J. Endocrinol. Invest. [JOURNAL]
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200 papers
Long-term endocrine and testicular outcomes in male survivors of childhood acute lymphoblastic leukemia.
Karakaş H, Tarçın G, Bayramoğlu E … +6 more , Turan H, Ocak S, Evliyaoğlu O, Celkan T, Apak H, Ercan O
J Endocrinol Invest · 2026 Mar · PMID 41511747 · Publisher ↗
BACKGROUND AND AIM: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for long-term endocrine and gonadal dysfunction. While several studies have explored these risks in heterogeneous cancer survivor...
BACKGROUND AND AIM: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for long-term endocrine and gonadal dysfunction. While several studies have explored these risks in heterogeneous cancer survivor groups, data specific to ALL survivors remain limited. Herein, we aimed to evaluate late endocrine and gonadal effects in a homogeneous cohort of male childhood ALL survivors classified by risk groups, and to assess the predictive value of serum follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels for semen analysis outcomes. METHODS: This cohort study included male survivors of childhood ALL treated between 2000 and 2020, classified as standard, intermediate, or high risk. Endocrine parameters, reproductive hormones, and semen analyses were evaluated. RESULTS: Fifty-four survivors (mean age 17.5 ± 5.9 years) were included. Endocrine disorders were present in 40.7%, with obesity in 9.4%. Semen analysis (n = 33) revealed abnormal findings in 42.4% and azoospermia in 24.2%. The prevalence of gonadal dysfunction increased progressively from standard to high-risk groups. FSH thresholds of 3.55 mIU/mL was predictive of abnormal semen parameters (AUC: 0.88). AMH showed no predictive value for semen outcomes. CONCLUSIONS: This is the first study to evaluate gonadal outcomes through semen analysis in a homogeneous cohort of childhood ALL survivors stratified by risk group. Our findings support the use of FSH as a predictive marker of impaired spermatogenesis, while AMH appears to have no predictive value. The study also highlights the need for early reproductive counseling and consideration of fertility preservation strategies, especially in high-risk patients.
Diabetes does not modify the renal-protective effect of intravenous amino acids infusion after cardiac surgery.
Consonni M, Fresilli S, Kotani Y … +30 more , Garofalo E, Bradic N, Scandroglio AM, Ti LK, Comis M, Oriani A, Pisano A, Belletti A, Guarracino F, Losiggio R, Redaelli MB, Pontillo D, Arangino C, Pruna A, Federici F, D'Amico F, Silvetti S, Labanca R, Ferrod F, Pittella G, Corbo F, Ranucci M, Cortegiani A, Paternoster G, Bove T, Longhini F, Monaco F, Zangrillo A, Piemonti L, PROTECTION Study Group Collaborators
J Endocrinol Invest · 2026 May · PMID 41511746 · Publisher ↗
PURPOSE: Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased morbidity and mortality. Intravenous amino acids (AA) infusion reduces postoperative AKI. Given the high...
PURPOSE: Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased morbidity and mortality. Intravenous amino acids (AA) infusion reduces postoperative AKI. Given the high prevalence of patients with diabetes and their increased susceptibility to renal injury, this study aimed to assess whether the renal-protective effect of AA infusion is maintained in this population. METHODS: This post-hoc subgroup analysis examined patients with diabetes included in the multinational, double-blind, randomized, placebo-controlled PROTECTION trial. Participants were randomized to receive a continuous intravenous infusion of AA (2 g/kg of the ideal body weight per day; up to 72 h) or placebo during the perioperative period of cardiac surgery. RESULTS: Among 644 patients with diabetes (AA n = 309; placebo n = 335), the incidence of any-stage AKI was 43.3% in the AA group versus 47.8% in the placebo group, with no significant interaction observed compared to patients without diabetes (interaction p = 0.82). Similarly, stage 3 AKI occurred in 2.3% of patients in AA group versus 4.8% in the placebo group, with no interaction detected (interaction p = 0.65). CONCLUSION: The beneficial effect of perioperative AA infusion has similar magnitude and direction among patients with or without diabetes. These findings support the use of AA infusion as a renal-protective strategy for all patients undergoing cardiac surgery. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03709264 – registered on October 17th, 2018.
Skeletal muscle expression of the genes associated with glycoprotein 130 signaling in relation to obesity and insulin sensitivity.
Danowska M, Nikołajuk A, Strączkowski M
J Endocrinol Invest · 2026 Apr · PMID 41505054 · Full text
PURPOSE: Glycoprotein 130 (gp130) is a critical signal transducer in the interleukin-6 (IL-6) receptor family, regulates immune response, inflammation, and metabolic processes. In obesity, elevated levels of proinflammat...
