J. Endocrinol. Invest. [JOURNAL]
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200 papers
Adrenalectomy improves cardiovascular profile in patients with mild autonomous cortisol secretion: extension of a multicenter randomized controlled trial to 12 months.
Morelli V, Strata M, Palmieri S … +10 more , Aresta C, Favero V, Frigerio S, Pugliese F, Musolino A, Dall'Antonia A, Corbetta S, Arosio M, Scillitani A, Chiodini I
J Endocrinol Invest · 2026 Apr · PMID 41940913 · Publisher ↗
PURPOSE: The best therapeutic approach in patients with mild autonomous cortisol secretion (MACS) is debated. In this extension of a randomized controlled trial to 12 months we aimed to evaluate the effect of adrenalecto...
PURPOSE: The best therapeutic approach in patients with mild autonomous cortisol secretion (MACS) is debated. In this extension of a randomized controlled trial to 12 months we aimed to evaluate the effect of adrenalectomy on blood pressure, cardiac structure and coagulation factors in outpatients with MACS. METHODS: patients with unilateral adrenal incidentaloma ≥ 1 cm and cortisol after 1 mg dexamethasone suppression test (F-1mgDST) between 1.8 (50 nmol/L) and 5 µg/dL (138 nmol/L) were enrolled and randomized to adrenalectomy (Arm-A) or conservative approach (Arm-B). Blood pressure control, echocardiographic indices and coagulation factors, were assessed at baseline and 12 months after recovery or observation, in Arm-A and Arm-B, respectively. RESULTS: 51 subjects (23/28 in Arm-A/Arm-B) were enrolled. At follow-up the prevalence of blood pressure improvement was higher in Arm-A (10/23 patients, 43.5%) than in Arm-B patients (4/28 patients, 14.3%, p = 0.02). The improvement of blood pressure control was 5.4-fold more frequent in Arm-A patients (CI, 1.16–24.9 p = 0.03), regardless of confounding factors. In Arm-A, left ventricular mass, left atrial area and the prevalence of left atrial dilatation decreased at follow-up (96.4 ± 28.8 vs 87.6 ± 25,6 g/m2, p = 0.02; 28.4 ± 9.9 vs 22.6 ± 12.4 cm2, p = 0.04, 70.6% vs 35.3% p = 0.04, respectively) whereas all these parameters remained stable in Arm-B. At the end of follow-up, Arm-A patients had a lower prevalence of altered anti-coagulant parameters than Arm-B patients (2/19 patients, 10.5% vs 13/24 patients 54.2%, respectively, p = 0.002). CONCLUSION: In patients with MACS, surgery ameliorates blood pressure, cardiac structure, and coagulation factors. TRIAL REGISTRATION: NCT number 04860180.
Nutritional knowledge in patients with severe obesity during a residential rehabilitation: the relationships with socio-demographic variables.
Mambrini SP, Vinci C, Soranna D … +7 more , Sola D, Barbieri V, Bussi I, Rendina R, Zambon A, Bertoli S, Scacchi M
J Endocrinol Invest · 2026 May · PMID 41925758 · Full text
BACKGROUND: This study was aimed at evaluating the enhancement of nutritional knowledge in severely obese patients participating in a residential rehabilitation program, by means of the Moynihan Questionnaire (M.Q.). It...
BACKGROUND: This study was aimed at evaluating the enhancement of nutritional knowledge in severely obese patients participating in a residential rehabilitation program, by means of the Moynihan Questionnaire (M.Q.). It further explored the association between learning outcomes and socio-demographic variables. METHOD: A cohort of 2888 obese patients (mean Body Mass Index, BMI: 44 ± 7 kg/m^2, mean age 59 yrs.), admitted to Auxologico Piancavallo for metabolic rehabilitation was investigated. Patients underwent an educational course on nutrition and completed the M.Q. upon both admission and discharge. A subgroup of 230 patients, admitted twice, provided additional insights into the sustained impact of the intervention. The analysis utilized a linear regression model (ANCOVA) to identify determinants of score changes during the initial hospitalization and an ANOVA for repeated measurements to assess differences in score changes between the first and second hospitalizations. Multivariate techniques were employed to examine the influence of potential variables on nutritional knowledge outcomes. RESULTS: The rehabilitation program led to a significant improvement in M.Q. at discharge, corroborating the effectiveness of the educational intervention in enhancing nutritional knowledge. While a similar improvement was observed during second admissions, the magnitude of this improvement was notably less than that recorded during initial admissions. Interestingly, score improvements were more pronounced in women, younger patients, those with higher educational levels, married individuals, and participants with higher initial scores. No significant correlation was found between BMI and learning outcomes. CONCLUSION: The M.Q. documented improvements in nutritional knowledge among severely obese patients undergoing educational interventions in a residential setting. Our findings emphasize the influence of socio-demographic variables on the efficacy of nutritional education, highlighting the need for tailored approaches in dietary rehabilitation programs to optimize patient outcomes.
Patient characteristics and prognostic factors in advanced treatment lines in metastatic neuroendocrine tumors.
Melhorn P, Zhitia G, Raderer M … +1 more , Kiesewetter B
J Endocrinol Invest · 2026 Mar · PMID 41915358 · Publisher ↗
BACKGROUND: Given the biological heterogeneity of neuroendocrine tumors (NET), several prognostic factors such as morphology, primary site, and certain blood markers have been identified. However, their prognostic signif...
