflecting minority stress, low physical activity, suboptimal vitamin D status, and sedentary lifestyles. Adequately dosed GAHT generally maintains or modestly improves BMD, especially in individuals assigned-female-at-birth (AFAB) on testosterone, while modest lumbar spine deficits may persist in some AMAB individuals. Fracture data are limited but reassuring. In adolescents, GnRH-agonists predictably reduce BMD Z-scores during hormonal suppression, with partial recovery after GAHT-initiation. However, implications for peak bone mass remain uncertain. Emerging evidence favours risk-stratified rather than universal dual-energy X-ray absorptiometry (DXA) screening, alongside optimisation of GAHT, nutrition, and physical activity. Current evidence does not indicate an increased skeletal risk when GAHT is appropriately managed. Pre-existing vulnerabilities appear central to bone health risk stratification, underscoring the need for risk-based care that integrates bone parameters alongside non-skeletal factors, such as muscle.
Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors, have been generally considered, since the 2017 WHO classification, as malignant neoplasms with various metastatic potential. Approximately 10–25
Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) release and, by extension, gonadotropin secretion. Although continuous kisspeptin administration has been shown to dampen kisspeptin-induced GnRH release in non-human primates [1, 2], this has not been replicated in the limited human studies reported to date. The objective of this study was to examine the effects of continuous kisspeptin administration on luteinizing hormone (LH) secretion in healthy men. Three healthy adult men received a continuous intravenous infusion of kisspeptin-10 at a dose of 12.5 mcg/kg/h for 24 h and underwent frequent blood sampling to characterize the effect on reproductive hormones. Continuous administration of kisspeptin resulted in an immediate increase in LH concentrations, from a baseline of 2.8–3.8 mIU/mL to the highest values of 17.5–30.6 mIU/mL (5- to eightfold above baseline), reached within 12–20 h of infusion onset. LH concentrations subsequently declined by 13–47
Destructive thyroiditis is among the most frequent endocrine adverse events of immune checkpoint inhibitors (ICIs). Most reports focus on thyroid dysfunction; less is known about how ICI-induced destructive thyroiditis may remodel thyroid architecture and alter pre-existing nodular disease. A 56-year-old woman with a previously documented high-risk thyroid nodule (13 mm, EU-TIRADS 5) was diagnosed with triple-negative breast cancer and started on neoadjuvant therapy including pembrolizumab. Several months into therapy, pre-operative routine testing revealed de novo asymptomatic overt primary hypothyroidism (TSH 123 mIU/L, fT4 0.14 ng/dL), leading to postponement of breast surgery. Levothyroxine was initiated (100 µg/day), normalizing fT4 within 2 weeks and allowing surgery to proceed, while TSH remained markedly elevated. Thyroid autoantibodies were negative; ICI-induced destructive thyroiditis was presumed. Follow-up ultrasound, performed for planned fine-needle aspiration of the EU-TIRADS 5 nodule, showed a markedly atrophic thyroid gland with no residual suspicious nodules, with the previously documented high-risk nodule no longer detectable. These changes were interpreted as sequelae of destructive thyroiditis. The patient remains asymptomatic on stable levothyroxine replacement, with controlled hypothyroidism, and no breast cancer recurrence at last follow-up. This case highlights that ICI-induced destructive thyroiditis can not only cause severe hypothyroidism but also dramatically remodel thyroid morphology, including regression of an EU-TIRADS 5 nodule. It also illustrates a real-world perioperative dilemma, namely, whether normal fT4, despite very high TSH, is sufficient to proceed with major surgery. Finally, it raises questions about optimal follow-up when a suspicious nodule vanishes following ICI-related thyroiditis.
