Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Predictors of cardiovascular disease in individuals with dysbetalipoproteinemia: a prospective study in the UK Biobank.","authors":"Martine Paquette, Mark Trinder, Simon-Pierre Guay, Liam R Brunham, Alexis Baass","doi":"10.1210/clinem/dgae618","DOIUrl":"https://doi.org/10.1210/clinem/dgae618","url":null,"abstract":"<p><strong>Background: </strong>Dysbetalipoproteinemia (DBL) is a disorder of remnant cholesterol metabolism associated with a severe risk of atherosclerotic cardiovascular disease (ASCVD).</p><p><strong>Objective: </strong>The objective of this study was to investigate the univariate and multivariate predictors of ASCVD in individuals with DBL.</p><p><strong>Methods: </strong>Data from 2,699 individuals with ε2/ε2 genotypes from the UK Biobank were included in this study. DBL was defined as having an ε2ε2 genotype with evidence of dyslipidemia, defined as total cholesterol ≥ 200 mg/dL [5.2 mmol/L] and TG ≥ 175 mg/dL [2.0 mmol/L]) or lipid-lowering therapy use (n=964).</p><p><strong>Results: </strong>Age, hypertension, waist circumference and a polygenic risk score for coronary artery disease (PRSCAD) were independent predictors of ASCVD among individuals with DBL. Cumulative ASCVD-free survival was lower in the ε2/ε2 DBL group (84%) compared to the ε2/ε2 non-DBL group (94%) (p<0.0001), and for DBL individuals with a PRSCAD ≥ median (79%) compared to those with a PRSCAD < median (89%) (p=0.001).</p><p><strong>Conclusion: </strong>We show in a large prospective cohort that a PRSCAD predicts the ASCVD risk among individuals with DBL. The findings of the present study highlight the need for better risk stratification in ε2/ε2 carriers to identify high risk individuals that would need aggressive cardiovascular management despite their low apolipoprotein B value.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposed Denosumab Biosimilar SB16 vs Reference Denosumab in Postmenopausal Osteoporosis: Phase 3 Results Up to Month 12.","authors":"Bente Langdahl, Yoon-Sok Chung, Rafal Plebanski, Edward Czerwinski, Eva Dokoupilova, Jerzy Supronik, Jan Rosa, Andrzej Mydlak, Anna Rowińska-Osuch, Ki-Hyun Baek, Audrone Urboniene, Robert Mordaka, Sohui Ahn, Young Hee Rho, Jisuk Ban, Richard Eastell","doi":"10.1210/clinem/dgae611","DOIUrl":"https://doi.org/10.1210/clinem/dgae611","url":null,"abstract":"<p><strong>Context: </strong>SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia).</p><p><strong>Objective: </strong>This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (PMO; NCT04664959).</p><p><strong>Design: </strong>The study included 457 PMO patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at Month 0 and Month 6. At Month 12, patients were re-randomized to continue with the assigned treatment or switch from DEN to SB16 up to Month 18. This report includes results up to Month 12.</p><p><strong>Methods: </strong>The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for Month 12), total hip and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen [CTX] and procollagen type I N-terminal propeptide [P1NP]), safety, and immunogenicity profiles were measured up to Month 12.</p><p><strong>Results: </strong>The least-squares mean differences in percent change from baseline in lumbar spine BMD at Month 12 were 0.33% (90% confidence interval [CI]: -0.25, 0.91) in the full analysis set and 0.39% (95% CI: -0.36, 1.13) in the per-protocol set; both within the pre-defined equivalence margin. The secondary endpoints were comparable between the two treatment groups.</p><p><strong>Conclusion: </strong>The reported efficacy, PK, PD, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Activating ESR1 Mutation in an Aggressive Prolactinoma.","authors":"Ticiana Paes, Jacobo Buelvas Mebarak, John C Magnotto, George A Stamatiades, Yanan Kuang, Cloud Paweletz, Edward R Laws, Natalie Grosek, Rona S Carroll, Rinath Jeselsohn, Dipika R Mohan, Antonio Marcondes Lerario, Minh T Truong, Wenya Linda Bi, David A Reardon, David M Meredith, Ursula B Kaiser, Ana Paula Abreu","doi":"10.1210/clinem/dgae615","DOIUrl":"https://doi.org/10.1210/clinem/dgae615","url":null,"abstract":"<p><strong>Context and objective: </strong>The genetic profile of prolactinomas remains poorly understood. Our objective is to identify somatic genetic alterations associated with prolactinomas and to report the identification of an activating ESR1 mutation (ESR1Y537S) in an aggressive prolactinoma.