Endocrine最新文献

{"title":"Association of ADAM17 expression with CD4 + and CD8 + tumor-infiltrating lymphocytes in adrenocortical carcinoma and benign adrenal adenoma.","authors":"Mehmet Sözen, Seda Duman Öztürk, Alev Selek, Berrin Çetinarslan, Zeynep Cantürk, Emre Gezer, Sibel Balcı","doi":"10.1007/s12020-026-04764-8","DOIUrl":"10.1007/s12020-026-04764-8","url":null,"abstract":"<p><strong>Background: </strong>Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy. Although immune checkpoint signaling and tumor-infiltrating lymphocytes (TILs) have been implicated in ACC biology, the role of ADAM10 and ADAM17 in the adrenocortical tumor immune microenvironment remains poorly understood. This study aimed to evaluate the expression of ADAM10, ADAM17, PD-L1, CD4, and CD8 in ACC and benign adrenal adenoma (BAA) tissues.</p><p><strong>Methods: </strong>This retrospective study included 21 patients with histopathologically confirmed ACC and 39 patients with BAA. Immunohistochemical staining for ADAM10, ADAM17, PD-L1, CD4, and CD8 was performed on formalin-fixed paraffin-embedded tissue samples. ADAM10 and ADAM17 expression were assessed using H-scores, while CD4 + and CD8 + TIL counts were quantified by cell counting. Comparative and correlation analyses were conducted.</p><p><strong>Results: </strong>ACC tissues exhibited significantly higher CD4 + and CD8 + TIL counts than BAA tissues (p = 0.010 and p = 0.006, respectively). No significant differences were observed between the groups regarding ADAM10, ADAM17, or PD-L1 expression (all p > 0.05). ADAM17 H-scores showed significant positive correlations with both CD4 + and CD8 + TIL counts in ACC and BAA. No significant associations were found between ADAM10, ADAM17, or PD-L1 expression and Ki-67 index, tumor size, or ENSAT stage.</p><p><strong>Conclusions: </strong>In this cohort, ACC tissues showed higher CD4 + and CD8 + TIL counts than BAA tissues. Although ADAM10, ADAM17, and PD-L1 expression did not differ significantly between malignant and benign tumors, ADAM17 expression was positively associated with TIL count. These findings warrant further investigation of the potential relationship between ADAM17 and the immune microenvironment of adrenocortical tumors.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational weight loss relative to prepregnancy weight in women with gestational diabetes: impact on maternal and neonatal outcomes.","authors":"Filipa Sales Moreira, Maria Luís Mazeda, Bruna Silva, Ana Saavedra, Catarina Cidade-Rodrigues, Catarina Chaves, Vânia Benido-Silva, Vânia Gomes, Catarina A Pereira, Cláudia Machado, Odete Figueiredo, Anabela Melo, Mariana Martinho, Anabela Ferreira, Ana Morgado, Maria Céu Almeida, Margarida Almeida, Filipe M Cunha","doi":"10.1007/s12020-026-04768-4","DOIUrl":"10.1007/s12020-026-04768-4","url":null,"abstract":"<p><strong>Purpose: </strong>Gestational weight loss (GWL) of overweight or obese women with gestational diabetes (GDM) during the third trimester has been associated with lower risk of macrosomia, caesarean delivery (CS) or neonatal intensive care unit (NICU) admission but with higher risk of preterm delivery (PTD) and small-for-gestational-age (SGA). We studied the association between GWL during the whole pregnancy and perinatal outcomes.</p><p><strong>Methods: </strong>We conducted a retrospective study of the Portuguese national GDM database including all women with singleton pregnancies diagnosed by 24-28 week OGTT (oral glucose tolerance test) who delivered a liveborn infant and had recorded perinatal outcomes and gestational weight change. GWL was defined as weight loss between the maternal weight at delivery and pregestational weight.</p><p><strong>Results: </strong>Among 7768 women, 180 (2.3%) had GWL; they had higher BMI, more frequent family history of type 2 diabetes, previous GDM, chronic hypertension, multiparity, higher fasting OGTT glucose and more frequent metformin treatment than women without GWL. GWL was associated with higher odds of PTD (OR 2.35, 95%CI 1.40-3.97, p- value = 0.001) and SGA (2.71, 1.70-4.33, p-value < 0.001) and lower odds of CS (0.62, 0.44-0.88, p-value = 0.006) and LGA (0.40, 0.22-0.70, p-value = 0.002), with non significant associations for HDP, NH, RDS and NICU admission.