PURPOSE: Glycoprotein 130 (gp130) is a critical signal transducer in the interleukin-6 (IL-6) receptor family, regulates immune response, inflammation, and metabolic processes. In obesity, elevated levels of proinflammatory cytokines like IL-6 can lead to chronic activation of gp130, disrupting normal signaling in tissues such as skeletal muscle. The aim of the study was to investigate the expression of IL-6–related and JAK/STAT pathway genes in human skeletal muscle and to explore their association with insulin sensitivity, as well as to evaluate the role of serum soluble gp130 (sgp130) in the development of overweight and obesity. METHODS: The study included 57 participants, 25 with normal body weight (control group), 17 with overweight and 15 with obesity. Hyperinsulinemic-euglycemic clamp and muscle biopsy were conducted. Muscle mRNA expression was analysed by qPCR. RESULTS: Individuals with overweight exhibited significantly lower IL6R expression in skeletal muscle, while those with obesity showed reduced IL6ST expression. The expression levels of IL6R (r = 0.28, p = 0.036), IL6ST (r = 0.46, p < 0.001), JAK2 (r = 0.32, p = 0.015), and STAT3 (r = 0.44, p < 0.001) and PRKAA2 (r = 0.26, p = 0.049) in skeletal muscle were positively correlated with insulin sensitivity. Additionally, individuals with overweight and obesity had significantly higher serum sgp130 levels. Serum sgp130 was positively correlated with BMI (r = 0.43, P < 0.01) and inversely associated with insulin sensitivity (r = -0.44, P < 0.01). CONCLUSION: Gp130 is associated with insulin sensitivity in skeletal muscle in obesity, revealing a novel mechanism linking gp130 to metabolic regulation.
Oral health and salivary inflammatory markers in children and adolescents with type 1 diabetes: A cross-sectional study.
Catamo E, Tornese G, Navarra C … +5 more , Aldegheri L, Zanotta N, Comar M, Cadenaro M, Robino A
J Endocrinol Invest · 2026 Jun · PMID 41505053 · Full text
PURPOSE: To evaluate the oral health status of children and young adults with type 1 diabetes (T1D) compared with healthy controls (HC), and its association with clinical parameters and salivary inflammatory markers. MET...
PURPOSE: To evaluate the oral health status of children and young adults with type 1 diabetes (T1D) compared with healthy controls (HC), and its association with clinical parameters and salivary inflammatory markers. METHODS: Seventy-two subjects with T1D and 86 HCs underwent a clinical oral examination. Salivary cytokines were measured using multiplex immunoassays. Differences between oral conditions, clinical parameters and cytokines were tested and mediation models were used to evaluate the role of T1D and HbA1c. RESULTS: T1D subjects showed significantly higher frequencies of caries (67% vs. 28.5%) and gingivitis (76% vs. 42%) compared with HC (p < 0.001), independently by oral hygiene habits. In T1D, the presence of caries and gingivitis is associated with unfavourable clinical outcomes, including higher HbA1c, triglycerides, and urinary creatinine (p-value < 0.05). Salivary cytokine profile differed according to oral condition: caries was associated with reduced IL-4, IL-10, and IFN-γ; gingivitis with elevated IL-1Ra and RANTES; and both conditions with increased IL-1β (p-value < 0.05). Mediation analyses revealed no significant influence of HbA1c. CONCLUSION: Children and young adults with T1D show a higher prevalence of oral diseases and distinct inflammatory profile, regardless of metabolic status. These findings call for routine integration of oral assessment in T1D management.
Achille beltrame: an exceptional wedding procession.
de Herder WW
J Endocrinol Invest · 2026 Jan · PMID 41505052 · Publisher ↗
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Amputation and gangrene associated with SGLT2 inhibitors: pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database.
Ajabnoor AM
J Endocrinol Invest · 2026 Jun · PMID 41505051 · Full text
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed to diabetic patients for their cardiorenal benefits. However, concerns over adverse events—specifically amputation risk and gangrene—ha...
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed to diabetic patients for their cardiorenal benefits. However, concerns over adverse events—specifically amputation risk and gangrene—have risen in recent years. This study aimed to describe the frequency and severity of these events in relation to SGLT2 inhibitor use, using the U.S. FDA Adverse Event Reporting System (FAERS). METHODS: OpenVigil 2.1 was used to extract safety reports submitted to FAERS from 2003 Q4 to 2024 Q4. Amputation and gangrene events linked to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) were identified and compared to other drugs. Reporting odds ratios (RORs) were calculated. RESULTS: A total of 3,540 adverse event reports were identified: 2,128 for canagliflozin, 361 for dapagliflozin, 1,049 for empagliflozin, and 2 for ertugliflozin. Canagliflozin was strongly associated with toe amputation (ROR = 635.6; 95%CI: 566.7–712.1), foot amputation (ROR = 201.8; 95%CI: 174.3–233.7), and Fournier’s gangrene (ROR = 117.5; 95%CI: 100.0–138.0). Empagliflozin was linked with Fournier’s gangrene (ROR = 565.2; 95%CI: 525.3–608.2) and toe amputation (ROR = 21.2; 95%CI: 17.6–25.6). Dapagliflozin showed weaker signals; ertugliflozin had minimal data. CONCLUSION: Toe amputation and Fournier’s gangrene were most reported with canagliflozin and empagliflozin, reinforcing prior safety concerns and the need for monitoring.