BACKGROUND: Given the biological heterogeneity of neuroendocrine tumors (NET), several prognostic factors such as morphology, primary site, and certain blood markers have been identified. However, their prognostic significance in the context of advancing treatment lines and late-stage disease is unclear. METHODS: In this retrospective monocentric study, patient characteristics including blood-based inflammation indices at initiation of different lines of therapy (LoT) were assessed, and potential prognostic factors were evaluated with regard to overall survival (OS) from LoT start. RESULTS: A total of 254 patients with NET G1/G2 (74%), NET G3 (8%), or typical/atypical carcinoid (18%) were included. All tumors were metastatic at treatment start, originating from the small intestine (36%), pancreas (28%), lung (17%), or other sites (19%). All patients had at least one palliative systemic therapy, the most frequent initial LoT was somatostatin analogs (SSA, n = 160, 63%), the most common second/third line peptide receptor radionuclide therapy (PRRT, n = 79 or 48% and n = 20 or 27%, respectively). Median OS from first-line start was 84.3 months (n = 250), and 48.6 months (n = 162) and 37.2 months (n = 75) from second- and third-line start, respectively. Patients reaching later LoT were more likely to have pancreatic NET with higher (≥ 10%) Ki-67 values. In univariate analysis, elevation of alkaline phosphatase (ALP) and chromogranin A (CGA) were negative prognostic factors in the first and second LoT subpopulation. Blood-based inflammation indices showed mixed prognostic value. CONCLUSION: Patients at the start of an early versus later LoT had different clinical characteristics, treatment patterns, and prognosis. These insights might help to refine prognosis estimates.
Gouty tophi in Domenico Fetti's Archimedes: a clinico-iconographic analysis.
Bobu AM, Cucu AI, Bianucci R
J Endocrinol Invest · 2026 Mar · PMID 41903030 · Publisher ↗
PURPOSE: To propose a clinico-iconographic diagnosis of gouty tophi in Domenico Fetti’s painting Portrait of a Scholar (Archimedes) and to evaluate the morphological features in relation to differentialdiagnoses such as...
PURPOSE: To propose a clinico-iconographic diagnosis of gouty tophi in Domenico Fetti’s painting Portrait of a Scholar (Archimedes) and to evaluate the morphological features in relation to differentialdiagnoses such as osteoarthritis and rheumatoid arthritis. METHODS: A detailed visual and morphological analysis of the painting was conducted, focusing on the anatomical features of the depicted hand. The observed characteristics were interpreted within aclinical framework and compared with known manifestations of gout, osteoarthritis, and rheumatoid arthritis. The evaluation followed the International Guidelines for Iconodiagnosis. RESULTS: The painting shows nodular formations at the level of the thumb, as well as the proximal and distal interphalangeal joints of the index finger and the interphalangeal joint of the third finger.These features are consistent with tophaceous deposits observed in chronic gout. The distribution and morphology of the nodules are less compatible with osteoarthritis and rheumatoid arthritis, basedon their typical clinical patterns. CONCLUSIONS: The clinico-iconographic correlation supports a retrospective diagnosis of probable chronic gouty arthritis, with a Level of Evidence II. This study highlights the value of artworks as potentialhistorical sources for medical observation, bridging art history and clinical interpretation.
Impact of metabolic comorbidities on the clinical course of West Nile virus infection.
Guarisco G, Milani I, Leonetti F … +7 more , Capoccia D, Chinucci M, Mancarella G, Marocco R, Lichtner M, Borgo CD, Parente A
J Endocrinol Invest · 2026 Mar · PMID 41886254 · Publisher ↗
BACKGROUND: Italy has experienced a marked increase in the incidence of human infections caused by West Nile virus (WNV). Metabolic and other comorbidities, particularly hyperglycemia, are associated with unfavorable out...
BACKGROUND: Italy has experienced a marked increase in the incidence of human infections caused by West Nile virus (WNV). Metabolic and other comorbidities, particularly hyperglycemia, are associated with unfavorable outcomes in infectious diseases. This study aimed to investigate the association between metabolic comorbidities, with a specific focus on blood glucose (BG) levels at hospital admission, and the clinical course of WNV infection. METHODS: 34 patients (22 males, 12 females, mean age 69 ± 14 years) with confirmed WNV infection were included. Clinical history, metabolic comorbidities, anthropometric and biochemical parameters at admission, and outcomes were collected. RESULTS: Arterial hypertension (35.3%), dyslipidemia (23.5%), and diabetes mellitus (8.8%) were highly represented metabolic comorbidities. 35.3% of patients had two comorbidities and 32.4% had three comorbidities, all of which included at least one of the metabolic comorbidities, while more than half had fasting BG levels ≥ 100 mg/dL or fasting BG levels > 125 mg/dL at admission. Duration of hospital stay increased significantly with BG category, with more days observed in patients with BG ≥ 100 mg/dL, whereas no significant differences were observed between Body Mass Index (BMI) groups. Correlation analyses showed a positive association of BG levels with days of hospitalization and Cerebrospinal fluid (CSF) glucose concentration. Patients who died had at least two comorbidities and BG levels > 125 mg/dL at admission. CONCLUSION: These results highlight the importance of BG levels at admission as a prognostic factor in WNV infection. Early recognition and management of elevated BG levels may be an important adjunct in the clinical care of affected patients.
Serum mTOR: an associative marker of Graves' orbitopathy.
Lanzolla G, Dottore GR, Comi S … +9 more , Cosentino G, Maglionico MN, Posarelli C, Ciampa DA, Chiapparelli G, Menconi F, Figus M, Santini F, Marinò M
J Endocrinol Invest · 2026 Mar · PMID 41879896 · Publisher ↗
OBJECTIVE: mTOR is involved in the pathogenesis of Graves’ orbitopathy (GO). Because mTOR can be detected in the bloodstream, we postulated that serum mTOR could be associated with GO. Thus, we evaluated serum mTOR in GO...
