J. Endocrinol. Invest. [JOURNAL]
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200 papers
Utility of a 40-minute LH level after depot leuprolide for diagnosis and treatment monitoring in girls with CPP.
Helvacioglu D, Turkmen N, Turan S … +5 more , Guran T, Haliloglu B, Tosun BG, Kahveci A, Bereket A
J Endocrinol Invest · 2026 May · PMID 42189483 · Publisher ↗
PURPOSE: Gonadotropin-releasing-hormone (GnRH) stimulation test is used for assessment of gonadotropic activation in patients with central precocious puberty (CPP). However, it is invasive and GnRH preparation is not ava...
PURPOSE: Gonadotropin-releasing-hormone (GnRH) stimulation test is used for assessment of gonadotropic activation in patients with central precocious puberty (CPP). However, it is invasive and GnRH preparation is not available in all countries. Depot-leuprolide acetate (dLA), used for the treatment of CPP, stimulates gonadotropins briefly before suppressing them. This study aimed to evaluate the utility of luteinizing hormone (LH) level measured 40-minutes after dLA injection for assessing gonadotropic activation compared to GnRH stimulation test. METHODS: In this prospective study, girls with idiopathic CPP were randomized to receive dLA 3.75 mg/4 weeks IM, 11.25 mg/12 weeks SC or 11.25 mg/12 weeks IM. A standard GnRH test was performed before (baseline) and after 6 months of treatment. Forty minutes after the first dLA injection, LH and follicle-stimulating hormone (FSH) levels were measured, and the same measurements were repeated after 6 months of treatment. RESULTS: The study recruited 132 girls. Peak LH on the GnRH test did not differ from the 40-minute-post-dLA LH levels [11.0(6.8-17.1) vs. 9.4(5.8-16.6); p = 0.06]. There were no significant differences between the treatment groups. Using the GnRH test peak of LH ≥ 5 IU/L as the gold-standard, ROC analysis identified the optimal cut-off of post-dLA injection LH ≥ 5.4 IU/L on initial measurement (sensitivity = 86%, specificity = 90% and AUC = 0.91). At 6 months, peak LH levels in treatment groups were similarly suppressed (2.1 ± 1.6, 2.5 ± 1.8, 2.2 ± 0.9; p = 0.2011). Furthermore, post- dLA LH cut-off of < 3.07 IU/L yielded an AUC = 0.83, sensitivity = 80.8% and specificity = 75.5%. CONCLUSION: The 40-minute post-dLA LH provided clinically useful information concerning gonadotropic activity for both diagnosis and treatment monitoring and may provide a practical and clinically informative alternative in selected settings, particularly when standard GnRH testing is not readily available.
Building the adult growth hormone deficiency data mart: a Real-World model of AI-driven clinical data extraction in a single Italian center.
Vergani E, Iacomini C, Giampietro A … +7 more , Milardi D, Chiloiro S, Mancini A, De Marinis L, Bianchi A, Patarnello S, Pontecorvi A
J Endocrinol Invest · 2026 May · PMID 42189482 · Publisher ↗
PURPOSE: Adult Growth Hormone Deficiency (AGHD) is a complex and under-recognized condition, mainly managed in outpatient settings and characterized by fragmented and heterogeneous clinical data. Population registries pr...
PURPOSE: Adult Growth Hormone Deficiency (AGHD) is a complex and under-recognized condition, mainly managed in outpatient settings and characterized by fragmented and heterogeneous clinical data. Population registries provide high-quality evidence but require long timeframes and substantial resources. The aim of this study was to design and validate an artificial intelligence (AI)-driven methodology for the construction of a disease-specific AGHD Data Mart from routine clinical data within a single high-volume center, to support real-world evidence generation and future advanced analytics. METHODS: A standardized Data Science framework, based on automated extraction from hospital data warehouses and electronic medical records, integrating structured data and unstructured clinical narratives through natural language processing, was implemented. AGHD patients were identified using a combination of ICD-9 codes and text-mining applied to outpatient reports. A multidisciplinary workflow ensured clinical validation of extracted data. The Data Mart described patient identification from first hospital access (T0) and included diagnostic modality, etiology, biochemical data, comorbidities, and growth hormone replacement therapy. RESULTS: Among 210 identified patients, 188 were validated as AGHD after expert review. Diagnoses were based on dynamic testing (28.2%), panhypopituitarism with low IGF-1 (54.3%), or AI-assisted identification (17.6%). Etiology was retrieved in 87.8% of cases, with post-surgical causes being the most frequent. 37.8% of patients were receiving rhGH therapy. Specific trends for IGF-1 values for single patients were described. CONCLUSION: This study represents the first AI-driven AGHD Data Mart and demonstrates the feasibility of constructing the Data Mart from routine clinical data. This approach offers a complementary framework for structured RWD extraction and may support future longitudinal analyses and AI-based clinical support in AGHD.
Insulin resistance and sarcopenia: independent and combined associations with obesity and dietary protein intake.
Sajedizadeh M, Bazmi S, Davoudi SH … +3 more , Razaz JM, Farjam M, Homayounfar R
J Endocrinol Invest · 2026 May · PMID 42189481 · Publisher ↗
PURPOSE: To evaluate the independent association between insulin resistance and sarcopenia in adults and to assess whether this relationship differs across sex, age, diabetes status, obesity, and dietary protein intake s...