A positive corticotropin-releasing hormone test may obviate the need for petrosal sinus sampling in patients with cushing's disease.
Losa M, Loli P, Nocera G … +1 more , Mortini P
J Endocrinol Invest · 2026 May · PMID 41493525 · Publisher ↗
PURPOSE: Bilateral inferior petrosal sinus sampling (BIPSS) is considered the most accurate procedure to confirm the diagnosis of Cushing's disease (CD). However, it is a cumbersome and costly procedure. We aim to determ...
PURPOSE: Bilateral inferior petrosal sinus sampling (BIPSS) is considered the most accurate procedure to confirm the diagnosis of Cushing's disease (CD). However, it is a cumbersome and costly procedure. We aim to determine whether the corticotropin-releasing hormone (CRH) test alone might differentiate CD from ectopic adrenocorticotropin (ACTH) syndrome (EAS). METHODS: In this retrospective, observational study we investigated 523 consecutive patients with ACTH-dependent hypercortisolism: 502 with CD and 21 with EAS. All patients underwent a CRH test and surgery for the removal of the ACTH-secreting tumor. Two hundred patients with CD and 17 with EAS underwent BIPSS. The diagnostic CRH test performance included sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). RESULTS: using a 50% ACTH increase as the threshold, the CRH test correctly classified 438 cases of CD (87%) and 20 cases of EAS (95%). The diagnostic metrics were as follows: SE 87%, SP 95%, PPV 99%, NPV 23%, accuracy 92%, PLR 18.35, and NLR 0.05. BIPSS correctly diagnosed all cases of EAS (100%) and 188 cases of CD (94%). CONCLUSIONS: Our study shows that a positive CRH test reliably differentiates CD from EAS and obviates the need for BIPSS. The performance of CRH test is similar in patients with and without a visible pituitary microadenoma or a microadenoma < 6 mm. Accepting the very low probability of EAS in a patient with positive ACTH response to CRH, we can propose pituitary surgery without performing BIPSS.
Obstructive sleep apnea is more closely associated with bilateral primary aldosteronism than unilateral primary aldosteronism.
He W, Zan L, Sun Y … +8 more , Tang Z, Feng Z, Song Y, Cheng Q, Hu J, Li Q, Mei M, Chongqing Primary Aldosteronism Study (CONPASS) Group
J Endocrinol Invest · 2026 Feb · PMID 41493524 · Publisher ↗
CONTEXT: Obstructive Sleep Apnea (OSA) has been implicated in the pathophysiology of primary aldosteronism (PA), yet its specific relationship with bilateral primary aldosteronism (BPA) remains unclear. Clarifying this a...
CONTEXT: Obstructive Sleep Apnea (OSA) has been implicated in the pathophysiology of primary aldosteronism (PA), yet its specific relationship with bilateral primary aldosteronism (BPA) remains unclear. Clarifying this association is essential for optimizing diagnostic and therapeutic strategies. OBJECTIVE: To investigate the independent association between OSA and BPA, and compare clinical and sleep parameters between unilateral primary aldosteronism (UPA) and BPA. METHODS: In this single-center cross-sectional cohort study, a total of 136 PA patients (79 UPA, 57 BPA) underwent comprehensive clinical, biochemical, and polysomnographic evaluations. Prevalence and severity of OSA were compared between groups. Logistic regression analyses, both crude and adjusted, assessed the independent association between OSA and BPA. RESULTS: Compared to UPA, BPA patients exhibited significantly higher body weight, BMI, waist circumference, triglycerides, serum potassium, and baseline plasma renin concentration, but lower 24-hour urinary potassium, and plasma aldosterone concentrations (all P < 0.05). Patients with BPA demonstrated higher apnea-hypopnea index (AHI) [21.5(3,32.2) vs. 14.0(10.9,52.7), P = 0.008], higher obstructive apnea counts and lower the lowest oxygen saturation during sleep. Moderate-to-severe OSA prevalence was greater in BPA than UPA (61% vs. 48%; P = 0.004). Among patients with OSA, BPA prevalence significantly exceeded UPA (91% vs. 66%; P = 0.001). OSA patients also had higher BPA prevalence compared to non-OSA patients (50% vs. 16%; P = 0.001). Logistic regression revealed an independent association between OSA and BPA in both crude (OR 5.400, 95% CI 1.930-15.107; P = 0.001) and adjusted analyses (OR 9.91, 95% CI 1.19-82.67; P = 0.034). CONCLUSION: OSA is significantly associated with increased BPA risk, exhibiting higher prevalence and severity in BPA patients compared to UPA. Our findings underscore the importance of routine OSA screening in PA patients, especially those with BPA, to improve outcomes and reduce cardiovascular risk.