OBJECTIVE: mTOR is involved in the pathogenesis of Graves’ orbitopathy (GO). Because mTOR can be detected in the bloodstream, we postulated that serum mTOR could be associated with GO. Thus, we evaluated serum mTOR in GO. METHODS: mTOR was measured by ELISA in serum samples from 77 consecutive patients with Graves’ hyperthyroidism (GH), 57 of whom with GO and in 19 healthy subjects. The primary endpoint was serum mTOR in GH patients with GO vs GH patients without GO. RESULTS: Median serum mTOR was 2440 pg/ml (1236–3053) in GO patients, 1236 pg/ml (388.5–1770) in GH without GO, and 247 pg/ml (0.9–705) in healthy subjects. mTOR was greater in GH than in healthy subjects (P=0.00012), and, within GH, in patients with GO (P = 0.0023). In GO patients, there was a direct correlation between mTOR and the clinical activity score (R = 0.377; P = 0.0038) and mTOR was higher in moderate-to-severe than in mild GO (P = 0.016). We established a cut-off value of 1445.8 pg/ml of serum mTOR (97th percentile in healthy subjects) that distinguished GO patients within GH [positive predictive value (PPV): 79.2%; sensitivity: 73.6%; specificity: 55%]. CONCLUSIONS: Serum mTOR is associated with GH, in particular with the presence, activity and severity of GO. Additional studies are required to determine whether serum mTOR can be used as a biomarker in clinical practice.
Successful sexual aging: A narrative review using the multidimensional theoretical paradigm of systems sexology to explore sexual health in midlife and older adults.
Tang D, Zhang Y, Wu X … +2 more , Zhang X, Jannini EA
J Endocrinol Invest · 2026 Mar · PMID 41879895 · Publisher ↗
PURPOSE: Global population aging is shifting healthcare priorities from merely extending life to enhancing quality of life, yet sexuality remains a neglected dimension of healthy aging. Prevailing approaches focus on dis...
PURPOSE: Global population aging is shifting healthcare priorities from merely extending life to enhancing quality of life, yet sexuality remains a neglected dimension of healthy aging. Prevailing approaches focus on discrete sexual dysfunctions such as erectile dysfunction, menopause-related dyspareunia, or late-onset hypogonadism, overlooking the multidimensional and dyadic nature of sexual aging. This review reframes successful sexual aging (SSA) as a biopsychosocial process evaluated in the light of the new systems sexology, integrating decline and adaptation, and introducing the paradigm of SSA grounded in acceptance, adaptation, and activation. METHODS: We conducted a narrative review of literature across sexual medicine, geriatrics, endocrinology, urology, gynecology, psychiatric, psychology, sociology, and regenerative medicine. We critically examined central theoretical constructs of CouplePause and DoublePause along with validated assessment instruments and a proposed conceptual framework, the Sexual Aging Index (SAI), intended to guide future multidimensional assessment of sexual aging. Evidence synthesized from gender-specific and cross-cultural perspectives illuminated key conceptual voids, translational barriers, and novel opportunities to advance the field of sexual aging research. RESULTS: Sexual aging is shaped by endocrine decline, neurovascular changes, psychological resilience, sociocultural norms, and relational dynamics. Men commonly experience gradual androgen and vascular decline, while women face abrupt transitions linked to menopause and genitourinary syndrome of menopause (GSM), yet both trajectories are strongly moderated by adaptation and couple dynamics. Current assessment instruments fail to adequately capture aging-specific, dyadic dimensions, highlighting the need for multidimensional tools like the SAI. Interventions extend beyond pharmacology to include translational Chinese medicine (TCM), functional nutrition, low intensity extracorporeal shock wave therapy (Li-ESWT), platelet-rich plasm (PRP), stem cell therapies, and vaginal energy-based devices, though evidence remains heterogeneous. The SSA framework reframes it as a positive, process-oriented phenomenon linked to quality of life and relational health, while challenging sexual ageism at individual, clinical, and policy levels. CONCLUSIONS: Sexual aging represents an emerging frontier in sexual medicine, demanding a shift from deficit-based models to an integrative, couple-centered, and culturally inclusive paradigm. Advancing this field will require international consensus on definitions and frameworks, the development of validated multidimensional assessment tools, the implementation of rigorous multimodal clinical trials, and societal initiatives to dismantle sexual ageism. Embedding sexual health into healthy aging policies, healthcare delivery, and medical education will be critical to ensure that intimacy, dignity, and sexual vitality remain integral to longevity in the twenty-first century.
The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes.
Idoate-Bayón A, Ainzúa E, Marqués J
J Endocrinol Invest · 2026 Mar · PMID 41879894 · Publisher ↗
BACKGROUND: The Langerhans islets are highly vascularized structures that regulate plasma glucose levels. These islets are primarily composed of different types of endocrine cells (α, β, δ, PP, and ε) and endothelial cel...