PURPOSE: To evaluate the independent association between insulin resistance and sarcopenia in adults and to assess whether this relationship differs across sex, age, diabetes status, obesity, and dietary protein intake strata. METHODS: This cross-sectional analysis included 6,670 adults aged 20-70 years from the Monitoring of Metabolic Diseases Risk Factors in Tehran (MMRT) cohort. Sarcopenia was defined as the lowest two population quintiles of skeletal muscle index (SMI) measured via dual-energy X-ray absorptiometry (DXA). Insulin resistance was quantified using the Homeostasis Model Assessment (HOMA-IR). Multivariable logistic regression models adjusted for demographic, lifestyle, socioeconomic, biochemical, and clinical covariates. Subgroup and combined-phenotype analyses were performed by sex, age, diabetes, obesity, and protein intake levels. RESULTS: Sarcopenia prevalence was 39.6%. Participants with sarcopenia were older, had higher BMI and HOMA-IR, and lower physical activity, socioeconomic status, and macronutrient intake. Higher HOMA-IR was associated with 2.64-fold greater odds of sarcopenia (95%CI:2.25-3.10,p < 0.001). Associations persisted across subgroups and were stronger in females (OR = 3.43) than males (OR = 1.47). Insulin-resistant participants with obesity had the highest sarcopenia odds (OR = 4.47), followed by non-obese insulin-resistant individuals (OR = 2.96) and insulin-sensitive individuals with obesity (OR = 1.49). Low protein intake amplified the effect of insulin resistance (OR = 2.92), while higher protein intake partially mitigated risk (OR = 1.81). Mean SMI decreased progressively across HOMA-IR quartiles. CONCLUSION: Insulin resistance is independently and strongly associated with sarcopenia, particularly among females and individuals with obesity. Coexistence of low protein intake and insulin resistance markedly worsens muscle loss, suggesting that targeted metabolic and nutritional interventions may help preserve muscle mass in insulin-resistant populations.
NLRC5 p.Pro191Leu as a genetic susceptibility factor in anti-PIT-1 hypophysitis.
Urai S, Bando H, Yamamoto M … +2 more , Iguchi G, Takahashi Y
J Endocrinol Invest · 2026 May · PMID 42189480 · Publisher ↗
PURPOSE: Anti-PIT-1 hypophysitis is a rare T cell-mediated autoimmune pituitary disorder presenting as a paraneoplastic syndrome or after immune checkpoint inhibitor (ICI) therapy, and its predominance in Japan suggests...
PURPOSE: Anti-PIT-1 hypophysitis is a rare T cell-mediated autoimmune pituitary disorder presenting as a paraneoplastic syndrome or after immune checkpoint inhibitor (ICI) therapy, and its predominance in Japan suggests an underlying genetic predisposition. The NLR family CARD domain containing 5 (NLRC5) encodes a key transcriptional regulator of major histocompatibility complex (MHC) class I, and its p.Pro191Leu missense variant is associated with ICI-related endocrinopathies and enhanced interferon-γ responses. Therefore, we examined whether NLRC5 p.Pro191Leu is enriched in anti-PIT-1 hypophysitis. METHODS: We genotyped the NLRC5 p.Pro191Leu variant (c.572 C > T) in seven Japanese individuals with anti-PIT-1 hypophysitis for whom genomic DNA was available. The carrier frequency observed in this cohort was compared with ancestry-matched expectations from the Tohoku Medical Megabank 61KJPN Japanese reference panel using a prespecified one-sided exact binomial test. Sensitivity analyses included Mid-P adjustment, risk differences, and risk ratios. RESULTS: Among seven genotyped Japanese individuals with anti-PIT-1 hypophysitis, five (71.4%) were carriers, exceeding the expected ancestry-matched frequency from the Japanese reference panel (expected carrier frequency 37.7%; exact p = 0.076; mid-P = 0.045). The effect sizes were risk difference + 0.337 and risk ratio 1.89. CONCLUSION: This study provides suggestive evidence that the NLRC5 p.Pro191Leu variant may confer genetic susceptibility to anti-PIT-1 hypophysitis in the Japanese population, based on its enrichment relative to ancestry-matched reference panels. These findings, together with NLRC5's role as the master regulator of MHC class I expression, propose a novel and testable pathogenic model.
Exploring the dynamics of FGF23 in patients with Hereditary Hemochromatosis type I following iron depletive treatment: a pilot study.
Colangelo L, Terracina S, Sonato C … +13 more , De Martino V, Ferrazza G, Panzini E, Diacinti D, Nieddu L, Arienzo F, Occhiuto M, Cipriani C, Trasarti S, Angeloni A, Pepe J, Corsi A, Minisola S
J Endocrinol Invest · 2026 May · PMID 42189479 · Publisher ↗
PURPOSE: Anemia, inflammation and iron deficiency are linked to Fibroblast growth factor 23 (FGF23). Aim of this study was to explore the dynamics of FGF23 in Hereditary Hemochromatosis type-I (HH1). METHODS: Twenty-six...