A poor man of short stature: a not immediate etiological iconodiagnosis.
Trimarchi F, Martino E, Bartalena L
J Endocrinol Invest · 2026 Jan · PMID 41493523 · Publisher ↗
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Effect on insulin clearance of different pharmacological treatments in women with polycystic ovary syndrome: a hypothesis-generative study.
Tosi F, Zanolin ME, Garofalo S … +3 more , Gremes V, Zoppini G, Moghetti P
J Endocrinol Invest · 2026 May · PMID 41489804 · Publisher ↗
PURPOSE: Impaired insulin clearance has been found in women with PCOS and contribute to generate hyperinsulinemia in these subjects. However, the mechanisms underlying this phenomenon remain unknown. The aim of this retr...
PURPOSE: Impaired insulin clearance has been found in women with PCOS and contribute to generate hyperinsulinemia in these subjects. However, the mechanisms underlying this phenomenon remain unknown. The aim of this retrospective study was to explore if the heterogeneous treatments used in these patients to counteract their hormonal and metabolic alterations can also affect insulin clearance. METHODS: Forty-seven women with PCOS were included in the study. They belonged to different experimental groups, submitted to treatments with the following drugs: GnRH-agonist (buserelin, n = 10), antiandrogens (spironolactone, n = 9), metformin (n = 18), or placebo (n = 10). Metabolic clearance rate of insulin (MCRI) and insulin sensitivity were measured by the hyperinsulinemic euglycemic clamp, performed before and after treatment. Insulin secretion was estimated by the HOMA β-index. RESULTS: Treatments were associated, as expected, with different clinical effects. In ANOVA analysis, changes in MCRI significantly differed between treatment groups. In particular, metformin increased MCRI as compared with other treatments or placebo. Mediation analysis showed that about 25% of this effect of metformin was mediated by the concurrent BMI change, whereas it was not influenced by changes in peripheral insulin sensitivity or insulin secretion. CONCLUSION: The impairment of MCRI, which contributes to the hyperinsulinemia typical of PCOS, significantly improved after treatment with metformin. This effect was only partially explained by the reduction of BMI, whereas changes in insulin sensitivity did not show a mediation effect in this phenomenon, suggesting that other metformin-induced mechanisms are involved.
Comparing the therapeutic efficacy of radiofrequency vs. Microwave ablation for non-functioning benign thyroid nodules.
Teliti M, Chytiris S, Fonte R … +6 more , Croce L, Businaro LL, Marchiselli Dell' Innocenti SA, Coperchini F, Magri F, Rotondi M
J Endocrinol Invest · 2026 Feb · PMID 41489803 · Full text
PURPOSE: The aim of the study was to compare the efficacy, procedural features, and safety profile of radiofrequency ablation (RFA) versus microwave ablation (MWA) for the treatment of non-functioning benign thyroid nodu...
PURPOSE: The aim of the study was to compare the efficacy, procedural features, and safety profile of radiofrequency ablation (RFA) versus microwave ablation (MWA) for the treatment of non-functioning benign thyroid nodules (BTNs). METHODS: This retrospective, single-centre, cohort study included 203 nodules treated with RFA and 71 with MWA by a single experienced operator. Multivariate linear regression analysis was performed to identify independent predictors of treatment response, defined as 12-month volume reduction rate (VRR). Complication rates were also compared between RFA and MWA. A 1:1 case-control matching was performed based on baseline nodule volume and composition, yielding two matched cohorts of 66 patients each. VRRs after 6 and 12 months were compared between two groups. RESULTS: In the overall population, similar VRRs were observed after 6 and 12 months. Significant differences in baseline nodule volume (24.35 ± 17.15 ml vs. 17.25 ± 15.22ml; p = 0.001) and in procedure times (519.96 ± 289.45s vs. 649.61 ± 321.05s; p = 0.003) were found for MWA and RFA, respectively. Multivariate analysis identified baseline volume (p < 0.001) and composition (p < 0.033) as significant and independent predictors of VRR. Both techniques showed comparable safety. In the matched cohorts, VRRs after 6-months were similar, while a higher VRR after 12-months was observed for MWA compared to RFA (64.70 ± 13.89% vs. 58.71 ± 16.81%; p = 0.028). CONCLUSION: RFA and MWA are both safe and effective for treating BTNs. In the overall population, VRRs were similar between RFA and MWA, with MWA requiring shorter procedure times. After matching for key predictors of therapeutic response, MWA demonstrated superior efficacy at 12-months.
Oxidized metabolites of linoleic acid as biomarkers of pancreatic beta-cell function in the first-onset type 2 diabetic patients with obesity.
