J. Endocrinol. Invest. [JOURNAL]
Sun
200 papers
Evaluation of rare NR1D2 variants in MODY-X: clinical, genetic, and in silico insights.
Aydogan C, Kanca-Demirci D, Gul N … +6 more , Poyrazoglu S, Tokat B, Mutlu U, Ozturk O, Yilmaz-Aydogan H, Satman I
J Endocrinol Invest · 2026 Jun · PMID 41649749 · Full text
PURPOSE: The objective of this study was to investigate the protein-coding regions of the NR1D2 gene in patients clinically diagnosed with maturity-onset diabetes of the young (MODY), including those without pathogenic v...
PURPOSE: The objective of this study was to investigate the protein-coding regions of the NR1D2 gene in patients clinically diagnosed with maturity-onset diabetes of the young (MODY), including those without pathogenic variants in known MODY genes (MODY-X), and to characterize the potential functional relevance of detected variants. METHODS: The variants present in the exons and adjacent intronic regions of the NR1D2 gene in patients with MODY were subjected to comparative analysis with those observed in healthy individuals and patients with type 2 diabetes mellitus. The maximum credible allele frequency was set to be 0.0001. The potential impact of rare variants was evaluated using variety in silico prediction tools, including PolyPhen-2, SIFT, MutationTaster2025, FATHMM-XF, REVEL, CADD, and DynaMut2. RESULTS: Two extremely rare NR1D2 missense variants were identified in three MODY-X patients: p.I148V (rs148928938) in exon 4 and p.R286W (rs768518229) in exon 5, with allele frequencies of 74 per million and 3 per million in gnomAD, respectively. In silico predictions indicated a more consistent deleterious profile for p.I148V, whereas p.R286W demonstrated heterogeneous and predominantly benign or borderline predictions. The clinical manifestations exhibited by the carriers were found to be variable, which is consistent with the metabolic heterogeneity that is characteristic of MODY. CONCLUSION: The findings suggest that these variants may function as metabolic modifiers contributing to phenotypic variability in MODY-X. Prospective family-based studies and functional assays are needed to clarify their biological significance.
Epidemiology of chronic hypoparathyroidism in Italy: a systematic review and meta-analysis.
Topini TCM, Stagni P, Dobreva M … +4 more , Galeone C, Cipriani C, Pirri S, Sanna MD
J Endocrinol Invest · 2026 Jun · PMID 41642436 · Full text
PURPOSE: Hypoparathyroidism (HPT) is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH). PTH is the primary regulator of the calcium/phosphate balance, acting directly on bone and kidney, and...
PURPOSE: Hypoparathyroidism (HPT) is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH). PTH is the primary regulator of the calcium/phosphate balance, acting directly on bone and kidney, and indirectly on the intestine. Regarding the epidemiology of chronic HPT, there are limited data in Italy. This study aimed to establish incidence and prevalence of chronic HPT in Italy. METHODS: A systematic literature review was conducted to identify the current knowledge regarding the epidemiology of chronic HPT in Italy, and a random effect meta-analysis was performed to estimate the pooled incidence. A subgroup analysis of non-surgical and postsurgical HPT estimates for patients was also conducted. RESULTS: We identified 4 studies eligible for inclusion reporting data from 15,412 patients with HPT. Considering a thyroidectomy rate of 57 per 100,000 and the incidence of post-surgical chronic HPT (≥ 6 months after surgery) at 1.2% (95% CI: 0.7%-1.8%), the number of incident post-surgical chronic HPT was estimated in 353 cases. Based on a mean time with chronic HPT after diagnosis of 17.4 years, a total of 6,142 prevalent post-surgical chronic HPT patients has been estimated for Italy. Findings from this analysis showed 4,383 prevalent non-surgical chronic HPT cases in Italy. The prevalence of chronic HPT, both surgical and non-surgical, in the adult population in Italy has been estimated to be 10,524 cases. CONCLUSION: This study provides a current estimate of the prevalence and incidence of chronic HPT in Italy. In this analysis, postsurgical chronic HPT accounted for the majority of prevalent cases. Epidemiological studies with appropriate study design are necessary to provide a validated estimation of the prevalence and incidence of HPT in Italy.
Endocrine late-effects in survivors of childhood and adolescence cancer: clinical management.
Biasin E, Felicetti F, Cattoni A … +9 more , Aloj G, Giorgiani G, Gorio C, Haupt R, Mastronuzzi A, Muraca M, Pillon M, Terenziani M, on the behalf of the AIEOP Late Effects Working Group
J Endocrinol Invest · 2026 Jun · PMID 41642435 · Publisher ↗
Five-year survival rates after childhood cancer have improved in recent decades: despite these promising survival rates, survivorship is associated with a lifelong increased risk of morbidity and mortality due to late ef...
Five-year survival rates after childhood cancer have improved in recent decades: despite these promising survival rates, survivorship is associated with a lifelong increased risk of morbidity and mortality due to late effects of cancer and its treatments. Numerous studies have elucidated the long-term health consequences, and endocrine disorders are identified as among the most prevalent ones, impacting over 40% of this population of survivors. Notwithstanding these findings, many healthcare providers remain unaware of the specific endocrinological recommendations and follow up needs of childhood cancer survivors, with the risk of inadequate monitoring and worsening health issues. This manuscript firstly aims to address the late endocrine complications and we would like to present the Italian experience in developing survivorship care model: by sharing these insights, we hope to enhance understanding and improve care strategies for managing the long-term endocrine health of childhood cancer survivors.