PURPOSE: Anemia, inflammation and iron deficiency are linked to Fibroblast growth factor 23 (FGF23). Aim of this study was to explore the dynamics of FGF23 in Hereditary Hemochromatosis type-I (HH1). METHODS: Twenty-six consecutive patients with genetically confirmed and uncomplicated HH1 and nineteen healthy age-matched voluntary blood donors (CTR) were enrolled for the study. Intact (iFGF23) and C-terminal (cFGF23) FGF23 and iron status markers were evaluated at baseline (T0) and seven days (T7) after phlebotomy/voluntary blood donation (VBD). Bone mineral density (BMD) and vertebral fracture assessment (VFA) were also evaluated at T0. RESULTS: Cross-sectional and longitudinal analyses failed to reveal significant differences in iFGF23 in both HH1 (T0: 54.27 ± 14.42 pg/mL; T7: 54.70 ± 15.48 pg/mL) and CTR (T0: 52.77 ± 17.63 pg/mL; T7: 53.27 ± 15.88 pg/mL) groups. Absence of significant difference was also observed for cFGF23 at baseline between the two groups (HH1, T0: 0.98 ± 0.39 pmol/L; CTR, T0: 1.18 ± 0.91 pmol/L) but not at T7 when the values (HH1, T7: 01.20 ± 0.89; CTR, T7: 1.84 ± 1.11 pmol/L) were significantly increased in CTR compared to T0 (p = 0.0003) and to HH1 (p = 0.0240). After phlebotomy/VBD, in both HH1 and CTR groups, serum levels of phosphate were unchanged from baseline while serum iron, ferritin and transferrin saturation and erythrocyte-related parameters (red blood cells, hemoglobin and hematocrit) were significantly reduced (all p < 0.0001). Serum iron, ferritin, and transferrin saturation were significantly higher in HH1 than in CTR (p = 0.0002 for serum iron and p < 0.0001 for both ferritin and transferrin saturation) at T7. In the CTR group, these parameters showed a trend toward iron deficiency whereas in HH1 they remained near the upper limit of the normal range, suggesting a persistent mild iron overload. Correlation and regression analyses did not show significant associations between circulating FGF23 (both iFGF23 and cFGF23) and iron status markers. BMD and VFA were not significantly different between HH1 and CTR. Furthermore, BMD and Trabecular Bone Score values were not associated with circulating FGF23 levels. CONCLUSION: This pilot study indicates that the serum levels of iFGF23 and cFGF23 and skeletal health evaluated through BMD and VFA do not differ between patients with uncomplicated HH1 and healthy subjects at baseline. The absence of changes in the serum levels of iFGF23 and cFGF23 in HH1 patients with uncomplicated HH1 after phlebotomy may reflect the persistence of iron overload which could counteract the physiological hypoxia-driven stimulation of FGF23 production and cleavage observed in healthy subjects after VBD.
Increased risk of urolithiasis in patients with primary aldosteronism: a large-scale retrospective cohort study.
Lee HY, Wang SI, Juan YS … +5 more , Chang CK, Cho SY, Wu WJ, Wu VC, Li WM
J Endocrinol Invest · 2026 May · PMID 42171682 · Publisher ↗
BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with various metabolic disturbances, including calcium metabolism disorders and acid-base imbalances. Emerging e...
BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with various metabolic disturbances, including calcium metabolism disorders and acid-base imbalances. Emerging evidence suggests a potential link between PA and urolithiasis; however, previous studies have been limited by small sample sizes and inconsistent findings. This study aims to investigate the association between PA and urinary stone formation using a large-scale real-world dataset. MATERIALS AND METHODS: We conducted a retrospective cohort study using the TriNetX database, which includes de-identified electronic health records from over 250 million individuals. Patients diagnosed with PA were identified based on ICD-10-CM and ICD-9-CM codes, and a propensity score-matched (PSM) cohort of PA and non-PA patients with hypertension was created. The primary outcome was the incidence of urolithiasis (kidney and urinary tract stones), identified using ICD-10-CM codes (N20-N23). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were conducted based on sex, metabolic disorders, and renal function (eGFR ≥ 60 vs. <60 mL/min/1.73 m²). RESULTS: A total of 10,578 PA patients and 7,897,605 non-PA patients were identified, with 10,577 matched pairs included in the final analysis after 1:1 propensity score matching. PA was associated with a significantly higher risk of urolithiasis compared to non-PA patients at 1-year (HR: 1.524, 95% CI: 1.238-1.877), 3-year (HR: 1.312, 95% CI: 1.120-1.537), 5-year (HR: 1.303, 95% CI: 1.130-1.502), and 7-year (HR: 1.269, 95% CI: 1.107-1.456) follow-ups. Subgroup analyses revealed that the increased risk of urolithiasis persisted across both sexes and was more pronounced in patients without metabolic disorders (HR: 1.826, 95% CI: 1.452-2.295). CONCLUSIONS: Our findings demonstrate a significant association between PA and increased urolithiasis risk, independent of sex. These results highlight the clinical importance of urinary stone screening in patients with PA, particularly those with hypertension or unexplained metabolic abnormalities. Further prospective studies are needed to elucidate the underlying mechanisms and evaluate whether targeted PA treatment could mitigate stone risk in this population.
GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease: mechanistic networks and translational implications: a review.
Wang X, Lu G, Zhou Y … +1 more , Zhao G
J Endocrinol Invest · 2026 May · PMID 42171681 · Publisher ↗
AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and may progress to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatoce...
AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and may progress to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma, yet effective pharmacological therapies remain limited. This review summarizes current evidence on the therapeutic potential and mechanistic basis of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in MASLD. METHODS: We synthesize findings from preclinical models and clinical studies evaluating GLP-1RAs in MASLD/MASH, with emphasis on hepatic metabolic pathways, inflammatory and fibrogenic signaling, and gut-liver axis mechanisms, as well as outcomes from clinical trials and emerging multi-agonist strategies. RESULTS: Clinical studies support the therapeutic relevance of GLP-1RAs in MASLD/MASH by demonstrating reductions in liver fat content, improvements in liver enzyme profiles, and favorable histologic changes, particularly with semaglutide and emerging multi-agonist therapies in selected populations. Preclinical and translational studies further suggest that these benefits may be mediated through integrated effects on hepatic lipid handling, oxidative and inflammatory stress, fibrogenic signaling, and the gut-liver axis, although the relative contribution of direct hepatic versus indirect systemic mechanisms remains incompletely resolved. CONCLUSIONS: Current evidence supports an expanding role for GLP-1-based therapies in metabolic liver disease and provides a mechanistic framework for their continued development and clinical evaluation in MASLD.
Global prevalence of genetic carriers for ARMC5- and KDM1A-associated primary bilateral macronodular adrenal hyperplasia: insights from a large multiethnic genomic database.
Charoenngam N, Wannachalee T
J Endocrinol Invest · 2026 May · PMID 42171680 · Publisher ↗
PURPOSE: To estimate the global prevalence of genetic carriers of primary bilateral macronodular adrenal hyperplasia (PBMAH)-associated variants in ARMC5 and KDM1A using a large genomic database. METHODS: We analyzed seq...
PURPOSE: To estimate the global prevalence of genetic carriers of primary bilateral macronodular adrenal hyperplasia (PBMAH)-associated variants in ARMC5 and KDM1A using a large genomic database. METHODS: We analyzed sequencing data from 807,162 unrelated individuals in gnomAD v4.1. Two prespecified variant-selection strategies were applied. Strict criteria included ARMC5 and KDM1A variants classified as pathogenic/likely pathogenic (P/LP) in ClinVar/LOVD and germline P/LP variants reported in the literature. Liberal criteria included all strict variants plus rare predicted deleterious variants (nonsense, frameshift, loss of start codon and splice-disrupting variants predicted to be deleterious by in silico analysis) and PBMAH-reported somatic ARMC5 variants from the literature as candidate germline susceptibility alleles. Carrier prevalence was estimated by aggregating allele frequencies of qualifying variants overall and by ancestry. RESULTS: For ARMC5, estimated carrier prevalence was 37.5/100,000 under strict criteria and 64.1/100,000 under liberal criteria. Prevalence varied by ancestry, highest in East Asian individuals (strict: 111.4/100,000; liberal: 173.7/100,000) and lowest in Middle Eastern (strict: 0; liberal: 33.0/100,000) and Ashkenazi Jewish groups (strict: 6.8; liberal: 27.0/100,000). For KDM1A, only three variants met strict criteria; liberal criteria yielded an estimated carrier prevalence of 33.8/100,000, highest in Middle Eastern (66.0/100,000) and lowest in Finnish (6.2/100,000). Several variants were enriched in specific ancestries (e.g., ARMC5 p.Arg454Trp in East Asians; ARMC5 p.Arg879Trp and KDM1A p.Arg196AsnfsTer6 in non-Finnish Europeans). CONCLUSION: Population-scale data suggest PBMAH genetic susceptibility due to ARMC5 and KDM1A variants may be more common than implied by clinical series and differs across ancestries, underscoring the need for improved variant curation and phenotype-linked studies.
The impact of type 2 diabetes on male obesity-associated secondary hypogonadism patients undergoing sleeve gastrectomy.
Zhao Y, Cao C, Hua R … +9 more , Tan X, Chu Y, He M, Yao X, Xu B, Shen Q, Fu X, Yao Q, Shao Y
J Endocrinol Invest · 2026 May · PMID 42171679 · Publisher ↗
PURPOSE: Type 2 diabetes mellitus (T2DM) frequently coexists with male obesity-associated secondary hypogonadism (MOSH). This study aims to determine the impacts of T2DM on both baseline features and postoperative outcom...
PURPOSE: Type 2 diabetes mellitus (T2DM) frequently coexists with male obesity-associated secondary hypogonadism (MOSH). This study aims to determine the impacts of T2DM on both baseline features and postoperative outcomes after metabolic bariatric surgery in MOSH patients. METHODS: In this retrospective, two-arm cohort study, patients with MOSH undergoing laparoscopic sleeve gastrectomy (LSG) between January 2021 and June 2025 were stratified by T2DM status and matched 1:1 by age, yielding 174 patients per group. Weight loss, metabolic parameters and sex hormones were assessed at baseline and 12 months post-LSG. RESULTS: Preoperatively, the T2DM group exhibited significantly lower levels of total testosterone (TT) (6.19 vs. 7.13 nmol/L, P < 0.001), free testosterone (FT) (0.16 vs. 0.18 nmol/L, P < 0.05) and bioavailable testosterone (BT) (3.88 vs. 4.27 nmol/L, P < 0.01). Postoperatively, two groups achieved similar weight loss and MOSH remission rates. While TT/FT rose markedly and to similar levels in both groups at 12 months post-LSG (TT: 16.67 vs. 17.09 nmol/L, P = 0.251; FT: 0.34 vs. 0.36 nmol/L, P = 0.195), the T2DM group exhibited persistently lower testosterone bioavailability (BT: 8.28 vs. 8.91 nmol/L, P = 0.013). CONCLUSION: T2DM exacerbates the androgen deficiency in MOSH. Although LSG produces substantial and comparable weight loss, glycemic control, and rises in testosterone across groups, patients with T2DM show incomplete recovery of testosterone bioavailability post-LSG, underscoring the need for targeted postoperative monitoring of androgen bioavailability in this population.