</p><p><strong>Setting: </strong>Brigham and Women's Hospital.</p><p><strong>Design: </strong>Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation (CNV).</p><p><strong>Results: </strong>Twenty subjects (mean age 38.6 years; 12 women and 8 men) were included in this study. A somatic ESR1Y537S mutation was identified in an aggressive prolactinoma in a post-menopausal woman. No SF3B1 or other somatic mutations were identified. The median number of CNV events identified in our samples was 46; the prolactinoma with ESR1Y537S had the highest number with 233 events. In breast cancer, ESR1Y537S has been shown to activate estrogen receptor alpha independent of ligand binding. In patients with resistant breast cancer and ESR1Y537S, elacestrant, a second-line ER degrader, improves progression-free survival. Therefore, given the lack of response to multimodality therapies, elacestrant was initiated in this patient after the third cycle of radiotherapy. Elacestrant, along with radiotherapy, controlled tumor growth and significantly reduced prolactin levels.</p><p><strong>Conclusion: </strong>Molecular profiling allowed the identification of ESR1Y537S, in an aggressive prolactinoma. ESR1Y537S was not detected early in the course of the disease and is likely conferring tumor aggressiveness. This finding emphasizes the significance of estrogen receptor signaling in prolactinomas. It also allowed the use of targeted therapy with successful control of disease progression.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Microarchitecture in Older Men with Type 2 Diabetes: The Importance of Bone Size.","authors":"Julien Paccou","doi":"10.1210/clinem/dgae614","DOIUrl":"https://doi.org/10.1210/clinem/dgae614","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of patients with familial chylomicronemia syndrome and multifactorial chylomicronemia syndrome.","authors":"Catherine M Spagnuolo, Jian Wang, Adam D McIntyre, Brooke A Kennedy, Robert A Hegele","doi":"10.1210/clinem/dgae613","DOIUrl":"https://doi.org/10.1210/clinem/dgae613","url":null,"abstract":"<p><strong>Context: </strong>Patients with rare familial chylomicronemia syndrome (FCS) and relatively common multifactorial chylomicronemia syndrome (MCS) both express severe hypertriglyceridemia, defined as plasma triglyceride concentration ≥10 mmol/L (≥885 mg/dL). Clinically there can be confusion between the two conditions.</p><p><strong>Objective: </strong>To compare clinical and biochemical phenotypes in patients with genotypically characterized FCS and MCS.</p><p><strong>Methods: </strong>We performed targeted sequencing of DNA from 193 patients with severe hypertriglyceridemia, classified them as having either FCS or MCS and compared clinical and biochemical characteristics.</p><p><strong>Results: </strong>FCS compared to MCS patients were significantly younger (31.4 ± 16.7 vs. 51.0 ± 11.3 years; P =0.003), with earlier age at symptom onset (15.0 ± 15.8 vs. 37.8 ± 8.8 years; P =0.00066), lower body mass index (23.3 ± 3.1 vs. 30.7 ± 5.0 kg/m2; P =0.000016), and higher prevalence of pancreatitis events (81.8% vs. 35.2%; P=0.003). Furthermore, FCS compared to MCS patients had a higher ratio of triglyceride to total cholesterol, i.e. 4.18 ± 0.92 vs 1.08 ± 0.51 (P <0.0001) and lower plasma apolipoprotein B, i.e. 0.56 ± 0.15 vs 1.02 ± 0.43 g/L (P <0.0001). MCS patients with heterozygous pathogenic variants had a relatively more severe clinical presentation than other MCS genetic subgroups.</p><p><strong>Conclusions: </strong>FCS patients have notable phenotypic differences from MCS patients, although there is overlap. While genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.2% of MCS patients with sustained refractory hypertriglyceridemia behave functionally as if they have FCS, which should influence their eligibility for novel therapies for severe hypertriglyceridemia.