Circulating miR-326 and miR-532-3p: novel biomarkers for early gestational diabetes mellitus detection with high diagnostic accuracy.
Lin HZ, Liang ZK, Huang JJ … +11 more , Yang Y, Huang Y, Wu ZS, Tan JL, Huang S, Ruan SH, Xu BY, Ruan ZF, Huang TS, Wang QG, Xie L
J Endocrinol Invest · 2026 Feb · PMID 41642434 · Publisher ↗
PURPOSE: Gestational diabetes mellitus (GDM) significantly threatens maternal and fetal health, necessitating early and accurate diagnostic tools. This study aimed to identify and validate circulating microRNAs (miRNAs)...
PURPOSE: Gestational diabetes mellitus (GDM) significantly threatens maternal and fetal health, necessitating early and accurate diagnostic tools. This study aimed to identify and validate circulating microRNAs (miRNAs) as novel biomarkers for GDM. METHODS: A two-phase cross-sectional study enrolled 55 GDM patients and 55 matched healthy pregnant controls. In the discovery phase, RNA sequencing (RNA-seq) of peripheral blood RNA from a randomly selected subset (5 GDM patients, 5 controls) identified differentially expressed miRNAs. The validation phase employed reverse transcription and quantitative PCR (qPCR) in the entire cohort to confirm identified miR-326 and miR-532-3p expression. Bioinformatics analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]) investigated their functional roles using a consensus-based approach across multiple databases. RESULTS: RNA-seq revealed significant upregulation of miR-326 (mean normalized counts = 14.59, P < 0.05; log[Fold Change] = 0.93, P < 0.01) and miR-532-3p (mean normalized counts = 46.45, P < 0.05; log[Fold Change] = 0.66, P < 0.01) in GDM patients, a finding corroborated by cross-referencing with the Gene Expression Omnibus (GEO) database. qPCR validation confirmed significantly higher expression for both miRNAs in GDM (P < 0.001), with strong negative correlations to fasting, 1-hour and 2-hour postprandial glucose levels. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic performance (area under the curve [AUC]: 0.95 [95% CI: 0.91-0.99] for miR-326 and 0.96 [95% CI: 0.93-0.99] for miR-532-3p), robustly confirmed by bootstrap resampling. Functional analyses linked these miRNAs to phosphoinositide 3-kinase (PI3K)/Akt and Rap1 signaling pathways. CONCLUSION: This study provides compelling evidence for circulating miR-326 and miR-532-3p as a synergistic pair of biomarkers for GDM. Their high diagnostic accuracy and mechanistic insights into metabolic dysregulation position them as a promising complementary tool for early GDM risk assessment and for understanding GDM pathophysiology.
Metabolic and pathophysiological characterization of constitutional thinness.
Buscemi S, Randazzo C, Baido RL … +9 more , Grutta S, Barile AM, Colombrita P, Ligotino A, Cangemi S, Ferro S, Caruso R, Lombardo M, Buscemi C
J Endocrinol Invest · 2026 Jun · PMID 41642433 · Full text
PURPOSE: Constitutional thinness (CT) is characterized by a persistently low body weight in the absence of eating disorders or overt disease. Distinguishing CT from anorexia nervosa (AN) is often challenging, and the met...
PURPOSE: Constitutional thinness (CT) is characterized by a persistently low body weight in the absence of eating disorders or overt disease. Distinguishing CT from anorexia nervosa (AN) is often challenging, and the metabolic and cardiovascular features of CT remain incompletely defined. The present study investigated nutritional, metabolic, and cardiovascular parameters in women with CT and compared them with those of women with AN and normal-weight healthy controls. METHODS: Data from 7 women with CT were compared with those from 6 women with AN and 6 normal-weight healthy women serving as controls. The resting metabolic rate (RMR) and endothelial function, assessed by flow-mediated dilatation (FMD), were measured. RESULTS: Body weight, body mass index, fat mass and fat-free mass (FFM) were comparable between the CT and AN groups and significantly lower than those of the control group. Absolute and FFM-normalized RMR values were significantly higher in the CT group (median [IQR]: 1263 [247] kcal/24 h and 29.2 [3.1] kcal/FFM-kg/24 h) than in the AN group (1046 [272] kcal/24 h and 25.4 [2.7] kcal/FFM-kg/24 h; P < 0.001 and P < 0.05, respectively), and did not differ from those observed in controls (1317 [221] kcal/24 h and 29.5 [1.2] kcal/FFM-kg/24 h). Flow-mediated dilatation was significantly lower in both the CT (7.2 [2.7] %) and AN (7.6 [6.2] %) groups compared with controls group (14.0 [9.0]%; P < 0.05). CONCLUSION: These findings indicate that RMR differs between CT and AN, with women with CT exhibiting a metabolic profile distinct from that of AN and similar to that of normal-weight controls. Endothelial dysfunction was observed in both CT and AN, suggesting a potential cardiovascular alteration that warrants further investigation.
Incretin-based therapies in patients with pituitary disorders: clinical opportunity or premature enthusiasm? A balanced perspective.
Iglesias P
J Endocrinol Invest · 2026 Jun · PMID 41636997 · Publisher ↗
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Henagliflozin enhances frontal neural activation and cognitive function versus gliclazide in type 2 diabetes patients with mild cognitive impairment: A 16-week randomized controlled trial.