</p><p><strong>Conclusion: </strong>GWL was uncommon among women with GDM and was associated with over 2.3-fold higher risk of PTD, 2.7-fold higher risk of SGA newborns, and a 48% lower risk of CS and 60% lower risk of LGA infants.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation and potential overuse in thyroid ultrasound ordering: exploratory insights from a clinician survey.","authors":"Sualeha Khalid, Alexandria Ratzki-Leewing, Juan P Brito, Naykky Singh Ospina, Rozalina G McCoy","doi":"10.1007/s12020-026-04742-0","DOIUrl":"10.1007/s12020-026-04742-0","url":null,"abstract":"<p><strong>Purpose: </strong>Increasing use of thyroid ultrasound has contributed to the overdiagnosis of low-risk thyroid cancer which has in turn led to overtreatment as well. Despite established guidelines, deviations from evidence-based use persist. We evaluated clinician-reported practices, knowledge, and perceptions regarding thyroid ultrasound ordering.</p><p><strong>Methods: </strong>We conducted a pilot, exploratory, cross-sectional survey of clinicians at the University of Maryland Medical System. A 21-item electronic questionnaire assessed guideline familiarity, ordering practices, and perceived drivers of thyroid ultrasound use. The survey was distributed to internal medicine, family medicine, and endocrinology trainees, advanced practice providers, and faculty.</p><p><strong>Results: </strong>Thirty clinicians responded (43% internal medicine (IM), 40% endocrinology, 13% family medicine (FM), 3% IM and FM). One-third reported ordering 1-5 thyroid ultrasounds annually, while 20% reported ordering more than 50. Although 50% believed diagnostic testing improves outcomes, 47% perceived thyroid ultrasound as overused. Ordering was most driven by physical exam findings, compressive symptoms, and incidental nodules, rather than demographic factors or screening. Familiarity with American Thyroid Association guidelines exceeded that of American College of Radiology guidelines. Only 62% reported confidence in their own knowledge regarding thyroid ultrasound ordering.</p><p><strong>Conclusion: </strong>Clinicians recognize potential overuse of thyroid ultrasound, driven by multi-factorial influences. Gaps in familiarity and confidence may contribute to practice variation, highlighting opportunities for targeted interventions to promote high-value care.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management and safety of somatostatin receptor ligands and pegvisomant in pregnant women with acromegaly: a narrative review of the literature.","authors":"Margherita Medici, Valentino Marino Picciola, Irene Comune, Alessandro Cicale, Maria Chiara Zatelli, Maria Rosaria Ambrosio","doi":"10.1007/s12020-026-04761-x","DOIUrl":"10.1007/s12020-026-04761-x","url":null,"abstract":"<p><strong>Purpose: </strong>Pregnancy in acromegaly is a rare event. Its management is still a challenge given the lack of data, the risk of tumor progression and maternal-fetal complications. This study aims to evaluate the impact of different treatment strategies, particularly somatostatin receptor ligands (SRL) and pegvisomant (PEG), on maternal and neonatal outcomes through a comprehensive review of the literature.</p><p><strong>Methods: </strong>We performed a narrative review of the literature. A PubMed search was performed using the keywords \"acromegaly AND pregnancy\", combined with treatment-related terms, covering publications from January 1, 1988, to January 21, 2026. No publication type restrictions were applied. Additional articles were identified through manual reference screening. Articles published in English and Italian were included.