BACKGROUND: The Langerhans islets are highly vascularized structures that regulate plasma glucose levels. These islets are primarily composed of different types of endocrine cells (α, β, δ, PP, and ε) and endothelial cells. The paracrine signalling between pancreatic β-cells and endothelial cells is key for maintaining β-cell mass and preserving endocrine function. Oxidative stress, caused by an excess of reactive oxygen species (ROS), is a pathological mechanism that damages pancreatic β-cells and endothelial cells. AIM: In this review, we discuss how oxidative stress impacts not only on endothelial and pancreatic β-cells individually, but also on their paracrine signalling. RESULTS: Oxidative stress triggers apoptosis and dysfunction of endothelial and pancreatic β-cells, as well as it alters glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Moreover, oxidative stress affects to the homeostasis of vascular endothelial growth factor (VEGF) and Heparin-binding Epidermal Growth Factor (HB-EGF), two key mediators of the β-cell-endothelial cell crosstalk. Finally, an oxidative environment in the Langerhans islets promotes inflammation by increasing the secretion of cytokines, which impact in both cell types, further impairing insulin production. CONCLUSION: These effects of oxidative stress on the endothelial cell-β-cell paracrine signalling may represent a promising therapeutic target to alleviate diabetes development and its derived complications.
Mutational patterns in a large cohort of parathyroid carcinomas.
Pandya C, Uzilov AV, Costa-Guda J … +19 more , Bellizzi J, Taik P, Moe AS, Strahl M, van der Tuin K, Stevenson M, Cavaco BM, Cetani F, Marcocci C, Karhu A, Arola J, Schalin-Jäntti C, Morreau H, Thakker RV, Schadt EE, Sebra R, Li SD, Chen R, Arnold A
J Endocrinol Invest · 2026 Mar · PMID 41879893 · Publisher ↗
PURPOSE: A lack of targeted therapies make parathyroid carcinoma, a diagnostically challenging malignancy, difficult to treat. The rarity of this tumor type necessitates international collaboration to collect a sizable s...
PURPOSE: A lack of targeted therapies make parathyroid carcinoma, a diagnostically challenging malignancy, difficult to treat. The rarity of this tumor type necessitates international collaboration to collect a sizable sample set for study. Prior studies have revealed the importance of driver mutations in the CDC73 gene and identified several putative drivers/aberrant pathways including PI3K/mTOR activation and CCND1 (cyclin D1) amplification. In this study, we sought to better understand the prevalence of putative oncogenic drivers in parathyroid carcinoma. METHODS: We subjected an expanded cohort of 71 sporadic parathyroid carcinomas, fulfilling stringent WHO criteria, to next-generation DNA sequencing on a custom 16-gene targeted panel. RESULTS: One or more variant was detected in 44 tumors (62%) and 27 (38%) had no detectable variant. Consistent with earlier studies, we detected loss-of-function CDC73 mutations in 44% (31/70) of evaluable patients, including germline pathogenic variants in 9 patients (36 patients evaluable for somatic status as matched normal available). Notably, mutations in the PI3K/AKT/mTOR pathway were seen in 12.9% (9/70) of evaluable patients, providing further evidence of this as a key therapeutically actionable pathway in parathyroid carcinoma. Correlating genomic and clinical features revealed that patients harboring CDC73 mutations are more likely suffer from life threatening recurrent/metastatic parathyroid carcinoma (P = 0.024) than those without CDC73 variants. CONCLUSIONS: This genomic characterization of a large parathyroid carcinoma cohort improves understanding of the genomic underpinnings of this rare malignancy, provides novel evidence for genotype-phenotype correlation with recurrent/metastatic disease, and may help to provide a rational basis for individualized treatments.
Chronic cholecalciferol supplementation and adequate vitamin D status are associated with reduced risk of Long COVID.
di Filippo L, Terenzi U, Bolamperti S … +6 more , Bechini C, Bossoni S, Campaniolo M, Gifuni L, Doga M, Giustina A
J Endocrinol Invest · 2026 Mar · PMID 41870866 · Publisher ↗
INTRODUCTION: Vitamin D deficiency has been associated with adverse acute and long-term COVID-19 outcomes. However, data on its supplementation on post-acute recovery are still limited. This retrospective observational s...
INTRODUCTION: Vitamin D deficiency has been associated with adverse acute and long-term COVID-19 outcomes. However, data on its supplementation on post-acute recovery are still limited. This retrospective observational study investigated the role of chronic cholecalciferol supplementation and 25(OH) vitamin D concentrations on Long COVID risk. METHODS: We included patients with COVID-19 between March 2020 and May 2021 previously followed at our Endocrine Department. Long COVID was defined according to NICE criteria. Patients chronically supplemented with cholecalciferol were compared with matched controls for age, sex, comorbidities, and COVID-19 severity. RESULTS: A total of 132 patients were evaluated; 50 (38%) received cholecalciferol supplementation and 30 (22.7%) developed Long COVID. Long COVID occurred less frequently among supplemented patients (14% vs. 28%, p = 0.086), particularly with daily-doses ≥ 750 IU (12.5% vs. 28.6%, p = 0.051) and ≥ 1000 IU (10.5% vs. 27.6%, p = 0.039). Baseline 25(OH)D concentrations were significantly lower in those with Long COVID (p = 0.02), and showed a significant predictive performance for Long COVID (AUROC 67.3%, p = 0.023). In the matched cohort (n = 86), Long COVID occurred less frequently among supplemented patients (11.6% vs. 32.6%, p = 0.036) and similar findings were confirmed in the matched subgroup receiving ≥ 1000 IU/day (8.5% vs. 34.2%, p = 0.018). Multivariate analyses showed a protective role of cholecalciferol supplementation on Long COVID in both entire and matched cohorts. CONCLUSIONS: Chronic cholecalciferol supplementation, particularly at daily doses ≥ 750–1000 IU, was associated with a significantly lower risk of Long COVID. Ensuring adequate vitamin D status may represent a potential useful preventive strategy for post-COVID sequelae.