A goitrous woman in 17th-century Andalusia in a painting by Diego Velazquez.
Trimarchi F, Martino E, Bartalena L
J Endocrinol Invest · 2026 May · PMID 42171678 · Publisher ↗
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Reference values for muscle mass and muscle strength: a practical assessment tool for muscle health in Chinese adults.
Lu Z, Hu Y, He H … +2 more , Tu J, Shan G
J Endocrinol Invest · 2026 May · PMID 42171677 · Publisher ↗
PURPOSES: To establish age- and sex-specific percentile reference values for muscle mass and strength in the general population of Chinese adults. METHODS: This study used data from the China National Health Survey, incl...
PURPOSES: To establish age- and sex-specific percentile reference values for muscle mass and strength in the general population of Chinese adults. METHODS: This study used data from the China National Health Survey, including 13,794 adults aged 20-80 years for reference value construction and 3,733 adults for external validation. Muscle mass was assessed by bioelectrical impedance analysis, and muscle strength by a Jamar dynamometer. Sex- and age-specific percentile curves were generated using Generalized Additive Models for Location, Scale, and Shape. RESULTS: In males, whole-body muscle mass index (WMI) increased in early adulthood, peaked in midlife, and declined markedly after 60 years, whereas in females WMI peaked later and declined more gradually. Upper-limb and trunk muscle mass indices showed relatively stable patterns during midlife, while lower-limb muscle mass declined steadily with age in both sexes. Appendicular skeletal muscle mass index remained stable in early adulthood and decreased after midlife. Handgrip strength peaked in midlife in both sexes, and weight-adjusted handgrip strength remained stable until approximately 40 years of age before gradually declining. External validation demonstrated good calibration and consistency of the reference percentiles. CONCLUSIONS: This study provides age- and sex-specific reference values for muscle mass and strength in Chinese adults.
Addison's disease in Italy: mortality and survival by etiology.
Vedolin CK, Sabbadin C, Mondin A … +40 more , Masiero S, Barbot M, Cavedon E, Camozzi V, Mian C, Scaroni C, Presotto F, Garelli S, De Riva C, Delitala A, Radetti G, Longhi S, Giordano C, Guarnotta V, Giordano R, Meloni A, Di Dalmazi G, Pagotto U, Letizia C, Marconcini G, Bogazzi F, Cappa M, Fierabracci A, Crinò A, De Bellis AM, Barrasso M, Falorni A, Morelli V, Perniola R, Pigliaru F, Pivonello R, Simeoli C, Francia G, Salerno C, Capalbo D, Picca G, Stigliano A, Wasniewska MG, Ceccato F, Betterle C
J Endocrinol Invest · 2026 May · PMID 42171676 · Publisher ↗
BACKGROUND: Data on survival and mortality in Addison's disease (AD) are contradictory: some studies suggest a mortality rate two times higher than in the general population, but this is not consistently reported in othe...
BACKGROUND: Data on survival and mortality in Addison's disease (AD) are contradictory: some studies suggest a mortality rate two times higher than in the general population, but this is not consistently reported in other studies. METHODS: We evaluated survival and mortality in 1,826 Italian adult patients with AD of different etiologies, collected from 1947 to 2024 across 30 Endocrine Units. These outcomes were compared to those of the age- and sex-matched Italian reference population using a standardized mortality ratio (SMR) in a subgroup of 1,575 cases. RESULTS: Sex and age adjusted survival analysis showed increased mortality in genetic AD, cancer-related-AD and cases with type 1 autoimmune polyendocrine syndrome (APS-1) compared to other etiologies. The SMR analysis demonstrated a significantly increased mortality risk of the overall patients with AD compared to the general population (SMR 1.34, p < 0.01). However, 4 etiologies presented survival similar to the general population: patients with type 2 or type 4 APS or isolated autoimmune AD (SMR 0.91, p = 0,57), vascular/post-tuberculosis AD (SMR 0.90, p = 0.69), bilateral adrenalectomy due to benign endocrine diseases (SMR 0.91. p = 0.64) and not defined AD (SMR 1.06, p = 0.93). These groups included 1,188 patients, representing 75.4% of the population. On the contrary, a significantly increased mortality risk compared to the general population was reported in the following 3 groups: patients with APS-1 (SMR 5.98, p < 0.01), genetic AD (SMR 5.09, p < 0.01), and cancer-related AD (SMR 4.64, p < 0.01), accounting for 387 patients (24.5%). CONCLUSION: Our study has shown that in adult patients with AD there is a large difference in survival and mortality based on the various etiological forms. In order to evaluate survival and mortality each form of AD must be considered separately and compared with an age- and sex-matched population.
Serum free fatty acid profiles as novel biomarkers for disease activity in Graves' orbitopathy.
Yang X, Liu J, Guo Q … +5 more , Xu Y, Zhao H, Shao J, Liang J, Ye X
J Endocrinol Invest · 2026 May · PMID 42171675 · Publisher ↗
PURPOSE: Graves' orbitopathy (GO) lacks reliable serum biomarkers for objectively evaluating disease activity and severity. In this cross-sectional study, we aimed to investigate alterations in serum free fatty acid (FFA...