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Pregnancy Plasma Per- and Polyfluoroalkyl Substances (PFAS) and Maternal Midlife Adiposity.","authors":"Jordan A Burdeau, Briana J K Stephenson, Jorge E Chavarro, Shruthi Mahalingaiah, Emma V Preston, Marie-France Hivert, Emily Oken, Antonia M Calafat, Sheryl L Rifas-Shiman, Ami R Zota, Tamarra James-Todd","doi":"10.1210/clinem/dgae542","DOIUrl":"https://doi.org/10.1210/clinem/dgae542","url":null,"abstract":"<p><strong>Context: </strong>Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity.</p><p><strong>Objective: </strong>Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife.</p><p><strong>Methods: </strong>We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR).</p><p><strong>Results: </strong>Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture.</p><p><strong>Conclusion: </strong>Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum steroid profiling in the diagnosis of adrenocortical carcinoma: a prospective cohort study.","authors":"Kai Yu, Shobana Athimulam, Jasmine Saini, Ravinder Jeet Kaur, Qingping Xue, Travis J McKenzie, Ravinder J Singh, Stefan Grebe, Irina Bancos","doi":"10.1210/clinem/dgae604","DOIUrl":"https://doi.org/10.1210/clinem/dgae604","url":null,"abstract":"<p><strong>Context: </strong>Guidelines suggest performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of adrenocortical carcinoma (ACC). However, urine steroid profiling is not widely available.</p><p><strong>Objective: </strong>To determine the accuracy of clinically available serum 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC.</p><p><strong>Methods: </strong>We conducted a prospective single-center cohort study of patients with adrenal masses evaluated between 2015-2023. Serum was analyzed by liquid chromatography-mass spectrometry for 17OH-pregnenolone, 17OH-progesterone, 11-deoxycortisol. Reference standard for adrenal mass included histopathology, imaging characteristics, imaging follow up of 2 years, or clinical follow up of 5 years. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC).</p><p><strong>Results: </strong>Of 263 patients with adrenal masses, 44 (16.7%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. Hounsfield unit (HU) ≥ 20 was demonstrated in all ACCs, in all but one other adrenal malignancy, and in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs non-ACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU ≥ 20 (P<0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823.</p><p><strong>Conclusions: </strong>We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity.","authors":"Kagan E Karakus, Theodore Fleury, Erin E Baschal, Kristen A McDaniel, Hyelin Choi, Taylor K Armstrong, Liping Yu, Kimber M Simmons, Aaron W Michels","doi":"10.1210/clinem/dgae608","DOIUrl":"https://doi.org/10.1210/clinem/dgae608","url":null,"abstract":"<p><strong>Context: </strong>Type 1 diabetes incidence continues to increase in children, especially among Hispanic Whites (HW).</p><p><strong>Objective: </strong>We investigated the clinical, immunologic, and genetic characteristics of HW and Non-Hispanic White (NHW) children that presented at type 1 diabetes diagnosis.</p><p><strong>Methods: </strong>In this single-center, observational study, children who were diagnosed with type 1 diabetes (<20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included in the study and divided into two groups by Hispanic ethnicity.</p><p><strong>Results: </strong>Of 1297 children, 398 HW children presented with a younger age at diabetes onset (10.2 ± 3.9 vs. 11.1 ± 4.1 years, p<0.001) and more diabetic ketoacidosis (62.4% vs. 51.9%, p<0.001) compared to NHW children (n=899). There was no difference in sex, A1c levels, or the number and prevalence of islet autoantibodies between the two cohorts. A subset of our cohort was HLA typed as specific alleles confer strong genetic risk for type 1 diabetes (e.g., HLA-DR4 and DQ8). Among 637 HLA-typed children, HW children had a significantly higher prevalence of the DR4-DQ8 haplotype compared to NHW children (79.1% vs. 60.1%, p<0.001), and this frequency was much higher than a reference Hispanic population (OR = 6.5, 95% CI 4.6-9.3).