Chao Y, Jiao J, Zhang B … +6 more , Sun J, Tong X, Yang H, Wu T, Zhang Z, Bi Y
J Endocrinol Invest · 2026 Apr · PMID 41619161 · Publisher ↗
AIMS: Head-to-head comparisons of neuroprotective efficacy of glucose-lowering agents remain lacking in type 2 diabetes (T2D) patients with mild cognitive impairment (MCI). Here, we investigated the effects of henagliflo...
AIMS: Head-to-head comparisons of neuroprotective efficacy of glucose-lowering agents remain lacking in type 2 diabetes (T2D) patients with mild cognitive impairment (MCI). Here, we investigated the effects of henagliflozin or gliclazide on brain functional alterations and cognitive changes in these patients. MATERIALS AND METHODS: Twenty-four T2D patients with MCI were randomized (1:1) to receive henagliflozin or gliclazide treatment for 16 weeks. We assessed anthropometric and metabolic profiling, global and domain-specific cognitive testing, olfactory performance, and structural and functional magnetic resonance imaging (fMRI) at baseline and follow-up. The primary outcome was the between-group difference in odor-task fMRI activation at week 16. RESULTS: Treatment with henagliflozin for 16 weeks significantly increased odor-task fMRI activation in the left frontal white matter (Gaussian random field corrected) compared to gliclazide. Subsequent seed-based analysis revealed reduced functional connectivity to the left middle frontal gyrus, suggesting altered frontal network integration. These functional brain alterations were accompanied by significant improvements in global cognition (Montreal Cognitive Assessment [MoCA]: Δ + 2.1 vs. Δ − 0.2, P = 0.002) and delayed memory (Δ + 5.7 vs. Δ − 2.7, P = 0.012) in henagliflozin compared to gliclazide. Exploratory analyses suggested potential associations between concomitant metabolic improvements and cognitive/neuroimaging alterations, which merit further investigation. CONCLUSIONS: Our study showed that henagliflozin enhanced frontal brain activity and improved cognition (global and domain-specific: delayed memory) in T2D patients with MCI over 16 weeks, whereas gliclazide did not. These findings highlight the potential of henagliflozin for cognitive protection in this high-risk population. REGISTRATION: ClinicalTrials.gov (NCT06085703).
Influence of hormonal levels on atherosclerotic risk markers and platelet activation related to diabetic complications in patients with type 1 diabetes.
Baldimtsi E, Ekman B, Whiss PA … +1 more , Wahlberg J
J Endocrinol Invest · 2026 Jun · PMID 41619160 · Full text
BACKGROUND AND AIMS: Patients with childhood-onset type 1 diabetes (T1D) are at increased risk of developing microvascular complications, including neuropathy and nephropathy. Hormonal dysregulation and markers of athero...
BACKGROUND AND AIMS: Patients with childhood-onset type 1 diabetes (T1D) are at increased risk of developing microvascular complications, including neuropathy and nephropathy. Hormonal dysregulation and markers of atherosclerotic plaque instability and platelet activation may play key roles in the pathogenesis of these complications. The aim of this study was to investigate the impact of hormonal levels on atherosclerotic risk markers and platelet function, as well as to explore the association between diabetic neuropathy and nephropathy in individuals with childhood-onset type 1 diabetes. METHODS: In this cross-sectional analysis of a longitudinal cohort, 34 individuals with childhood-onset type 1 diabetes (mean age 27.6 ± 4.2 years; diabetes duration 8.2 ± 5.6 years) were examined. S-IGF-I, long-term HbA1c, micro/macroalbuminuria, triiodothyronine and thyroxine, S-Cortisol, P-ACTH, P-Renin, sP-Selectin, P-MMP-9, P-TIMP-1, P-Adiponectin, and platelet adhesion to albumin, collagen, and fibrinogen were assessed. An abnormality in nerve conduction tests was defined as diabetic neuropathy. RESULTS: S-IGF-I was negatively correlated with age (r = -0.36, p = 0.007), and with long-term HbA1c (r = -0.426, p = 0.019, corrected for age). IGF-I levels in patients diagnosed with clinical neuropathy (n = 6) were lower (123 ± 38 µg/L) than in patients without neuropathy (n = 26, 178 ± 56 µg/L, p = 0.029). S-IGF-I levels were also lower in patients with nephropathy (n = 7, 122 ± 28 µg/L) compared with patients without nephropathy (n = 27, 180 ± 60 µg/L, p = 0.02). S-IGF-I was negatively correlated with P-TIMP-1 (r = -0.44, p = 0.009), sP-Selectin (r = -0.53, p = 0.001), and positively correlated with platelet adhesion to fibrinogen (r = 0.38, p = 0.035). S-free-Triiodothyronine correlated negatively with P-MMP-9, (r = -0.46, p = 0.005), and P-MMP-/P-TIMP-1 ratio (r = -0.40, p = 0.018), and P-Adiponectin (r = -0.49, p = 0.018). P-Renin correlated negatively with P-Adiponectin (r = -0.34, p = 0.045). CONCLUSIONS: Low serum IGF-I levels were associated with the presence of diabetic neuropathy and nephropathy in young adults with type 1 diabetes. Additionally, both IGF-I and S-free-Triiodothyronine levels were linked to changes in platelet activation and atherosclerotic markers, suggesting that hormonal dysregulation may contribute to early vascular complications in this population.