PURPOSE: Graves' orbitopathy (GO) lacks reliable serum biomarkers for objectively evaluating disease activity and severity. In this cross-sectional study, we aimed to investigate alterations in serum free fatty acid (FFA) profiles in GO and assess their potential as novel biomarkers. METHODS: We enrolled 60 patients with GO classified by Clinical Activity Score (CAS) and EUGOGO severity. Serum levels of 15 FFAs were measured. Principal component analysis (PCA) visualized group separations. Multivariable logistic regression, adjusted for age, sex, BMI, smoking, TRAb, identified independent predictors. Diagnostic performance was evaluated via ROC analysis, and clinical utility by decision curve analysis (DCA). RESULTS: PCA showed clear separation between active and inactive GO. Active or moderate-to-severe disease was associated with significantly reduced anti-inflammatory FFAs, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), stearidonic acid (FFA18:4), total ω-3, and a lower EPA/AA ratio. After adjustment, decreased EPA/AA ratio (OR = 0.198, 95% CI: 0.051-0.760, p = 0.018) and FFA18:4 (OR = 0.667, 95% CI: 0.464-0.959, p = 0.029) were independent risk factors for active GO. The EPA/AA ratio discriminated active GO with an AUC of 0.847. DCA indicated its strong net clinical benefit across threshold probabilities. CONCLUSION: GO exhibits a distinct serum FFA profile marked by reduced anti-inflammatory fatty acids. The EPA/AA ratio represents a robust, independent biomarker for GO activity, showing great potential for objective clinical assessment and guiding targeted therapy.
Icariin prevents ovariectomy-induced osteoporosis by modulating marrow fatty acid metabolism.
Luo P, Guo M, Jiang L … +6 more , Miao Z, Chen H, Lu L, Zuo X, Nian H, Li G
J Endocrinol Invest · 2026 May · PMID 42171674 · Publisher ↗
PURPOSE: To investigate icariin's regulation of marrow fatty acid metabolism and stearoyl-CoA desaturase (SCD) indices in preventing ovariectomy-induced osteoporosis. METHODS: Thirty-six female Sprague-Dawley rats underw...
PURPOSE: To investigate icariin's regulation of marrow fatty acid metabolism and stearoyl-CoA desaturase (SCD) indices in preventing ovariectomy-induced osteoporosis. METHODS: Thirty-six female Sprague-Dawley rats underwent sham surgery or ovariectomy and were treated with either icariin (125 mg/kg/day) or vehicle via oral gavage for 12 weeks, 6 days per week. Bone marrow was collected from tibias for fatty acid profiling via gas chromatography-mass spectrometry. Serum levels of bone-specific alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were measured using Enzyme-Linked Immunosorbent Assay. Tibial trabecular microstructure was assessed by micro-CT. RESULTS: Ovariectomy significantly altered marrow fatty acid composition, marked by increased palmitic acid (C16:00) and palmitoleic acid (C16:1 n-7), decreased stearic acid (C18:00) and arachidonic acid (C20:4 n-6), and elevated SCD indices. These changes were associated with deteriorated bone microarchitecture and impaired bone turnover. Icariin treatment effectively normalized marrow fatty acid levels, suppressed SCD indices, and consequently attenuated bone loss by improving bone volume fraction, trabecular number, and thickness, while reducing trabecular separation. Additionally, icariin restored the balance of bone turnover markers, increasing BALP and decreasing TRACP-5b. Significant correlations were identified between specific fatty acids and both bone structural parameters and remodeling markers. CONCLUSIONS: Icariin attenuates osteoporotic bone loss by preventing ovariectomy-induced disturbances in marrow fatty acid metabolism, particularly through the suppression of SCD indices and normalization of C16:00, C16:1 n-7, and C18:00 levels. This study highlights the critical role of lipid homeostasis in bone integrity and identifies icariin as a promising lipid-modulating candidate for postmenopausal osteoporosis.
Thyroid abnormalities in acromegaly in the era of improved disease control: a two-stage study.
Diniz Leite LPS, da Rocha BSS, Diniz Leite GAP … +13 more , Diniz Leite GAP, Drumond JB, de O Freitas LG, Freitas IS, Leal ÂC, Santana NO, Lamego Rezende AM, Melo EV, Pereira Oliveira AM, Santps EG, Campos VC, Salvatori R, Aguiar-Oliveira MH
J Endocrinol Invest · 2026 May · PMID 42171673 · Publisher ↗
PURPOSE: Acromegaly is associated with increased risk of diffuse or nodular goiter and possibly of thyroid cancer. The aim of this study was to verify whether these findings persist in the current scenario of improved di...
PURPOSE: Acromegaly is associated with increased risk of diffuse or nodular goiter and possibly of thyroid cancer. The aim of this study was to verify whether these findings persist in the current scenario of improved disease control. METHODS: A two-steps protocol was carried out:. In the first (retrospective), clinical and laboratory data (including 969 IGF-I measurements), and the frequency of thyroid cancer were recorded for 92 acromegaly patients over a 28-year period. The annual control percentage was defined as the average of the ratios between each of the 969 IGF-I measurements over the total follow-up period and the respective upper age limit (IGF-I/ULN) less than 1.Acromegaly activity was determined at the last visit. In the second step (cross-sectional), 74 of the 92 acromegaly patients underwent thyroid ultrasound and were subjected to a two-stage cluster analysis, with the aim of grouping them into homogeneous clusters. RESULTS: 70% of the 92 patients had inactive disease, with a median control rate of 50%, with four cases of thyroid cancer (4.3%), only one in a patient with active disease. Two-thirds of the 74 patients (evaluated by ultrasound) had nodules, and 27% had diffuse thyroid hyperplasia. Three clusters were segregated with high significant differences in sex and echotextural alterations (p < 0.0001 in both cases). Age, number of nodules, thyroid volume and follow-up time were similar between the clusters. CONCLUSION: No inherent thyroid changes were apparently identified in a large cohort of acromegaly patients. Better control during follow-up may attenuate thyroid manifestations in acromegaly.