Synergic effect of diet and polysaccharide-based complex administration in the treatment of children and adolescents with metabolically unhealthy obesity: the Polymets Study.
Fiore G, Altayeva A, Panelli S … +8 more , De Zan D, Sterzi L, Calcaterra V, Tosi M, Folli F, Zuccotti G, Comandatore F, Verduci E
J Endocrinol Invest · 2026 Mar · PMID 41831138 · Publisher ↗
PURPOSE: The primary aim of the Polymets Study is to evaluate the effect on gut microbiota composition of a polysaccharide-based complex administration combined with dietary and lifestyle interventions in a group of chil...
PURPOSE: The primary aim of the Polymets Study is to evaluate the effect on gut microbiota composition of a polysaccharide-based complex administration combined with dietary and lifestyle interventions in a group of children and adolescents with metabolically unhealthy obesity (MUO). METHODS: In this clinical trial, children and adolescents (8–14 years) with obesity (defined as body mass index > + 2 standard deviation score [BMI SDS] according to World Health Organization) and cardio-metabolic alteration (hypertriglyceridemia, hypertension, hypo-HDL cholesterol, altered glucose metabolism) were enrolled. Participants received from baseline (T0) to 4 months (T1) combined polysaccharide-based complex administration (5 g/day mixture of soluble and insoluble fibres) and Mediterranean diet intervention; from 4 to 8 months (T2) they underwent dietary intervention alone. At T0, T1 and T2 gut microbiota analysis, body composition assessment, blood tests and Mediterranean diet adherence (KIDMED score) were assessed. RESULTS: Overall, 31 children were enrolled (10.9 ± 1.6 years, F/M 8/23). BMI SDS significantly decreased at each timepoint (p < 0.001), whilst fat mass% significantly decreased only at T1 (p = 0.035), vs T0. The Principal Component Analysis showed a trend of reduced dispersion at the phylum taxonomic level at T1, having Firmicutes, Bacteroidota and Proteobacteria as major contributors to the variance. At T1, there was an enrichment in Barnesiellaceae family, Erysipelotrichaceae_UCG-003 and Parabacteroides genera (p < 0.05), vs. T0. At T2 Oscillospiraceae_unclassified and Clostridia_unclassified increased significantly, whereas Erysipelotrichaceae_UCG − 003 and Escherichia_Shigella decreased significantly (p < 0.05), vs T1. CONCLUSION: Polysaccharide-based complex intervention synergistically contributes for enrichment in microbial marker of metabolic health and body adiposity reduction, while the subsequent solo-diet phase triggers expansion of butyrate-producing lineages and overall reduction of pathogenic taxa.
Trabecular bone score enhances fracture risk stratification in patients with metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus.
Asero C, Oliveri C, Franzè MS … +10 more , Di Giovanni A, Filomia R, Caccamo G, Pitrone C, Saitta C, Morace C, Morabito N, Basile G, Catalano A, Cacciola I
J Endocrinol Invest · 2026 Mar · PMID 41817922 · Publisher ↗
PURPOSE: Alterations in bone metabolism are common in chronic liver disease. This study aimed to assess the risk of fragility fractures in patients with metabolic dysfunction–associated steatotic liver disease (MASLD) an...
PURPOSE: Alterations in bone metabolism are common in chronic liver disease. This study aimed to assess the risk of fragility fractures in patients with metabolic dysfunction–associated steatotic liver disease (MASLD) and type 2 diabetes (T2D), using the trabecular bone score (TBS) as a marker of bone quality. METHODS: Patients with MASLD and T2D were consecutively enrolled at the Medicine and Hepatology Unit of the University Hospital of Messina between February and October 2024. Exclusion criteria included decompensated cirrhosis, secondary osteoporosis, and long-term use of bone-active therapies. All participants underwent liver elastography for steatosis and fibrosis assessment, with the Controlled Attenuation Parameter (CAP) used to quantify hepatic fat content, and dual-energy X-ray absorptiometry with TBS and vertebral fracture assessment. RESULTS: One hundred-five patients (56 males; median age 62 years) were included in the study. Vertebral fractures were detected in 54 patients (51.4%), of whom 45 (83.3%) had pathological TBS (< 1.350) despite normal bone mineral density. Regression analysis confirmed a strong association between pathological TBS and fracture risk (p < 0.001). Pathological TBS was also significantly associated with body mass index > 30 kg/m2 (p < 0.001), CAP ≥ 248 dB/m (p = 0.034), and male sex (p = 0.002), but not with advanced liver fibrosis. CONCLUSION: Bone fragility represents a relevant comorbidity in patients with MASLD and T2D, independent of fibrosis severity. TBS appears to be a sensitive marker of skeletal fragility, while CAP may help identify patients at increased risk of fracture.
Clinical characteristics of chinese patients with autosomal dominant hypocalcemia type 1: a single-center study.
Gao Y, Jiang Y, Wang Y … +9 more , Yang J, Wang J, Song A, Jiang Y, Li M, Xia W, Xing X, Nie M, Wang O
J Endocrinol Invest · 2026 Mar · PMID 41801666 · Publisher ↗
OBJECTIVE: Autosomal dominant hypocalcemia type 1 (ADH1) is rarely reported in Chinese populations except for isolated cases. This study aimed to describe the clinical characteristics of a group of Chinese patients with...