Morning cortisol and central adrenal insufficiency: new thresholds from low-dose ACTH test and second-generation assay.
Gasco V, Bioletto F, Lucisano D … +11 more , Camoirano D, Cuboni D, Varaldo E, Sibilla M, Aversa LS, Mocellini F, Berton AM, Prencipe N, Ghigo E, Maccario M, Grottoli S
J Endocrinol Invest · 2026 Jun · PMID 41619159 · Full text
PURPOSE: According to current guidelines, a morning serum cortisol < 30 µg/L confirms central adrenal insufficiency (CAI), whereas a value > 150 µg/L rules it out. However, these thresholds are based on older assays, and...
PURPOSE: According to current guidelines, a morning serum cortisol < 30 µg/L confirms central adrenal insufficiency (CAI), whereas a value > 150 µg/L rules it out. However, these thresholds are based on older assays, and intermediate values require further testing. Newer, specific monoclonal antibody immunoassays may have lower diagnostic thresholds. This study aimed to identify morning cortisol cut-offs with ≥ 95% specificity or sensitivity (SP/SE) to determine which patients may safely avoid ACTH stimulation testing, using a second-generation immunoassay. METHODS: We retrospectively evaluated 435 adults (236 males; overall median age 58.5 [IQR 20.3] years) with pituitary disorders. Based on the 1 µg ACTH test, patients were classified as having or not having CAI using a peak cortisol cut-off of 180 µg/L (guideline) or 127 µg/L (Roche Elecsys® Cortisol II–based studies). RESULTS: With the 180 µg/L threshold, a morning cortisol ≤ 80.8 µg/L best predicted CAI (SE 37.1%, SP 95.2%), while > 144.0 µg/L best excluded it (SE 95.2%, SP 29.1%). Using the 127 µg/L threshold, a value ≤ 60.9 µg/L best predicted CAI (SE 54.7%, SP 96.3%), whereas > 141 µg/L (SE 96.2%, SP 21.2%) best ruled it out. CONCLUSIONS: We identified updated morning cortisol thresholds, specific to a second-generation immunoassay, that accurately predict ACTH test results and may streamline the diagnostic workup of suspected CAI. Based on these data, we propose a refined diagnostic algorithm.
Sarcopenic obesity increases the risk of falls in early-onset type 2 diabetes.
Chen X, Zhang Y, Zheng B … +4 more , Shen X, Huang L, Zhao F, Yan S
J Endocrinol Invest · 2026 Jun · PMID 41591735 · Publisher ↗
AIMS: This study aimed to investigate the association between early-onset type 2 diabetes (EOT2D) and the risk of falls, focusing on the role of sarcopenic obesity. METHODS: A total of 580 patients (290 with EOT2D and 29...
AIMS: This study aimed to investigate the association between early-onset type 2 diabetes (EOT2D) and the risk of falls, focusing on the role of sarcopenic obesity. METHODS: A total of 580 patients (290 with EOT2D and 290 with late-onset type 2 diabetes [LOT2D]) were selected through propensity score matching. Participants were categorized into four groups: non-sarcopenia/non-obesity, obesity-only, sarcopenia-only, and sarcopenic obesity. Binary logistic regression models were employed to examine the relationships between age at diabetes onset, sarcopenic obesity, and fall risk. Additionally, 472 patients were followed longitudinally to assess the associations between EOT2D, LOT2D, sarcopenic obesity, and fall risk. RESULTS: Patients with EOT2D exhibited a higher prevalence of sarcopenic obesity compared to those with LOT2D. EOT2D was significantly associated with an increased risk of falls, both directly and indirectly via sarcopenic obesity (β = 0.81, OR = 2.25, 95% CI: 1.79-2.82). EOT2D patients with sarcopenic obesity, particularly characterized by visceral fat area (VFA), demonstrated a substantially higher fall risk (HR = 3.98; 95% CI: 2.57-6.16) compared to those with sarcopenia or obesity alone. CONCLUSIONS: Patients with EOT2D are more prone to developing sarcopenic obesity, and visceral obesity contributes to the elevated risk of falls in this population. Therefore, interventions to preserve muscle mass and strength while reducing visceral fat accumulation are critical in mitigating fall risk among patients with EOT2D.
Novel identified micropeptide LEAO reshapes plasticity of adipose tissue to improve metabolic homeostasis.
Liu S, Song B, Hu L … +9 more , Zhao Z, Li J, Li X, Qian B, Cai Y, Lin J, Wu Q, Sun X, Yang Z
J Endocrinol Invest · 2026 Jun · PMID 41591734 · Publisher ↗
Adipose tissue exhibits remarkable plasticity, defined as its capability of adapting to various environments and energy demands by undergoing shifts in phenotypic, metabolic characteristics, and structure. However, obesi...
Adipose tissue exhibits remarkable plasticity, defined as its capability of adapting to various environments and energy demands by undergoing shifts in phenotypic, metabolic characteristics, and structure. However, obesity often results in diminished adipose tissue plasticity. Long non-coding RNA (lncRNA) is a class of RNA defined as being more than 200 nucleotides long and lacking protein-coding capability. With advancements in ribosome profiling, mass spectrometry, and other research technologies, an increasing number of studies have confirmed that short open reading frames (less than 300 nucleotides) within lncRNAs have the capacity to encode functional micropeptides. In our study, we initially identified a biologically active micropeptide, lncRNA Esrp2-as-ORF1(LEAO), encoded by lncRNA Esrp2-as in mice. In diet-induced obesity (DIO)mice, this micropeptide demonstrates the ability to induce fat browning, enhance adipose tissue plasticity, and subsequently improve metabolic homeostasis. Additionally, we observed that the micropeptide LEAO exerts its effects on adipocytes by stimulating IL6 secretion in adipose tissue macrophages. In summary, LEAO may have therapeutic potential for obesity-related metabolic diseases.