</p><p><strong>Results: </strong>A total of 44 articles were identified, comprising 120 patients and 134 pregnancies; we further contribute an additional case of pregnancy with pasireotide exposure, representing the third reported case of pasireotide exposure during pregnancy. Medical management was categorized as follows: treatment withdrawal before conception (n = 40), discontinuation upon pregnancy confirmation (n = 47), and continuation or modification throughout gestation (n = 30). Symptom worsening occurred in 16.7-40%. Maternal complications included gestational diabetes (5.6-18.8%) and pre-eclampsia (2.8-10.3%). Overall, fetal outcomes were favorable, with only one congenital malformation. Breastfeeding was successfully achieved in most cases.</p><p><strong>Conclusion: </strong>Pregnancy in acromegaly is generally characterized by clinical stability, supporting the safety of treatment withdrawal upon conception in most patients. While early therapy discontinuation is standard, SRL and/or PEG treatment is a viable option for patients requiring tumor and biochemical control. Individualized multidisciplinary management is essential.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World safety, patient-reported outcomes, and glycemic metrics with a 7-Day extended infusion set in adults with Type 1 diabetes using automated insulin delivery systems.","authors":"María de la O Nieto de la Marca, Pablo Fernández Velasco, Sofía Del Amo Simón, Marta Sánchez Ibáñez, Ana Collantes Matallana, Emilia Gómez Hoyos, Beatriz Torres Torres, Ana Ortolá Buigues, Daniel Antonio de Luis Román, Gonzalo Díaz Soto","doi":"10.1007/s12020-026-04743-z","DOIUrl":"10.1007/s12020-026-04743-z","url":null,"abstract":"<p><strong>Background: </strong>Extended-wear infusion sets (E-iS) allowing up to 7 days of catheter use have recently become available. Real-world evidence of contemporary automated insulin delivery (AID) systems using E-iS remains limited.</p><p><strong>Method: </strong>A prospective non-randomized single-arm real-world study in adults with type 1 diabetes using the MiniMed-780G AID system who transitioned from conventional 3-day infusion sets to E-iS was conducted. Clinical variables, device settings, adverse events, and patient-reported outcomes were assessed at baseline, 3 and 6 months.</p><p><strong>Results: </strong>65 participants were included, 58 completed 6 months of follow-up.Mean catheter wear time increased from 3.6 ± 1.1 to 6.1 ± 2.3 days,(p < 0.001), and reservoir change interval increased from 3.5 ± 1.0 to 5.2 ± 2.3 days,(p < 0.001). Glycemic control remained overall stable, although small changes were observed in some CGM metrics (Time in range-TIR: 80.0 ± 7.1% to 78.0 ± 10.0%, p = 0.014) and slight increases in time above range, while hypoglycemia exposure remained unchanged. HbA1c decreased from 6.8 ± 0.5% to 6.4 ± 1.0%, (p = 0.03). Total daily insulin dose did not change, but insulin use related to infusion set management decreased significantly. Pain at cannula insertion improved from 2.1 ± 1.5 to 1.2 ± 1.1,(p < 0.001), and treatment satisfaction increased from 8.2 ± 1.9 to 9.0 ± 1.2,(p = 0.012). No episodes of severe hypoglycemia or diabetic ketoacidosis occurred. Cannula wear duration was strongly correlated with reservoir change interval (r = 0.712, p < 0.001). At 6 months, 92.3% of participants continued using the E-iS, with 48.3% maintaining the full 7-day wear duration.</p><p><strong>Conclusions: </strong>In real-world use with an AID system, the E-iS significantly prolonged catheter wear duration and reservoir change intervals while remaining safe and well tolerated. It was associated with high satisfaction and stable glycemic outcomes, supporting E-iS as a practical strategy to reduce the burden of infusion set changes in routine clinical practice.