Changes in cardiometabolic risk factors in transmasculine individuals over 10 years of Gender-Affirming Hormone Therapy.
Azzi M, Lami A, Dones A … +4 more , Cicero AFG, Siconolfi A, Seracchioli R, Meriggiola MC
J Endocrinol Invest · 2026 May · PMID 42171672 · Publisher ↗
PURPOSE: to describe 10-year changes in health measures and cardiovascular risk among transmasculine adults on testosterone-based Gender-Affirming Hormone Therapy. METHODS: this is a single-centre, longitudinal cohort st...
PURPOSE: to describe 10-year changes in health measures and cardiovascular risk among transmasculine adults on testosterone-based Gender-Affirming Hormone Therapy. METHODS: this is a single-centre, longitudinal cohort study of transmasculine adults who began Gender-Affirming Hormone Therapy and were followed-up for a total of 10 years according to standard clinical practice, which includes yearly visits with complete physical examinations, blood tests, and assessment of body composition. For participants aged 35 years or older, we estimated the 10-year cardiovascular risk, and then compared it with age-matched people from the general population. RESULTS: 57 participants completed 10 years of follow-up. Nearly half smoked and few were physically active. Haemoglobin and haematocrit rose early and then stabilised within usual ranges; very high values were uncommon. Fasting glucose, insulin, and blood pressure did not change meaningfully. The lipid profile worsened: LDL, total cholesterol and triglycerides increased, and HDL decreased throughout the study period. Weight, body mass index, waist circumference, and waist-to-hip ratio increased. Body composition showed higher lean mass and trunk fat, with a shift toward android fat distribution. No major cardiovascular events were recorded. One participant developed atrial fibrillation. Metabolic syndrome by female criteria became more frequent. cardiovascular risk was higher than cisgender women but similar to cisgender men at ages 35-44; at ages 45-54 it was lower than cisgender men. CONCLUSIONS: Over 10 years, testosterone-based Gender-Affirming Hormone Therapy is linked to less favorable lipid profiles and body composition patterns, supporting constant monitoring, risk-factor treatment, and lifestyle support.
Cyclic Cushing syndrome as a clinical enigma and diagnostic dilemma in advanced endocrinology.
Ilkiv Y, Potapova K, Yerokhovych V … +1 more , Kobyliak N
J Endocrinol Invest · 2026 May · PMID 42171671 · Publisher ↗
Cyclic Cushing's syndrome (CCS), a rare and atypical form of endogenous hypercortisolism, remains a very relevant problem from a diagnostic point of view. To confirm this disease, it is necessary to record two episodes o...
Cyclic Cushing's syndrome (CCS), a rare and atypical form of endogenous hypercortisolism, remains a very relevant problem from a diagnostic point of view. To confirm this disease, it is necessary to record two episodes of hypercortisolism alternating with period of normocortisolism. Intercyclic phase is characterized not only by negative laboratory test results but also by the absence of pronounced symptoms, making the pathology hidden and, presumably, undiagnosed in certain cases. Some causes remain undetermined and require further investigation. The process of diagnosing and verifying CCS is often lengthy and requires repeated testing at certain intervals. However, none of the currently available methods are 100% accurate. Therefore, a step-by-step approach with confirmation by several highly sensitive tests is recommended for the differential diagnosis of ACTH-dependent and ACTH-independent cyclic hypercortisolism. The risk of false results cannot be ruled out even when the most reliable methods available today are used. Thus, the diagnostic algorithm for each individual case will be specific and will depend on the phase of the disease, the patient's condition, and concomitant pathology. Our review summarizes current data on the mechanisms of cyclic hypercortisolism known to date and provides a comparative and critical analysis of modern diagnostic methods that help identify this pathology and indicate its origin.
The impact of mineralocorticoid receptor antagonists on fat mass and fat metabolism.
Afsar B, Afsar RE, Maddukuri G
J Endocrinol Invest · 2026 May · PMID 42171670 · Publisher ↗
INTRODUCTION: Obesity is a chronic, multifactorial condition which is a global health challenge. In general, obesity is defined by excessive fat accumulation and associated with the risk of numerous conditions, including...
INTRODUCTION: Obesity is a chronic, multifactorial condition which is a global health challenge. In general, obesity is defined by excessive fat accumulation and associated with the risk of numerous conditions, including type 2 diabetes mellitus (T2DM), cardiovascular disease, heart failure, and metabolic dysfunction-associated steatotic liver disease, and some types of cancer contributing to increased morbidity and mortality. Mineralocorticoid receptor antagonists (MRAs) are used for a long time for management of cardiovascular disease and non-steroidal MRAs also showed kidney protection. Apart from these, there is growing literature showing that MRAs effecting fat mass and fat metabolism. In this review, we summarised the effects of MRAs on fat mass and fat metabolism. RESULTS: In general, studies showed that MRAs reduced fat mass in various organs which is associated decreased oxidative stress, inflammation, and insulin resistance. Importantly, MRAs increased adipose tissue browning and decrease white adipose tissue mass. Up to now, the studies showed no safety signals and these favorable effects are independent of blood pressure reduction. Discussion A part from hemodynamic effects, MRAs have beneficial impacts on fat mass and fat metabolism. Currently, the underlying mechanisms for these effects are not clear Conclusions: Preliminary studies have shown that MRAs have favorable impact on fat metabolism and fat mass. Studies needed to highlight underlying mechanisms..