Ge X, Wang J, Du J … +7 more , Li W, Xi L, Jiang X, Peng W, Wang X, Guo X, Huang S
J Endocrinol Invest · 2026 May · PMID 41489802 · Publisher ↗
OBJECTIVES: The role of oxylipins in type 2 diabetes (T2D) with obesity remains poorly understood. This study aimed to characterize oxylipin profiles in T2D patients with obesity, identify associations with pancreatic be...
OBJECTIVES: The role of oxylipins in type 2 diabetes (T2D) with obesity remains poorly understood. This study aimed to characterize oxylipin profiles in T2D patients with obesity, identify associations with pancreatic beta-cell function, and suggest potential therapeutic targets. METHODS: We recruited first-onset T2D patients with obesity (OB group, n = 15) and normal-weight T2D patients (NW group, n = 15), matched by gender, age, and blood lipid levels. Serum samples were collected in a fasting state before medication. Oxylipin profiling was analyzed using liquid chromatography-tandem mass spectrometry, detecting 120 oxylipins. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze oxylipin profiles, and Pearson’s correlation coefficients assessed the relationship between oxylipin concentrations and clinical parameters. RESULTS: Six oxylipins with variable importance in projection (VIP > 1) and p < 0.05 were significantly different between OB and NW groups. Five oxylipins (13-oxoODE, 12,13-EpOME, 15-keto-PGE2, 9,10-EpOME, 16(17)-EpDPE) were elevated in the OB group, while 2,3-dinor-8-iso-PGF2α was reduced. Correlation analysis revealed that 13-oxoODE, 15-keto-PGE2, and 16(17)-EpDPE levels positively correlated with BMI, visceral adipose tissue (VAT), and pancreatic beta-cell function. CONCLUSIONS: Oxylipin profiling in first-onset T2D patients with obesity revealed that altered oxylipin metabolism, particularly linoleic acid pathways, is closely linked to pancreatic beta-cell dysfunction. These findings suggest potential biomarkers for therapeutic intervention.
History before diagnosis in adult-onset craniopharyngioma: associations with initial presentation and long-term prognosis: a retrospective cohort study of 151 patients.
Wu J, Liang F, Ye Z … +8 more , Pan L, Wu B, Wu X, Luo H, Xie S, Tang B, Xu C, Hong T
J Endocrinol Invest · 2026 Apr · PMID 41489801 · Publisher ↗
PURPOSE: Adult-onset craniopharyngiomas (CPs) often present after diagnostic delays, yet the prognostic relevance of duration of history (DOH) and specific clinical manifestations remains unexplored. METHOD: Data of pati...
PURPOSE: Adult-onset craniopharyngiomas (CPs) often present after diagnostic delays, yet the prognostic relevance of duration of history (DOH) and specific clinical manifestations remains unexplored. METHOD: Data of patients aged > 18 years at CP diagnosis between June 2012 and October 2024 at the First Affiliated Hospital of Nanchang University were retrospectively reviewed. Associations between DOH, specific symptoms, and tumor characteristics at diagnosis, as well as long-term outcomes, were systematically analyzed. RESULTS: Among 151 patients (median follow-up, 71 months) in our cohort, the median DOH was 5 months and showed no significant correlation with tumor volume at diagnosis, hypothalamic involvement, extent of resection, or long-term prognosis including mortality, recurrence, and hypothalamic syndrome at last visit. Patients with amenorrhea/sexual dysfunction in history demonstrated significantly longer DOH (p < 0.001), while those with neurological deficits (p = 0.043) or hydrocephalus (p = 0.044) were associated with shorter DOH. Neurological deficits in history was associated with larger tumor volume at diagnosis (p = 0.016). Headache presented as the first symptom was linked to significantly shorter DOH (p = 0.003) and neurological deficits as the first symptom was associated with worse progression-free survival (p = 0.047). CONCLUSION: Diagnostic delays are common in adult-onset CP patients but appear unrelated to tumor burden or long-term prognosis. Neurological deficits in history or as the first symptom should trigger prompt diagnostic workup and more rigorous follow-up, while prolonged diagnostic delays in those with endocrine symptoms underscore the need for heightened awareness among clinicians to expedite referral and diagnosis.
Reliability of extraocular muscle biomechanics in the evaluation of disease activity in thyroid eye disease.
Li H, Huo Y, Wu B … +6 more , Zhang N, Zhao Y, Cao Y, Ren M, Zhao H, Wang Y
J Endocrinol Invest · 2026 Apr · PMID 41484410 · Publisher ↗
PURPOSE: To evaluate extraocular muscle (EOM) stiffness in the identification of different stages of thyroid eye disease (TED) and to explore its associations with magnetic resonance imaging parameters. METHODS: This ret...