OBJECTIVE: Autosomal dominant hypocalcemia type 1 (ADH1) is rarely reported in Chinese populations except for isolated cases. This study aimed to describe the clinical characteristics of a group of Chinese patients with genetically confirmed childhood-onset ADH1 and compare them with patients diagnosed with idiopathic hypoparathyroidism (IHP). METHODS: This retrospective study analyzed 210 childhood-onset hypoparathyroidism (HP) cases using targeted next-generation sequencing and TBX1-MLPA. Patients harboring rare variants in the CASR gene were identified as ADH1 cases. In vitro functional tests of the variants were performed using a dual-luciferase reporter assay. Patients without any variants or with only benign/likely benign variants in known HP-related genes were classified as IHP for comparison. Clinical presentation, biochemical parameters, and complications were compared between the ADH1 and IHP groups. RESULTS: Thirteen ADH1 patients carried 10 different CASR mutations, including six novel variants, all of which showed higher NFAT activity in functional tests. Median age at hypocalcemia onset was 0.05 years, with an average diagnostic delay of 12.90 ± 9.90 years. Four of them were familial cases. Compared to 124 IHP patients, ADH1 patients showed significantly earlier onset (0.05 vs. 12.67 years), higher 24 h urinary calcium excretion (0.13 vs. 0.04 mmol/kg/day) despite similar serum calcium levels, more frequent hypomagnesemia (61.54 vs. 13.73%), and more urolithiasis (38.46 vs. 10.00%). CONCLUSION: This study extends the known CASR mutation spectrum in ADH1 and highlights key clinical features (early onset, family history, hypomagnesemia, hypercalciuria, and urolithiasis) that may indicate ADH1. It is suggested that the genotyping should be clarified as early as possible in clinical practice, which is crucial for accurate diagnosis and the formulation of effective, personalized treatment strategies.
POLK and KCNK17 as novel candidate genes for type 2 diabetes via stress response and ion channel regulation.
Qu Y, Wang Y, Zhang Y … +2 more , Wu H, Yao Y
J Endocrinol Invest · 2026 Jun · PMID 41793632 · Publisher ↗
PURPOSE: Pancreatic beta-cell dysfunction is a central pathological feature of type 2 diabetes (T2D). However the cell type-specific causal genes underlying β-cell dysfunction remain incompletely defined. METHODS: We ana...
PURPOSE: Pancreatic beta-cell dysfunction is a central pathological feature of type 2 diabetes (T2D). However the cell type-specific causal genes underlying β-cell dysfunction remain incompletely defined. METHODS: We analyzed scRNA-seq data from 17 patients with T2D and 17 healthy controls. Four machine learning models (Random Forest, XGBoost, SVM, L2 regularized logistic regression) were applied to identify key pathogenic cell types. Differentially expressed genes(DEGs) in beta cells were identified using Seurat, and cis-eQTLs (GTEx v8) were intergrated with T2D summary statistics(FinnGen R12) through Mendelian randomizaition(MR) to identify pancreatic genes causally linked to T2D. Beta-cell-specific causal genes were defined by the intersection of beta-cell DEGs and MR-identified genes. Robustness was assessed by Steiger filtering, Bayesian colocalization (PPH4 > 0.8), and phenome-wide association studies (PheWAS). As additional support, we examined POLK expression in a high-glucose-treated beta-cell line and KCNK17 expression in an independent RNA-seq dataset of palmitate-exposed human islets. Functional enrichment (GO/KEGG) analysis were performed to explore fuctional mechanisms. RESULTS: Beta-cells were consistently prioritized as the top contributor to T2D pathogenesis. Integration of scRNA-seq and MR identified eight beta-cell-specificc causal genes. Higher expression of POLK, HLA-C, LINC01099, AGA, and LSAMP increased T2D risk, whereas higher KCNK17 expression was protective, with MR and colocalization results remaining robust across sensitivity analyses. In line with the genetic and single-cell findings, POLK expression was increased in high-glucose-treated beta cells, while KCNK17 expression was reduced in palmitate-exposed human islets. In scRNA-seq defined beta-cell subpopulations, KCNK17+ beta-cells were enriched in ion transport and T2D pathways, with POLK+ beta-cells showed activation of stress response and pancreatic dysfunction pathways. CONCLUSIONS: This study identifies KCNK17 and POLK as β -cell-specific genes with potential relevance to T2D pathogenesis and highlights distinct cellular programs associated with ion transport and stress responses. Our findings provide a cell Type-resolved, multi-omics framework for elucidating causal mechanisms underlying β-cell dysfunction in T2D.
Feasibility of a semiautomated, individualized coaching intervention for glycemic management in adults with type 1 diabetes: a pilot randomized controlled trial.
Kim S, Kim M, Park SH … +6 more , Park S, Lee YB, Jin SM, Hur KY, Kim JH, Kim G
J Endocrinol Invest · 2026 Mar · PMID 41793631 · Publisher ↗
BACKGROUND: In the Korean Type 1 Diabetes Home Care Pilot Project, patients with type 1 diabetes (T1D) receive at least two monthly remote educational consultations from a multidisciplinary team. This randomized trial ev...
BACKGROUND: In the Korean Type 1 Diabetes Home Care Pilot Project, patients with type 1 diabetes (T1D) receive at least two monthly remote educational consultations from a multidisciplinary team. This randomized trial evaluated the feasibility and acceptability of individualized, semi-automated coaching messages based on continuous glucose monitoring (CGM) data for glycemic and emotional management in patients with T1D as a potential alternative to current treatments. METHODS: Participants who had already enrolled in the national home care program for T1D were randomized in a 1:2 ratio to the control or intervention groups. The control group continued their current treatment, while the intervention group received weekly CGM-based coaching messages for glycemic management and biweekly emotional support messages based on the Patient Health Questionnaire-9 (PHQ-9) for six weeks. Feasibility was assessed based on the difference in time in range (TIR; 70–180 mg/dL) at week 6, other CGM metrics, and patient-reported outcomes. RESULTS: Eighteen participants were enrolled. At week 6, the median TIR was 72.6% (interquartile range [IQR], 46.8–77.0) in the control group (n = 6) and 79.0% (IQR, 65.0–82.1) in the intervention group (n = 12), with no significant difference (p = 0.33). The intervention group showed a significantly lower median PHQ-9 score (2.5) in week 6 compared to the control group (6.0) (p = 0.03). CONCLUSION: The use of individualized semi-automated coaching messages was feasible and acceptable for glycemic and emotional management in individuals with T1D. Further large-scale studies are needed to confirm these findings and assess their long-term clinical impact. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06525454).