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for immune checkpoint inhibitor-related thyroid dysfunction: a retrospective cohort study.","authors":"Takahiro Amemiya, Hiroshi Suzuki","doi":"10.1007/s12020-026-04758-6","DOIUrl":"10.1007/s12020-026-04758-6","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies; however, the high incidence of immune-related adverse events, including thyroid dysfunction, is a major clinical concern. Thyroid dysfunction occurs frequently, affects patient health and quality of life, and can be life-threatening when severe, necessitating prompt identification and management. Herein, we aimed to identify pretreatment risk factors associated with ICI-induced thyroid dysfunction.</p><p><strong>Methods: </strong>Medical records of patients administered ICIs were retrospectively reviewed. Data on patient age, sex, and body weight; primary tumor type; ICI agent; programmed death-ligand 1 status; disease stage; line(s) of treatment; and laboratory parameters measured before treatment initiation were extracted. These characteristics were compared between patients who developed thyroid dysfunction and those who did not.</p><p><strong>Results: </strong>An elevated pretreatment eosinophil count was significantly associated with thyroid dysfunction following ICI therapy. In the multivariable logistic regression analysis, eosinophil count remained significantly associated with thyroid dysfunction after adjustment for lactate dehydrogenase (LDH; adjusted odds ratio per 0.1 × 10³/µL increase, 2.18; 95% confidence interval [CI], 1.56-3.04; P < 0.001). Receiver operating characteristic analysis yielded an area under the curve of 0.812 (95% CI, 0.722-0.902). The optimal cutoff value was 0.2 × 10³/µL, with a sensitivity of 81.0% and a specificity of 68.2%.</p><p><strong>Conclusion: </strong>An elevated pretreatment eosinophil count was associated with subsequent thyroid dysfunction following ICI therapy after adjustment for LDH. Further prospective studies incorporating thyroid autoantibody status are required to determine its clinical utility as a candidate marker.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of inadequately controlled hypothyroidism with major adverse cardiovascular events in type 2 diabetes patients receiving levothyroxine: a retrospective cohort study.","authors":"Yi-Hsuan Lin, Chih-Wei Hsu, Pi-Hua Liu, Yu-Yao Huang, Chia-Hung Lin","doi":"10.1007/s12020-026-04651-2","DOIUrl":"10.1007/s12020-026-04651-2","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate whether levothyroxine (LT4) therapy is associated with major adverse cardiovascular events (MACE) in adults with type 2 diabetes.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the multi-institutional Chang Gung Research Database (2006-2017). New LT4 users were direct covariate matching with a 1:1 ratio to nonusers by age, sex, and index date, excluding patients with prior LT4 exposure or prior MACE. The primary outcome was MACE-nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization-with follow-up from the index date to the first event or 31 December 2017. Baseline comorbidities, concomitant medications, and laboratory parameters were assessed; Cox models estimated hazard in the matched cohort. Prespecified subgroup analyses examined age, sex, hypertension, diabetic microvascular complications, and end-stage renal disease.</p><p><strong>Results: </strong>Compared with matched nonusers, LT4 users had a higher incidence of MACE, with higher rates of nonfatal stroke and heart failure hospitalization. In subgroup analyses, LT4 use, older age, male sex, hypertension, diabetic microvascular complications, and end-stage renal disease were associated with increased MACE risk.</p><p><strong>Conclusion: </strong>In adults with type 2 diabetes, the increased risk of MACE observed in patients receiving LT4 appears to be driven by inadequately controlled hypothyroidism rather than the medication itself. These findings underscore the critical importance of achieving and maintaining euthyroidism through careful LT4 dosing and active thyroid-function monitoring to mitigate cardiovascular risk in this high-risk population.