PURPOSE: To evaluate extraocular muscle (EOM) stiffness in the identification of different stages of thyroid eye disease (TED) and to explore its associations with magnetic resonance imaging parameters. METHODS: This retrospective cross-sectional study included 58 participants (19 with active TED, 21 with inactive TED, and 18 controls) and used real-time elastography and magnetic resonance imaging to determine the elastic ratio, native T1 value, and extracellular volume (ECV) fraction of EOMs. Correlation analysis of these parameters was performed, and receiver operating characteristic curves (ROC) were generated to assess their ability to evaluate TED clinical activity. RESULTS: Compared with controls, the elastic ratio of the medial rectus (MR) muscles was significantly higher in patients with inactive TED and significantly lower in those with active TED (P < 0.05). The elastic ratio and mean ECV fraction were strongly correlated in the MR muscles (r = 0.91) and moderately correlated in the lateral rectus muscles (r = 0.72). The are a under the ROC (AUROC) for the elastic ratio (AUROC = 0.919) was higher than that for the mean ECV fraction (AUROC = 0.847) in the MR muscles; however, both showed a comparable ability to diagnose inactive TED (P = 0.13). The optimal cutoff value of the elastic ratio in MR muscles was 6.4, which detected inactive TED with a specificity of 76.2% and sensitivity of 89.5%. CONCLUSION: The EOM elastic ratio increased with the progression of TED from the active to the inactive phase, and is a useful clinical marker of EOM fibrosis. Our study provides novel evidence for the easier and noninvasive clinical assessment of TED activity via the detection of EOM fibrosis using biomechanics.
Therapeutic potential of adipose-derived stem cells for noncommunicable diseases.
Palma G, Gioia LD, Tedesco C … +5 more , Cignarelli A, Natalicchio A, Laviola L, Giorgino F, Perrini S
J Endocrinol Invest · 2026 May · PMID 41484409 · Publisher ↗
PURPOSE: The progressive increase in life expectancy has been accompanied by a growing burden of chronic degenerative noncommunicable diseases (NCDs), with major consequences for quality of life and healthcare systems. T...
PURPOSE: The progressive increase in life expectancy has been accompanied by a growing burden of chronic degenerative noncommunicable diseases (NCDs), with major consequences for quality of life and healthcare systems. This scenario underscores the need for innovative therapeutic strategies aimed at preserving organ function and metabolic homeostasis. Adipose-derived stem/stromal cells (ASCs) have emerged as a promising tool in regenerative medicine due to their multipotency, immunomodulatory properties, and paracrine activity. METHODS: We reviewed available preclinical and clinical evidence supporting the therapeutic potential of ASCs in chronic noncommunicable diseases. The analysis focused on ASC biology, mechanisms of action, and current clinical applications, with particular attention to metabolic and endocrine disorders, while also considering cardiovascular, musculoskeletal, neurodegenerative, and other chronic degenerative conditions. RESULTS: Preclinical and clinical studies indicate that ASCs may contribute to tissue repair and functional recovery through differentiation capacity and paracrine signaling, including anti-inflammatory, angiogenic, and cytoprotective effects. In metabolic and endocrine diseases, ASCs have shown potential to improve insulin sensitivity, support pancreatic function, and mitigate chronic metabolic complications. Additional therapeutic applications have been explored in osteoarthritis, cardiovascular disease, neurodegenerative disorders, chronic intestinal and liver diseases, and age-related tissue degeneration, although the strength of clinical evidence varies across indications. CONCLUSIONS: ASCs represent a promising regenerative strategy for chronic degenerative NCDs, particularly in the metabolic and endocrine setting. However, clinical translation remains limited by heterogeneous evidence, regulatory challenges, and the need for standardized protocols and well-designed clinical trials.
Too late, too often: missed opportunities in male bone health: a real-world portrait from a 14-year specialist referral experience.
De Vincentis S, Russo A, Taliani E … +6 more , Ansaloni A, Domenici D, D'Angelo G, Demichelis V, Madeo B, Rochira V
J Endocrinol Invest · 2026 Mar · PMID 41460455 · Full text
PURPOSE: To characterize, using real-life data, the clinical profile of men undergoing their first bone health evaluation at a tertiary academic center over a 14-year period. METHODS: Retrospective, observational, cross-...
PURPOSE: To characterize, using real-life data, the clinical profile of men undergoing their first bone health evaluation at a tertiary academic center over a 14-year period. METHODS: Retrospective, observational, cross-sectional study including adult men referred to our center between 2007 and 2021 for bone health assessment. Fractures, comorbidities, risk factors for bone loss, and pharmacological treatments were collected. RESULTS: 536 men were enrolled (147 under 50, 385 over 50). At least one comorbidity associated with bone loss was found in 49.3% of patients, and 43.8% were receiving medications causing bone mineral density (BMD) reduction-mainly corticosteroids and androgen deprivation therapy. The prevalence of osteoporosis, osteopenia, and low BMD for age was 42.3%, 44.8%, and 48.6%, respectively. Osteoporosis-related fractures were found in 216 patients (40.8%), whose 34 men under 50 (15.7%). Up to 17.5% of men with fractures had normal BMD. A total of 181 patients (33.8%) had never received calcium/vitamin D supplementation or bone-active therapy; the prevalence of treatment-naïve patients was 20-23% even among men with fractures or receiving corticosteroids/androgen-deprivation therapy. CONCLUSIONS: Male osteoporosis presents with a high rate of fractures in the real-life clinical practice at a tertiary academic center. The high prevalence of comorbidities associated with bone loss suggests that secondary forms of osteoporosis should be carefully investigated, even in presence of normal BMD. The significant proportion of untreated men-including those with known risk factors or fractures-highlights the urgent need to raise awareness and improve the management of male osteoporosis, especially in primary healthcare.