Navigating thyroid hormone signaling in liver fibrosis: mechanisms and clinical implications.
Ye C, Xu K, Lan X … +4 more , Quan S, Li Y, Yang W, Liu S
J Endocrinol Invest · 2026 May · PMID 41774331 · Full text
BACKGROUND: Thyroid hormones have emerged as critical modulators of hepatic fibrogenesis, exerting regulatory effects through both genomic and non-genomic signaling pathways. Their influence spans multiple cellular proce...
BACKGROUND: Thyroid hormones have emerged as critical modulators of hepatic fibrogenesis, exerting regulatory effects through both genomic and non-genomic signaling pathways. Their influence spans multiple cellular processes, including the activation of hepatic stellate cells, metabolic regulation, inflammation, and extracellular matrix remodelling.This review aims to provide a comprehensive overview of the molecular mechanisms by which THs modulate liver fibrosis, and to explore the therapeutic potential of targeting TH-related signaling in clinical practice. METHODS: We conducted an integrative narrative review of preclinical and clinical studies focusing on TH-mediated regulation of six key signaling pathways: TGF-β/Smad, PI3K/AKT/mTOR, Wnt/β-catenin, AMPK, NF-κB, and MAPK/ERK. Emphasis was particularly placed on their roles in HSC biology and fibrotic progression. RESULTS: Although progress has been made in elucidating TH signaling in liver fibrosis, critical gaps remain—especially regarding downstream signal integration, pathway crosstalk, and human translational evidence. Preclinical studies consistently demonstrate that thyroid hormones exert antifibrotic effects by modulating metabolic and inflammatory pathways; however, clinical data supporting these findings remain limited. Evidence suggests that THs may exert antifibrotic effects via modulation of metabolic and inflammatory networks, and early investigations into THR agonists offer encouraging therapeutic prospects. CONCLUSIONS: Targeting thyroid hormone signaling represents a promising frontier in antifibrotic therapy. Clarifying mechanistic interactions and conducting well-designed clinical trials will be essential to translate these insights into effective interventions for patients with chronic liver disease.
Comparison of pre-operative calcitonin, FNAC, and ultrasound risk stratification systems in patients with medullary thyroid carcinoma.
Matrone A, Gambale C, Torregrossa L … +8 more , Prete A, Rago T, Bottici V, Cappagli V, Rossi L, Ugolini C, Materazzi G, Elisei R
J Endocrinol Invest · 2026 Mar · PMID 41774330 · Publisher ↗
CONTEXT: Although the diagnostic performance of calcitonin (CTN) in revealing medullary thyroid carcinoma (MTC) has been widely demonstrated, to date, neck ultrasound (neck US) and FNAC remain the first-line tools in sea...
CONTEXT: Although the diagnostic performance of calcitonin (CTN) in revealing medullary thyroid carcinoma (MTC) has been widely demonstrated, to date, neck ultrasound (neck US) and FNAC remain the first-line tools in searching for malignancy in thyroid nodules. OBJECTIVE: This study aims to determine which tool is more effective at suggesting MTC among preoperative CTN values and FNAC, compared with the estimated risk of malignancy at neck US according to the 5 main risk stratification systems (RSS), in a population of patients with already diagnosed MTC. METHODS: We evaluated preoperative serum CTN, FNAC, and neck US data in 104 patients with sporadic MTC (2014-2020) managed at the Unit of Endocrinology of the Pisa University Hospital, Italy. RESULTS: According to the neck US RSS, 59.6% of patients were classified as the intermediate-low suspicion (ILS) and 40.4% as the high suspicion (HS) group. FNAC, performed according to clinical judgment in 85/104 (81.7%) cases, was diagnostic of MTC in only 45.9% of cases. Moreover, according to the guidelines, 39 (62.9%) nodules in the ILS and 14 (33.3%) in the HS group would not even be submitted for FNAC. Of note, most of these MTCs had tumor dimensions > 1 cm and/or lymph node metastases. Conversely, the preoperative CTN values suggested at least a suspicion of MTC in both US risk groups and across all MTC US dimension categories, including microcarcinomas. CONCLUSIONS: Among patients with a confirmed diagnosis of MTC, serum CTN values were the most reliable parameter, outperforming ultrasound features and FNAC in diagnostic accuracy. Delaying or failing to diagnose MTC is undesirable if the aim is to achieve early diagnosis and effective treatment of these patients.
Different clinical autoimmune polyglandular syndrome phenotypes among patients with thyroid diseases.
Gatta E, Pirola I, Virili C … +4 more , Croce L, Centanni M, Rotondi M, Cappelli C
J Endocrinol Invest · 2026 Mar · PMID 41770450 · Publisher ↗
PURPOSE: To characterize and compare autoimmune comorbidity patterns and temporal dynamics in patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) within an autoimmune polyglandular syndrome (APS) framewor...