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined use of SGLT2 inhibitor and GLP-1 receptor agonist versus either monotherapy for cardiorenal Outcomes: an exploratory network meta-analysis of 16 randomized trials.","authors":"Mainak Banerjee, Madhurima Basu, Pradip Mukhopadhyay, Sujoy Ghosh","doi":"10.1007/s12020-026-04752-y","DOIUrl":"10.1007/s12020-026-04752-y","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) each provide cardiorenal protection in trials of selected populations, but their combined effect has not been tested in dedicated head-to-head randomized trials. We performed an exploratory network meta-analysis (NMA) that integrated subgroup data from existing randomized controlled trials (RCTs) to compare SGLT2i, GLP-1RA, and concomitant SGLT2i + GLP-1RA use against placebo on cardiorenal outcomes.</p><p><strong>Methods: </strong>We ran a frequentist random-effects NMA. Major databases were searched for RCTs or post-hoc analyses (> 1 year follow-up) that reported subgroup outcomes by background SGLT2i or GLP-1RA use. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were hospitalisation for heart failure (HHF), composite renal outcomes, and total estimated glomerular filtration rate (eGFR) slope. Surface Under the Cumulative Ranking Curve (SUCRA) values are reported as supportive ranking summaries.</p><p><strong>Results: </strong>Sixteen RCTs were pooled. Compared with placebo (without background SGLT2i or GLP-1RA), all active strategies reduced MACE and HHF (all p < 0.05). For composite renal events, combined use (RR 0.63, 95% CI 0.41-0.97) and SGLT2i (RR 0.70, 95% CI 0.61-0.79) significantly reduced risk. Combined use ranked first across outcomes (SUCRA 0.928 to 1.000). In head-to-head pooled comparisons, combined use was associated with lower MACE (RR 0.83, 95% CI 0.72-0.96) and HHF (RR 0.73, 95% CI 0.56-0.94) than SGLT2i alone, and with a better total eGFR slope than GLP-1RA alone (MD + 2.29 mL/min/1.73 m2/year, 95% CI 0.14-4.44). A subgroup NMA showed attenuated MACE ranking for combined use in ASCVD or high-ASCVD-risk trials, although the HHF ranking was preserved.</p><p><strong>Conclusion: </strong>In this exploratory synthesis, concomitant SGLT2i and GLP-1RA use appeared to be associated with more favourable cardiorenal effects than either agent alone. Because the combined-use comparison rests largely on non-randomized within-trial subgroups, these findings are hypothesis-generating and require confirmation in dedicated head-to-head randomized trials of combination therapy.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital goitrous hypothyroidism due to thyroglobulin deficiency associated with angioinvasive follicular thyroid carcinoma: comprehensive and integral analysis of the p.Cys1897_Glu1900 deletion.","authors":"Valeria F Garzón, Jéssica López Marti, Mauricio Gomes Pio, Juan M Lazzati, Jorge Zappa, Wanderson Marques da Silva, Noelia Dujovne, Carina M Rivolta, Héctor M Targovnik","doi":"10.1007/s12020-026-04746-w","DOIUrl":"10.1007/s12020-026-04746-w","url":null,"abstract":"<p><strong>Purpose: </strong>This study focused on elucidating the molecular basis underlying the clinical phenotype of a patient presenting with congenital hypothyroidism (CH), goiter, and angioinvasive follicular thyroid carcinoma.</p><p><strong>Methods: </strong>The index patient underwent comprehensive clinical, biochemical, and imaging assessments. DNA sequencing, genotyping, and bioinformatics analyses were subsequently performed.</p><p><strong>Results: </strong>Whole exome sequencing (WES) of peripheral blood leukocyte and tumor tissue DNA, together with confirmatory Sanger sequencing, revealed a previously undescribed homozygous inactivating thyroglobulin (TG) variant, NM_003235.5:c.5688_5699delTTGTGTGCAGGA [NP_003226.4:p.Cys1897_Glu1900del]. Family segregation analysis demonstrated that the healthy mother and half-sister were heterozygous carriers of the NM_003235.5:c.5688_5699del variant, while paternal DNA was not available for sequence analysis. The deletion occurs immediately after the first nucleotide of exon 31, within the TG type 3a-2 domain of region III, removing 12 nucleotides that encode the amino acids cysteine¹⁸⁹⁷-valine¹⁸⁹⁸-glutamine¹⁸⁹⁹-glutamic