Obesity impairs male reproductive development in prepubertal boys via local adipose tissue inflammation and the STAT3/CYP19A1 pathway.
Han W, Lu M, Liu Y … +2 more , Ding Y, Yin C
J Endocrinol Invest · 2026 Jun · PMID 41591733 · Publisher ↗
BACKGROUND: The rising prevalence of childhood obesity is a serious global public health issue and poses a significant threat to male reproductive health. Aromatase (CYP19A1) expression is often elevated in obese men, as...
BACKGROUND: The rising prevalence of childhood obesity is a serious global public health issue and poses a significant threat to male reproductive health. Aromatase (CYP19A1) expression is often elevated in obese men, associated with diminished testosterone levels, but the underlying mechanisms linking childhood obesity to long-term male infertility remain poorly understood. METHODS: We conducted a multi-faceted study combining a cross-sectional clinical investigation, a Mendelian randomization (MR) analysis, bioinformatic analysis of public datasets, and a mechanistic animal study. The clinical study included 30 obese and 30 normal-weight prepubertal boys. Two-sample MR was used to infer the causal relationship between different classes of obesity and male infertility. Gene Expression Omnibus (GEO) datasets were analyzed to identify differentially expressed genes (DEGs) and pathways. A high-fat diet (HFD)-induced obese mouse model was established to validate the bioinformatic hypotheses by investigating the STAT3/CYP19A1 pathway. RESULTS: Clinically, obese boys exhibited significantly smaller testicular volume, shorter penis length, and lower levels of testosterone, LH, Inhibin B, and FSH (P < 0.05). MR analysis revealed a significant causal relationship between childhood obesity (P = 0.038), class 1 obesity (P = 0.0423), and class 2 obesity (P = 0.0041) with male infertility. Bioinformatic analysis of fertility-related datasets implicated CYP19A1 as a key gene, while analysis of adipose tissue datasets highlighted inflammatory pathways. STAT3 was predicted and subsequently confirmed as a key transcription factor linking inflammation to CYP19A1 expression. The HFD-induced obese mouse model recapitulated the human phenotype, showing testicular damage, ectopic lipid deposition, increased apoptosis, and reduced testosterone. Molecularly, we confirmed a significant upregulation of STAT3 and CYP19A1 specifically in the epididymal adipose tissue of obese mice (P < 0.05). CONCLUSION: Our integrated findings suggest that childhood obesity is a causal risk factor for impaired male reproductive function. The mechanism involves a local, paracrine effect of inflamed epididymal adipose tissue, which promotes STAT3-mediated upregulation of CYP19A1, leading to increased local aromatization of androgens and subsequent testicular damage. This STAT3-CYP19A1-testosterone signaling pathway represents a potential therapeutic target for mitigating obesity-related male reproductive disorders.
The association of GNAS defects with pro-inflammatory adipokine levels in pseudohypoparathyroidism type 1.
Dong Y, Yang Y, Song A … +6 more , Jiang Y, Li M, Xia W, Gong F, Wang O, Xing X
J Endocrinol Invest · 2026 Jun · PMID 41591732 · Publisher ↗
PURPOSE: Pseudohypoparathyroidism type 1 (PHP1), caused by GNAS defects, is associated with metabolic syndrome components like obesity and insulin resistance, potentially involving adipokine dysregulation. This study cha...
PURPOSE: Pseudohypoparathyroidism type 1 (PHP1), caused by GNAS defects, is associated with metabolic syndrome components like obesity and insulin resistance, potentially involving adipokine dysregulation. This study characterized serum adipokine profiles in PHP1 and elucidated the independent and interactive effects of GNAS defects and obesity. METHODS: This single-center, cross-sectional study included 60 PHP1 patients with molecularly confirmed GNAS defects (epigenetic or genetic). Controls (n = 60) were matched for body mass index (BMI), age, and sex. Serum adipokines were measured using multiplex enzyme-linked immunosorbent assay. Generalized linear models assessed independent/joint effects of GNAS defects and obesity on adipokines, adjusting for confounders. RESULTS: Overweight/obesity (OW/OB) prevalence was 58.3% among these PHP1 patients, significantly higher in PHP1A (90.9%, n = 11) vs. PHP1B (51.0%, n = 49; P = 0.037). Compared to controls, PHP1 patients exhibited significantly higher monocyte chemoattractant protein-1 (MCP-1) (P = 0.001), resistin (P = 0.001), chemerin (P < 0.001), adipsin (P = 0.007), and advanced glycation end-product receptor (AGER) (P = 0.014), but lower interleukin-8 (IL-8) (P < 0.001). After adjusting for age, sex, OW/OB, calcium, and parathyroid hormone, GNAS defects still independently increased resistin (mean difference [MD] = 0.76 ng/mL, P = 0.034), chemerin (geometric mean ratio [GMR] = 1.15, P = 0.008), and MCP-1 (GMR = 1.21, P = 0.043), but decreased IL-8 (GMR = 0.50, P = 0.004). Within PHP1 patients, resistin was higher in OW/OB individuals vs. non-OW/OB individuals (MD = 1.22 ng/mL, P = 0.005). Interaction analysis showed additive independent effects of GNAS defects and obesity on resistin level (P interaction=0.446). CONCLUSION: GNAS defects are associated with aberrant pro-inflammatory adipokine secretion (resistin, chemerin, MCP-1, IL-8) in PHP1 patients independently of obesity. Obesity appears to amplify metabolic dysregulation, particularly reflected by increased resistin levels. These findings support the importance of early metabolic risk assessment and potential targeted interventions in PHP1.