PURPOSE: To characterize and compare autoimmune comorbidity patterns and temporal dynamics in patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) within an autoimmune polyglandular syndrome (APS) framework. METHODS: We retrospectively analysed patients with an autoimmune thyroid disease (AITD) and at least one additional autoimmune disease fulfilling APS criteria, followed at a tertiary APS referral centre between 2000 and 2025. The prevalence of associated autoimmune diseases was compared between HT and GD. Time to development of subsequent autoimmune diseases was assessed using Kaplan–Meier analysis and Cox proportional hazards models, with adjustment for sex and age. RESULTS: A total of 1,057 patients (76% women; mean age 53.7 ± 16.4 years) were included, of whom 964 had HT and 93 GD. Type 1 diabetes was the most frequent autoimmune comorbidity, but was significantly less prevalent in GD than in HT (OR 0.48, 95% CI 0.31–0.75; FDR-adjusted p = 0.008). GD was selectively enriched for systemic sclerosis (OR 51.54, 95% CI 10.96–242.41; FDR-adjusted p < 0.001) and vitiligo (OR 3.46, 95% CI 1.82–6.55; FDR-adjusted p < 0.001). In patients in whom AITD was the first autoimmune manifestation (n = 333), GD was associated with a longer latency to additional autoimmune diseases and a lower hazard of subsequent autoimmunity compared with HT (HR 0.52, 95% CI 0.37–0.73; p < 0.001). CONCLUSION: Within APS-related AITD, HT and GD anchor distinct autoimmune phenotypes with different clustering patterns and temporal trajectories. These differences have relevant clinical implications for risk stratification and personalized surveillance of patients with autoimmune thyroid disease.
Biglycan knockdown improves Graves' orbitopathy (GO)-like features via inhibiting NF-kB and ERK signaling.
Chenzhao C, Zhu M, Zhang F … +4 more , Xie B, Cao J, Xiong W, Tan Y
J Endocrinol Invest · 2026 Mar · PMID 41770449 · Publisher ↗
PURPOSE: Graves' orbitopathy (GO) is an autoimmune disease characterized by orbital inflammation, fibroblast activation, and adipogenesis, with limited effective therapies. This study aimed to investigate the role of big...
PURPOSE: Graves' orbitopathy (GO) is an autoimmune disease characterized by orbital inflammation, fibroblast activation, and adipogenesis, with limited effective therapies. This study aimed to investigate the role of biglycan (BGN) in GO pathogenesis and its underlying mechanisms. METHODS: Bioinformatic analyses were performed to identify differentially expressed genes in GO tissues. BGN protein levels were validated in orbital adipose tissues from GO patients. Functional effects of BGN were examined by overexpression or knockdown in human GO orbital fibroblasts (GO-OFs) in vitro. In vivo, a thyroid-associated ophthalmopathy (TAO) mouse model was used to evaluate the effects of Bgn knockdown on orbital fibrosis and adipogenesis. RESULTS: BGN expression was significantly upregulated in GO orbital tissues. In vitro, BGN overexpression promoted, while BGN knockdown attenuated, fibrosis and adipogenesis in GO-OFs. Mechanistically, BGN activated nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways. In vivo, Bgn knockdown reduced GO-like pathological features, including fibrosis and adipose expansion, and decreased NF‑κB and ERK signaling activation. CONCLUSION: BGN contributes to fibrosis and adipogenesis in GO via NF‑κB and ERK signaling activation. These findings elucidate a pivotal role for BGN in GO pathogenesis and highlight its potential as a therapeutic target for GO treatment.
Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.
Bruno I, De Sanctis L, Foligno NE … +4 more , Giambò F, Mora S, Parolin M, Vezzoli G
J Endocrinol Invest · 2026 Mar · PMID 41770448 · Publisher ↗
PURPOSE: Ectonucleotide pyrophosphate/phosphodiesterase family member 1 (ENPP1) deficiency is a rare genetic disorder caused by loss-of-function ENPP1 gene mutations. Characterized by abnormally low circulating inorganic...
PURPOSE: Ectonucleotide pyrophosphate/phosphodiesterase family member 1 (ENPP1) deficiency is a rare genetic disorder caused by loss-of-function ENPP1 gene mutations. Characterized by abnormally low circulating inorganic pyrophosphate concentrations, bone hypomineralization, soft tissue calcification, and arterial stenosis, ENPP1 deficiency is associated with a phenotypic spectrum that includes generalized arterial calcification of infancy type 1 (GACI1) and autosomal recessive hypophosphatemic rickets type 2 (ARHR2). Despite phenotypic differences, patients with GACI1 and ARHR2 have a marked, lifelong physical and emotional burden, with a negative impact on quality of life. METHODS: A scientific board, comprising seven specialist physicians (endocrinologists, nephrologists, and pediatricians) practicing in Italy, held two virtual meetings to exchange knowledge regarding real-world clinical experience of GACI1 and ARHR2 using case examples, and to discuss strategies on how to increase disease awareness and optimize the diagnosis and management of these patients. RESULTS: Five real-world clinical cases are described. The specialist physicians also provide guidance for optimizing the management pathway for patients with ENPP1 deficiency. Early identification of the clinical signs of disease, in combination with comprehensive diagnostic and follow-up testing, is essential for effective patient management. CONCLUSION: Early and accurate identification of ENPP1 deficiency by healthcare providers and comprehensive diagnostic testing is essential for the effective management of patients with GACI1 and ARHR2. Consistent follow-up is key to preventing complications and adverse outcomes. Although treatment options are limited, novel therapies are currently under clinical development.
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