Dyslipidemias associated with endocrine disorders: a position statement of the working group of the nutrition hormones and metabolism club of the italian society of endocrinology (SIE).
Muscogiuri G, Albertelli M, Arnaldi G … +30 more , Barrea L, Bellastella G, Bonomi M, Caputo M, Caprio M, Cignarelli A, Di Gioia L, Frasca F, Ferrari D, Gambineri A, Gasco V, Gatto F, Giandalia A, Giordano R, Infante M, Isidori A, Malandrino P, Occhi G, Pivonello R, Prencipe N, Prodam F, Simeoli C, Verde L, Vignozzi L, Cannavò S, Giorgino F, Colao A, Aimaretti G, Ferone D, Perrini S
J Endocrinol Invest · 2026 May · PMID 42171669 · Publisher ↗
PURPOSE: Dyslipidemias are highly prevalent metabolic disturbances and represent a major driver of atherosclerotic cardiovascular disease. Beyond primary forms, numerous endocrine diseases induce secondary dyslipidemias...
PURPOSE: Dyslipidemias are highly prevalent metabolic disturbances and represent a major driver of atherosclerotic cardiovascular disease. Beyond primary forms, numerous endocrine diseases induce secondary dyslipidemias that substantially modify lipid metabolism and contribute to cardiometabolic risk. This Position Statement of the Nutrition Hormones and Metabolism Club of the Italian Society of Endocrinology (SIE) aims to provide an updated, evidence-based synthesis of the pathophysiology, biochemical profile, and clinical impact of dyslipidemias associated with endocrine disorders. METHODS: A comprehensive review of current literature was performed, integrating epidemiological, mechanistic, and clinical data on lipid alterations across major endocrine diseases. Expert consensus was used to interpret evidence and formulate recommendations for clinical practice. RESULTS: Distinct and disease-specific dyslipidemic patterns were identified across conditions involving the hypothalamic-pituitary, thyroid, adrenal, gonadal, and GH/IGF-1 axes. Disorders such as acromegaly, growth hormone deficiency, hypothyroidism, hyperthyroidism, Cushing's syndrome, male and female hypogonadism, congenital adrenal hyperplasia, and polycystic ovary syndrome exhibit characteristic lipid abnormalities driven by hormonal dysregulation. These alterations contribute to increased cardiometabolic risk yet are frequently underrecognized and suboptimally managed. Early identification and tailored intervention may significantly improve outcomes. CONCLUSION: Endocrine-related dyslipidemias represent a clinically relevant but often overlooked contributor to cardiovascular risk. By summarizing current evidence and expert perspectives, this Position Statement aims to support clinicians in improving diagnosis, risk stratification, and management of lipid disorders associated with endocrine diseases, fostering a multidisciplinary approach to cardiometabolic prevention.
Beyond MRI: Unveiling metabolic signatures of primary hypophysitis with F-FDG PET.
Sahin S, Kocaman BB, Yanmaz MU … +8 more , Biyikoglu SE, Korkmaz OP, Durcan E, Asa S, Sayman HB, Ozkaya HM, Tanriover N, Kadioglu P
J Endocrinol Invest · 2026 May · PMID 42171668 · Publisher ↗
AIMS: Hypophysitis is a heterogeneous clinical entity originating from different anatomical compartments of the pituitary gland and driven by diverse pathophysiological mechanisms. This study aims to explore the potentia...
AIMS: Hypophysitis is a heterogeneous clinical entity originating from different anatomical compartments of the pituitary gland and driven by diverse pathophysiological mechanisms. This study aims to explore the potential diagnostic and clinical value of F-fluorodeoxyglucose positron emission tomography in the evaluation of primary hypophysitis. MATERIALS AND METHODS: This single-center retrospective study was conducted at the pituitary referral unit of a tertiary university hospital. The study population included patients with primary hypophysitis, individuals with nonfunctioning pituitary adenomas, and subjects without intracranial pathology. Demographic features, baseline clinical and biochemical characteristics, as well as initial cranial and sellar magnetic resonance imaging and F-fluorodeoxyglucose positron emission tomography findings, were systematically analyzed and compared across groups. Furthermore, in the primary hypophysitis subgroup, potential associations between positron emission tomography imaging parameters and clinical, radiological, and laboratory characteristics were specifically examined. RESULTS: A total of 46 participants were enrolled in the study, comprising 16 patients with primary hypophysitis, nine with nonfunctioning pituitary adenoma, and 21 controls without intracranial pathology. Positron emission tomography demonstrated significantly higher maximum and mean standardized uptake values in patients with primary hypophysitis compared with controls, whereas no significant differences were observed between the other groups. Within the primary hypophysitis cohort, mean standardized uptake values were significantly elevated in patients with hypopituitarism and in those with Arginine vasopressin deficiency (central diabetes insipidus) compared to their respective counterparts without these conditions. Furthermore, both maximum and mean standardized uptake values were markedly higher in patients with growth hormone deficiency than in those with preserved growth hormone function. CONCLUSION: These findings suggest that metabolic activity observed on F-fluorodeoxyglucose positron emission tomography may serve as a marker of disease severity and pituitary dysfunction in primary hypophysitis.
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