Prevalence and impact of fibromyalgia on patients with type 2 diabetes: a large-scale real-world data analysis.
Nhu NT, Weng SF, Tseng YH … +1 more , Kang JH
J Endocrinol Invest · 2026 Jun · PMID 41591731 · Publisher ↗
PURPOSE: Fibromyalgia is common in type 2 diabetes (T2D). However, its prevalence and impact on T2D-related complications, particularly in large-scale settings, remain unclear. This study estimated the prevalence of fibr...
PURPOSE: Fibromyalgia is common in type 2 diabetes (T2D). However, its prevalence and impact on T2D-related complications, particularly in large-scale settings, remain unclear. This study estimated the prevalence of fibromyalgia in T2D and its impact on T2D-related complications. METHODS: This retrospective cohort study used TriNetX data. We defined the T2D cohort by using International Classification of Diseases, Tenth Revision codes, and we estimated the prevalence of fibromyalgia in this cohort for the period between June 1, 2019, and June 1, 2024. We defined patients with T2D and fibromyalgia as Cohort 1 and patients with T2D but without fibromyalgia as Cohort 2. We then performed 1:1 propensity score matching between the two cohorts. In July 2024, we conducted risk analyses (measured through odds ratios) and survival analyses by using the built-in algorithms on the TriNetX platform. RESULTS: The overall prevalence of fibromyalgia was 4.03% in patients with T2D (6.16% and 1.65% in women and men, respectively). Patients aged 45–49 and 50–54 years had the highest prevalence of fibromyalgia. Cohort 1 exhibited approximately 20% to 90% higher cumulative odds of T2D-related complications compared with Cohort 2. These complications included cardiovascular disease, major adverse cardiac events, ischemic heart disease, coma, ophthalmic disease, nephropathy, neuropathy, and foot ulcers. Additionally, the instantaneous risk of these complications, with the exception of nephropathy, was higher in Cohort 1 than in Cohort 2. CONCLUSION: This study estimated the prevalence of fibromyalgia in T2D and indicated that fibromyalgia might augment T2D-related complications.
Predictive value of serum CCL18 for recurrence and invasiveness in pituitary neuroendocrine tumors.
Jiao Y, Li G, Chen K … +3 more , Shao C, Yang Z, Zhang G
J Endocrinol Invest · 2026 Jun · PMID 41591730 · Publisher ↗
BACKGROUND: This study aimed to investigate the predictive value of serum CCL18 in the recurrence and invasiveness of pituitary neuroendocrine tumors (PitNETs). CCL18, a chemokine secreted mainly by tumor-associated macr...
BACKGROUND: This study aimed to investigate the predictive value of serum CCL18 in the recurrence and invasiveness of pituitary neuroendocrine tumors (PitNETs). CCL18, a chemokine secreted mainly by tumor-associated macrophages, has been implicated in cancer progression, but its role in PitNETs remains unexplored. METHOD: A total of 463 patients with PitNETs (110 recurrent and 353 non-recurrent) who underwent surgery at Beijing Tiantan Hospital between 2020 and 2022, along with 32 healthy controls, were retrospectively analyzed. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Cat# DCC180). Clinical, radiological, and pathological parameters were assessed, and subgroup analyses were performed according to recurrence and invasiveness. Statistical analyses were conducted using SPSS 26.0, and receiver operating characteristic (ROC) curves were generated with GraphPad Prism 8.0. In addition, CCL18 mRNA expression in recurrence PitNETs and non-recurrence PitNETs tissues was validated by quantitative real-time PCR (qPCR). RESULTS: Serum CCL18 was higher in recurrent than non-recurrent PitNETs (median: 46253 vs. 27834 pg/mL, P < 0.001) and elevated in invasive tumors. ROC analysis showed an AUC of 0.801 (95% CI: 0.752–0.850), with 84.9% sensitivity and 79.2% specificity for recurrence. CCL18 correlated with Knosp grade and Ki-67 index (P < 0.001) and remained an independent predictor in multivariate analysis. qRT-PCR revealed CCL18 mRNA was upregulated in recurrence PitNET tissues versus non-recurrence PitNETs tissues (P < 0.001), suggesting systemic elevation may reflect tumor microenvironment secretion. Recurrent invasive PitNETs had the highest CCL18 levels. CONCLUSIONS: Serum CCL18 is associated with PitNETs recurrence and invasiveness and may serve as a non-invasive biomarker. Combined tissue and serum assessment could improve risk stratification and prognostic evaluation.
Organoid modeling identifies EDN1 as a potential oncogenic driver in papillary thyroid carcinoma via modulation of the Hippo-YAP signaling pathway.