acid¹⁹⁰⁰. Although the deletion does not cause a frameshift, the loss of cysteine¹⁸⁹⁷ disrupts a critical disulfide bond, thereby altering the three-dimensional structure of TG. DECoN software analysis of WES data confirmed the homozygous state in the index patient, with no evidence of allelic deletion or duplication in the TG locus on chromosome 8. Single-nucleotide variant (SNV) and indel analysis across chromosome 8 identified a continuous homozygous block of approximately 17.7 Mb encompassing the TG gene, supporting an interpretation consistent with either segmental terminal uniparental isodisomy or a copy neutral loss of heterozygosity arising from recombination. Despite an extensive evaluation of 69 additional candidate genes involved in thyroid physiology, regulatory mechanisms, and the pathogenesis of primary and central CH and goiter, together with 43 genes within pathways recognized for their role in cancer progression and major drivers of thyroid tumorigenesis-using population databases and predictive tools for non synonymous missense variants-no deleterious variants were identified in any of these genes.</p><p><strong>Conclusion: </strong>We report a novel deletion that broadens the spectrum of TG variants. This defect impairs T₄ synthesis, elevates TSH levels, and-through its mitogenic effect-drives goiter development, while potentially predisposing to angioinvasive follicular thyroid carcinoma.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148800455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical management challenges of Cushing's disease associated with double pituitary adenomas: four cases and literature review.","authors":"Di Zhang, Wan Su, Jinghua Liu, Siti Liu, Yuchen Wei, Hui You, Bo Hou, Xinxin Mao, Yi Zhang, Kan Deng, Jifang Liu, Yong Yao, Lin Lu","doi":"10.1007/s12020-026-04748-8","DOIUrl":"10.1007/s12020-026-04748-8","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize clinical, radiological, and pathological features of double pituitary adenomas (DPAs) involving a corticotroph adenoma and evaluate challenges associated with preoperative localization and surgical management of Cushing's disease (CD).</p><p><strong>Methods: </strong>We retrospectively reviewed four institutional cases and searched PubMed and Web of Science (1990-2025), identifying 30 publications comprising 68 additional cases. Demographic, clinical, radiological, immunohistochemical, surgical, and outcome data from the combined cohort were analyzed.</p><p><strong>Results: </strong>In all four institutional cases, the lesion removed during initial transsphenoidal surgery (TSS) was a noncorticotroph adenoma, and hypercortisolism persisted. Follow-up pituitary magnetic resonance imaging (MRI) demonstrated a second suspected lesion in all four patients. In Cases 3 and 4, MRI abnormalities were subtle or equivocal, and ⁶⁸Ga-pentixafor positron emission tomography/computed tomography (PET/CT) revealed concordant focal uptake at the suspected sites. Revision TSS confirmed an adrenocorticotropic hormone (ACTH)- and T-PIT-positive corticotroph adenoma in all four patients, and all achieved early postoperative biochemical remission. In the combined cohort (72 patients), preoperative MRI identified both lesions in 12 patients (16.7%) and only one lesion in 39 (54.2%); MRI findings were unavailable or insufficiently described in 21 (29.2%). Sixteen patients (22.2%) underwent repeat surgery, whereas surgical-course information was unavailable in 21 (29.2%).</p><p><strong>Conclusions: </strong>DPAs involving a corticotroph component should be considered as a possible explanation for persistent hypercortisolism after TSS when the resected lesion is negative for ACTH and T-PIT. Multidisciplinary reassessment and repeat expert pituitary imaging review may help identify an additional lesion. The role of adjunctive molecular imaging remains preliminary.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":"91 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}