Associations between urinary biomarkers of drinking-water disinfection byproducts and fasting plasma glucose: results from the TREE study.
Zhang N, Deng YL, Miao Y … +9 more , Zhang M, Zeng JY, Liu PH, Zhu JQ, Liu AX, Li YJ, Li XT, Zhou B, Zeng Q
J Endocrinol Invest · 2026 May · PMID 41460454 · Publisher ↗
PURPOSE: Drinking-water disinfection byproducts (DBPs) have been documented to disrupt glucose homeostasis in toxicological studies, but epidemiological evidence remains scarce. We aimed to investigate drinking-water DBP...
PURPOSE: Drinking-water disinfection byproducts (DBPs) have been documented to disrupt glucose homeostasis in toxicological studies, but epidemiological evidence remains scarce. We aimed to investigate drinking-water DBP exposures in association with fasting plasma glucose (FPG). METHODS: We included 1,406 women participating in the Tongji Reproductive and Environmental (TREE) cohort. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), as biomarkers of drinking-water DBPs, along with FPG, were measured. Hyperglycemia was identified as FPG ≥ 5.6 mmol/L. Multivariable linear and logistic regression models were fitted to quantify the associations of DBP exposures with FPG and hyperglycemia risk. RESULTS: Elevated quartiles of urinary DCAA showed an association with increased hyperglycemia risk [odds ratio (OR) = 1.58, 95% confidence interval (CI): 0.97, 2.61 for the fourth vs. first quartile], particularly among younger women (OR = 3.15, 95% CI: 1.47, 7.05). In BMI-stratified analyses, urinary DCAA and TCAA in relation to higher FPG level (DCAA: 1.05%, 95% CI: 0.10%, 2.00%; TCAA: 0.99%, 95% CI: 0.11%, 1.88%) and hyperglycemia risk (DCAA: OR = 1.50, 95% CI: 1.03, 2.17; TCAA: OR = 1.62, 95% CI: 1.14, 2.27) were observed among women with BMI < 24 kg/m2, but not among women with BMI ≥ 24 kg/m2. CONCLUSIONS: Our results provide new evidence that DBP exposures may contribute to hyperglycemia.
Rare forms of congenital adrenal hyperplasia: pathogenesis, clinical, treatment and management.
Cavarzere P, Lupieri V, Battiston R … +2 more , Mancioppi V, Maffeis C
J Endocrinol Invest · 2026 Mar · PMID 41460453 · Publisher ↗
Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by numerous variants in several genes encoding enzymes involved in adrenal steroidogenesis. While 21-hydroxylase deficit is t...
Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by numerous variants in several genes encoding enzymes involved in adrenal steroidogenesis. While 21-hydroxylase deficit is the most common and well-known form of CAH, accounting for 90%-95% of cases, there are six other forms of CAH, due to mutations in the genes of other key enzymes involved in adrenal steroidogenesis. These forms are less frequent and, consequently, clinician experience is extremely limited. These disorders are 11β-hydroxylase deficiency (11βOHD); 17α-hydroxylase/17,20-lyase deficiency (17OHD); 3β-hydroxysteroid dehydrogenase type 2 deficiency (3ΒHSD2D); P450 oxidoreductase deficiency (PORD); steroidogenic acute regulatory protein (StAR) deficiency, causing congenital lipoid adrenal hyperplasia and cholesterol side-chain cleavage enzyme (P450scc) deficiency. This narrative review therefore focuses on these rarer forms of CAH, providing an update on their clinical presentation, diagnosis, management, and treatment.
Safety and glycemic outcomes of DBLG1 coupled to the DANA-i pump in adults and adolescents with type 1 diabetes mellitus. The SP8 trial.
Franc S, Reznik Y, Amadou C … +12 more , Penfornis A, Schaepelynck P, Hanaire H, Delemer B, Le Tallec C, Beltrand J, Jeandidier N, Bensaid S, Orlando L, Hannaert P, Benhamou PY, Charpentier G
J Endocrinol Invest · 2026 Apr · PMID 41452442 · Publisher ↗
PURPOSE: DBLG1 is a hybrid closed-loop (CL) system interoperable with ViCentra Kaleido and Roche Insight pumps. The SP8 trial investigated the safety and glycemic outcomes of DBLG1 coupled to the DANA-i pump (DBLG1-DANAi...