Hai R, Wu F, Tima S … +5 more , Li C, Zhou Y, Yao J, Anuchapreeda S, Zhou X
J Endocrinol Invest · 2026 Mar · PMID 41569405 · Publisher ↗
BACKGROUND: Thyroid carcinoma (TC), particularly papillary thyroid carcinoma (PTC), is the most prevalent endocrine malignancy globally. Endothelin-1 (EDN1) has been implicated in tumor progression in various cancers, bu...
BACKGROUND: Thyroid carcinoma (TC), particularly papillary thyroid carcinoma (PTC), is the most prevalent endocrine malignancy globally. Endothelin-1 (EDN1) has been implicated in tumor progression in various cancers, but its biological role in PTC remains unclear. This study aimed to investigate the expression and function of EDN1 in PTC. METHODS: EDN1 expression in PTC cells and tissues was assessed using RT-qPCR and immunofluorescence. Lentiviral knockdown of EDN1 was performed in PTC cells and organoids. Cell proliferation and migration were evaluated via CCK-8, colony formation, and Transwell assays. The effects of EDN1 inhibition were further examined in PTC organoid and murine xenograft models. Western blotting (WB) and immunofluorescence were used to analyze the expression of proliferation-related (PCNA), migration-related (MMP2), and Hippo-YAP signaling proteins. RESULTS: EDN1 was highly expressed in PTC cells and tissues. Its knockdown significantly suppressed PTC cell proliferation, migration, and tumor growth in xenografts. Additionally, EDN1 deficiency reduced organoid formation efficiency and size. Mechanistically, EDN1 exerted its oncogenic effects partly through the Hippo-YAP pathway. CONCLUSION: Our research findings suggest that EDN1, at least partially through the Hippo-YAP signaling pathway, may exist as a potential oncogenic driver in PTC, suggesting its potential as a diagnostic and therapeutic biomarker for PTC.
Digital tomosynthesis derived textural and geometric measures of vertebral bone quality in postmenopausal women with primary hyperparathyroidism.
Yeni YN, Oravec DJ, Yadav RN … +5 more , Drost J, Warner E, Flynn MJ, Divine GW, Rao SD
J Endocrinol Invest · 2026 Apr · PMID 41553411 · Publisher ↗
PURPOSE: Risk of vertebral fractures is increased in primary hyperparathyroidism (PHPT). Bone qualities affected by PHPT are not necessarily reflected in bone mineral density (BMD), requiring imaging modalities with capa...
PURPOSE: Risk of vertebral fractures is increased in primary hyperparathyroidism (PHPT). Bone qualities affected by PHPT are not necessarily reflected in bone mineral density (BMD), requiring imaging modalities with capability to capture bone microstructure and geometry. Digital tomosynthesis (DTS) imaging is a method with such capability. Therefore, the objectives of this study were to determine (i) vertebral bone quality differences between women who have established PHPT and normal controls using DTS, and (ii) the extent to which DTS discriminates patients with PHPT from those without. METHODS: 50 postmenopausal women with established PHPT and 54 control women without PHPT (nPHPT) were DXA imaged to measure spine BMD and trabecular bone score (TBS). They were then DTS imaged to measure vertebral width and area as well as the textural properties of vertebral bone: Degree of anisotropy (DA), fractal dimension (FD), lacunarity (λ), scale-dependent lacunarity (S) and line fraction deviation (LFD). RESULTS: FD was significantly higher while λ and LFD were significantly lower in the PHPT group than in the nPHPT group. λ was a significant predictor of PHPT status, independently from race, BMD and TBS, raising the overall AUC to 0.805. We observed a dichotomy between the races; larger vertebral area in White patients, but smaller vertebral area in Black patients, was associated with PHPT independently from BMD or TBS. CONCLUSION: DTS derived vertebral size and textural properties differ between PHPT and nPHPT, discriminate PHPT status independently from DXA, and therefore may be useful in the assessment of bone quality in PHPT.
Elevated uric acid levels link to a higher cardiometabolic risk profile in adolescents.
de Quadros Iorra F, Rodrigues PG, Barcelos AT … +2 more , Cureau FV, Schaan BD
J Endocrinol Invest · 2026 May · PMID 41543681 · Publisher ↗
BACKGROUND: Serum uric acid (sUA) plays a complex role in cardiovascular disease (CVD). However, its utility as an early cardiometabolic risk marker in adolescents remains underexplored. PURPOSE: To examine the relations...
BACKGROUND: Serum uric acid (sUA) plays a complex role in cardiovascular disease (CVD). However, its utility as an early cardiometabolic risk marker in adolescents remains underexplored. PURPOSE: To examine the relationship between sUA levels and CVD risk factors, and to assess its potential in identifying metabolically unhealthy adolescents across different weight categories. METHODS: This is a cross-sectional analysis with 4,390 adolescents aged 12 to 17 years from four Brazilian cities. sUA was categorized into quartiles. Linear regression, adjusted for confounders, assessed associations between sUA quartiles and cardiometabolic variables. Adjusted Poisson regression with robust variance estimated prevalence ratios (PR) of metabolic syndrome components across sUA quartiles, as well as the PR of a metabolically unhealthy profile, stratified by weight categories. RESULTS: The sample was predominantly female (61.5%). The mean (SD) age was 14.8 (1.5) years, and median (IQR) sUA was 4.5 (3.8, 5.4) mg/dL. Higher sUA quartiles were associated with increased waist circumference, BMI Z-score, elevated blood pressure, higher triglycerides, and higher total and LDL cholesterol. There was also a negative association with HDL cholesterol and adiponectin. An inverse sUA-fasting plasma glucose association was also observed. Adolescents in the highest sUA quartile showed substantially higher PR for metabolic syndrome and its components (high waist circumference, high blood pressure, low HDL cholesterol, high triglycerides). The PR of metabolically unhealthy profile progressively increased across sUA quartiles, in both normal-weight individuals (PR 1.29, 95% CI 1.14-1.45, in the fourth sUA quartile) and, even more substantially, in those with overweight/obesity (PR 1.87, 95% CI 1.67-2.08, in the fourth sUA quartile). CONCLUSION: Higher sUA levels were strongly associated with a worse cardiometabolic profile and an increased prevalence of metabolic unhealthiness, thereby reinforcing the role of sUA as an early risk marker in adolescence.