</p><p><strong>Conclusions: </strong>Hispanic White children developing type 1 diabetes have a high prevalence of HLA DR4-DQ8, which can be utilized to select individuals for immune monitoring with islet autoantibodies to lessen diabetic ketoacidosis and potentially prevent diabetes onset.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of atrial fibrillation screening according to thyroid function: Post-hoc analysis of the randomized LOOP study.","authors":"Daniel Camillo Spona, Diana My Frodi, Lucas Yixi Xing, Emilie Katrine Kongebro, Ketil Jørgen Haugan, Claus Graff, Søren Højberg, Derk Krieger, Axel Brandes, Lars Køber, Morten S Olesen, Andreas Andersen, Sofie Hædersdal, Ruth Frikke-Schmidt, Jesper Hastrup Svendsen, Søren Zöga Diederichsen","doi":"10.1210/clinem/dgae610","DOIUrl":"https://doi.org/10.1210/clinem/dgae610","url":null,"abstract":"<p><strong>Purpose: </strong>Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk. This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels.</p><p><strong>Methods: </strong>An AF screening trial (the LOOP study) was analyzed post-hoc according to baseline TSH. The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included major bleeding, all-cause death, and the combination of stroke, SE, and cardiovascular death.</p><p><strong>Results: </strong>TSH measurement was available in 6003 of 6004 trial participants, 1500 randomized to implantable loop recorder (ILR) screening for AF and anticoagulation upon detection vs. 4503 to usual care; mean age was 74.7±4.1 years and 2836 (47%) were women. AF detection was approximately triple for ILR vs usual care across TSH tertiles (adjusted p-interaction=0.44). In the first tertile, screening was associated with decreased risk of the primary outcome (hazard ratio 0.52 [0.30-0.90]; p=0.02) and stroke, SE, or cardiovascular death (hazard ratio 0.54 [0.34-0.84]; p=0.006) compared to usual care, while no effect was observed among participants with higher TSH (adjusted p-interaction 0.03 and 0.01, respectively). There was no effect on other outcomes. Analyses of continuous TSH or excluding those with abnormal TSH or thyroid medication showed similar results.</p><p><strong>Conclusion: </strong>AF screening and subsequent treatment was associated with decreased stroke risk among participants with low TSH, though the yield of screening was similar across TSH levels. TSH may be useful as a marker to indicate benefit from AF screening vs. overdiagnosis and overtreatment. These findings should be considered exploratory and warrant further study.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, identifier: NCT0203645.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presentation, Management, and Outcomes of Patients with Giant Pheochromocytoma: Retrospective Cohort Study.","authors":"Bahar Bahrani Fard, Nasrin Nikravangolsefid, Justin W Maroun, Ashton Cross, Trenton Foster, Travis J McKenzie, Benzon Dy, Melanie Lyden, William F Young, Irina Bancos","doi":"10.1210/clinem/dgae612","DOIUrl":"https://doi.org/10.1210/clinem/dgae612","url":null,"abstract":"<p><strong>Context: </strong>Data on giant pheochromocytomas (PHEO), defined based on size ≥ 10 cm, are scarce.</p><p><strong>Objective: </strong>to compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs.</p><p><strong>Design: </strong>retrospective cohort study, 2000-2023.</p><p><strong>Setting: </strong>referral center.</p><p><strong>Patients: </strong>consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at a 1:6 ratio.</p><p><strong>Outcomes: </strong>perioperative complications, metastases, mortality.</p><p><strong>Results: </strong>Of 828 patients with PHEO, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%, P<.0001).Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% referents. In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a higher perioperative complication rate (31% vs 10%, P=.004).During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P=.02).</p><p><strong>Conclusion: </strong>Patients with giant PHEO as compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}