PURPOSE: DBLG1 is a hybrid closed-loop (CL) system interoperable with ViCentra Kaleido and Roche Insight pumps. The SP8 trial investigated the safety and glycemic outcomes of DBLG1 coupled to the DANA-i pump (DBLG1-DANAi) in adults and adolescents with type 1 diabetes mellitus (T1D). METHODS: The safety of DBLG1-DANAi (primary outcome of SP8) was evaluated using two criteria: (i) the incidence of serious adverse device events (SADEs) and (ii) the time spent in hypoglycemia (time below range 70 mg/dL [3.9 mmol/L], TBR70) with DBLG1-DANAi compared to an SAP (sensor-augmented pump) system. Secondary outcomes included non-serious adverse events and standard glycemic metrics. Five months after its start, the trial was halted due to the COVID-19 crisis. One hundred and forty (140) of the 148 planned adults had already been included in the study, as well as all planned adolescents (N = 36). RESULTS: The intention-to-treat (ITT) population included 105 adult and 36 adolescent participants in whom no SADE was observed with DBLG1-DANAi. The per-protocol (PP) population consisted of 73 adults and 18 adolescents who spent two weeks with SAP, followed by two weeks with DBLG1-DANAi. No increase in TBR70 was observed during the DBLG1-DANAi period. Furthermore, the time spent in the glucose level range of 70-180 mg/dL [3.9-10.0 mmol/L] (time in range, TIR70-180) increased significantly with DBLG1-DANAi, both in adults (+ 10.5%; p < 0.0001) and adolescents (+ 16.0%; p < 0.0001). CONCLUSION: During the two-week study period, DBLG1 was interoperable with the DANA-i pump. This result requires confirmation in future long-term studies. GOV ID: NCT04190277.
Metabolic and renal effects of combined SGLT-2 inhibitors and GLP1-R agonists therapy in type 2 diabetes: a real-world analysis across DKD and non-DKD patients.
Mazzeo L, Wolde Sellasie S, Pecchioli C … +9 more , Di Perna P, Zaccaria S, Sperti P, Nardone I, Giurato L, Della-Morte D, Caprio M, Bellia A, Uccioli L
J Endocrinol Invest · 2026 Mar · PMID 41452441 · Publisher ↗
PURPOSE: This study aimed to evaluate the one-year metabolic and renal effects of combined therapy with SGLT-2 inhibitors and GLP-1 receptor (GLP-1R) agonists in patients with type 2 diabetes mellitus (T2DM), both with a...
PURPOSE: This study aimed to evaluate the one-year metabolic and renal effects of combined therapy with SGLT-2 inhibitors and GLP-1 receptor (GLP-1R) agonists in patients with type 2 diabetes mellitus (T2DM), both with and without diabetic kidney disease (DKD). The primary objective was to assess changes in BMI, HbA1c, LDL-C, eGFR, and UACR in a real-world setting. METHODS: A retrospective analysis was conducted on 250 patients with type 2 diabetes mellitus (T2DM) treated with SGLT-2 inhibitors and GLP-1 receptor agonists at the Diabetology Service of CTO-Alesini Hospital, Rome, between 2022 and 2025. Metabolic and renal parameters were collected at baseline and after 12 months. Patients were stratified according to the presence of diabetic kidney disease (DKD). The primary outcomes included changes in BMI, HbA1c, LDL-C, eGFR, and UACR. Secondary analyses evaluated the impact of adding an SGLT-2 inhibitor to pre-existing GLP-1 receptor agonist therapy, or vice versa. RESULTS: After 12 months, we observed significant reductions in BMI (p = 0.03), HbA1c (p < 0.001), LDL-C (p < 0.01), and UACR (p < 0.001). In patients with DKD (46% of the cohort), UACR improved markedly (p < 0.001), while eGFR remained stable. Significant reductions in HbA1c (p < 0.001) and LDL-C (p < 0.01) were also observed. In non-DKD patients, HbA1c and LDL-C decreased after one year, with eGFR remaining within the normal range. Importantly, among DKD patients, the addition of an SGLT-2 inhibitor to GLP-1 receptor agonist therapy resulted in significant reductions in both HbA1c (p = 0.04) and UACR (p < 0.01), whereas the addition of a GLP-1 receptor agonist primarily reduced HbA1c (p < 0.01). In non-DKD patients, both treatment sequences improved HbA1c and LDL-C. CONCLUSION: Dual therapy with SGLT-2 inhibitors and GLP-1 receptor agonists was associated with improvements in glycemic control, lipid profile, and albuminuria, particularly among patients with DKD. The sequence of drug addition appeared to influence outcomes, with the addition of SGLT-2 inhibitors providing superior renal benefits in DKD. These findings may provide support for early combined use of both agents in high-risk patients with T2DM.
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