Associations of long-term waist circumference trajectories with the risk of fragility fractures: a prospective cohort study.
Guo L, Chen S, Zhang N … +8 more , Tang R, Yao W, Wei S, Hou X, Xing L, Zhang L, Wu S, Tian F
J Endocrinol Invest · 2026 May · PMID 41543680 · Publisher ↗
OBJECTIVES: The relationship between the patterns of WC trajectory and fragility fracture in the Chinese population remains unclear. This prospective study investigated the effect of long-term WC trajectory on fragility...
OBJECTIVES: The relationship between the patterns of WC trajectory and fragility fracture in the Chinese population remains unclear. This prospective study investigated the effect of long-term WC trajectory on fragility fracture based on community-based cohort. METHODS: This prospective study was conducted based on the Kailuan Study and included a total of 47,288 participants (mean age, 56.7 years) free of fragility fracture and with repeated measurements of WC from 2006 to 2014. The WC trajectories (2006-2014) were modeled by group-based trajectory modeling (GBTM), and three trajectories were identified: low-stable group (n = 12,546), medium-stable group (n = 28,532), and high-stable group (n = 6,210). The association between WC trajectories and incident fragility fractures was assessed using Cox proportional hazards models, with stratified analyses and interaction tests conducted by sex (male/female) and age (≤ 65 years / > 65 years). RESULTS: During an average follow-up of 8.31 years, 663 participants developed fragility fractures. After adjusting for potential confounding factors, compared with those in the low-stable group, the hazard ratio (HR) and 95% confidence interval (CI) for incident fragility fracture in the medium-stable group and high-stable group were 1.25 (1.01-1.54) and 1.55 (1.12-2.14), respectively. In Individuals aged ≤ 65 years, the medium group and high-stable group had a 35% (HR = 1.35, 95% CI: 1.03-1.77) and 98% (HR = 1.98, 95% CI: 1.32-2.97) higher fracture risk, respectively. CONCLUSIONS: WC trajectories were significantly associated with the risk of fragility fracture, and the association was more evident in aged ≤ 65 years population.
Caloric restriction attenuates oxidative and inflammatory markers of aging, while compromising germinative epithelium homeostasis in the rat aged testis.
Bossio S, La Russa D, Antonucci G … +9 more , Lofaro D, Urlandini L, Mandalà M, Conforti F, Di Dio M, Aversa A, Rago V, Di Agostino S, Perri A
J Endocrinol Invest · 2026 May · PMID 41511748 · Publisher ↗
PURPOSE: Aging is accompanied by a chronic low-grade systemic inflammatory state known as "inflammaging", driven by the accumulation of pro-inflammatory and immunosenescent cells, oxidative stress, and dysregulation of a...
PURPOSE: Aging is accompanied by a chronic low-grade systemic inflammatory state known as "inflammaging", driven by the accumulation of pro-inflammatory and immunosenescent cells, oxidative stress, and dysregulation of apoptosis and autophagy. Experimental evidence suggests that caloric restriction (CR) can slow down inflammaging, although its impact on spermatogenesis remains controversial. This study aimed to investigate the effects of CR on age-related testicular inflammation and any effects on germ cells. METHODS: Fourteen 18-month-old Sprague-Dawley rats were randomly divided into two groups and sacrificed after 6 months: 7 rats on a normal ad libitum diet (ND) and 7 rats on CR (40% reduction in caloric intake). Western blot (WB) and immunohistochemical (IHC) analyses were performed to assess the expression of key markers of inflammation, oxidative stress, apoptosis, and autophagy, alongside morphological evaluations. RESULTS: IHC analysis reveals that CR disrupts germinative epithelium and somatic cells, and reduces the expression of Ob-R, GLP-1R, GPX4, NOX4, and SIRT1. WB analysis showed that CR lowered COX2 expression, through downregulation of the NFκB/MAPK pathway, decreased the expression of NLRP3 inflammasome, Caspase-1, and pro-inflammatory cytokine IL1-β, and restored redox homeostasis. Consistently, IHC highlighted a marked reduction in proinflammatory immune cell infiltration in the testis of CR rats. Moreover, as a consequence of the germ cells number reduction CR-induced, we observed a decreased expression of p75NTR and its pro-apoptotic signaling components (pJNK, p53, and BAX), while concurrently downregulating p62/SQSTM1 expression. CONCLUSIONS: Our findings highlight the dual impact of CR on testicular aging, on the one hand the significant attenuation of oxi-inflammation, on the other hand the impairment of germinal epithelial physiology. These results underscore the need for further studies to define optimal timing and duration of dietary interventions aimed at mitigating age-related decline in male reproductive function.
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