Dongyun Zhang, Willy Hugo, Marvin Bergsneider, Marilene B Wang, Won Kim, Karam Han, Harry V Vinters, Anthony P Heaney
Objective: Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells.
Design and methods: Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.
Results: Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples.
Conclusions: Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.
目的:揭示多巴胺激动剂疗法在人类催乳素瘤及其邻近基质和免疫细胞中的靶上和靶下作用的潜在机制:揭示多巴胺受体激动剂治疗在人类泌乳素瘤肿瘤及邻近基质细胞和免疫细胞中的靶上和靶下作用的潜在机制:通过单细胞RNA测序(scRNA-seq)分析了3名接受过卡贝戈林(CBG)治疗的患者和2名未接受过治疗的患者的5个手术切除的泌乳素瘤,以比较细胞组成和转录情况:观察到六种主要细胞群,包括肿瘤细胞(88.2%)、免疫细胞(5.6%)、基质细胞(4.9%)、祖细胞(0.6%)、增殖细胞(0.4%)和红细胞(0.2%)。经 CBG 治疗的患者的肿瘤细胞表达了较低水平的激素分泌调控基因,如 SCG2、VGF、TIMP1、NNAT 和 CALD1,这与 CBG 对激素加工和分泌的抑制作用是一致的。有趣的是,我们还在 CBG 处理过的组织中观察到 CD8+ T 细胞数量的增加。这些细胞毒性 CD8+ T 细胞表达杀伤性颗粒成分,如穿孔素、颗粒酶 GZMB、GNLY 和 KLRD1 以及炎性细胞因子 CCL5。研究人员进一步分析了这些 CD8+ T 细胞的免疫细胞活化情况,发现 CBG 处理样本的 CD8+ T 细胞中 CD25(IL2R)表达增加。此外,我们还注意到,CBG 处理的样本中基质细胞数量较多,这也证实了之前的报道:我们的 scRNAseq 研究揭示了 CBG 处理过的 PRLomas 与未处理过的 PRLomas 在肿瘤和微环境细胞成分方面的转录组特征的关键差异,并首次描述了之前未知的 CD8+ T 细胞在 CBG 处理后的活化,这可能在 CBG 的杀瘤作用中发挥作用。
{"title":"Cabergoline targets multiple pathways to inhibit PRL secretion and increases stromal fibrosis.","authors":"Dongyun Zhang, Willy Hugo, Marvin Bergsneider, Marilene B Wang, Won Kim, Karam Han, Harry V Vinters, Anthony P Heaney","doi":"10.1093/ejendo/lvae055","DOIUrl":"10.1093/ejendo/lvae055","url":null,"abstract":"<p><strong>Objective: </strong>Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells.</p><p><strong>Design and methods: </strong>Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.</p><p><strong>Results: </strong>Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples.</p><p><strong>Conclusions: </strong>Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A van der Velden, Philippe F Backeljauw
Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.
{"title":"Clinical practice guidelines for the care of girls and women with Turner syndrome.","authors":"Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A van der Velden, Philippe F Backeljauw","doi":"10.1093/ejendo/lvae050","DOIUrl":"10.1093/ejendo/lvae050","url":null,"abstract":"<p><p>Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linda Kujanpää, Riikka K Arffman, Paula Pesonen, Elisa Hurskainen, Marjo-Riitta Järvelin, Stephen Franks, Juha S Tapanainen, Laure Morin-Papunen, Terhi T Piltonen
Objective: This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort.
Patients: Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1556) in the Northern Finland Birth Cohort 1966.
Main outcome measures: National register data on diagnosed diseases (International Statistical Classification of Diseases [ICD]-8-10) and medication use (Anatomical Therapeutic Chemical) until the age of 50.
Results: Women with PCOS had a 26% higher risk for any registered diagnosis (risk ratio [RR]: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared with non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, eg, endocrine, metabolic, nervous system, musculoskeletal, and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a body mass index (BMI) ≥ 25 kg/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI < 25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, eg, medications related to the alimentary tract and metabolism, the cardiovascular system, genitourinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems.
Conclusion: Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.
{"title":"Polycystic ovary syndrome presents as a multimorbid condition by age 50: birth cohort linkage to national register data.","authors":"Linda Kujanpää, Riikka K Arffman, Paula Pesonen, Elisa Hurskainen, Marjo-Riitta Järvelin, Stephen Franks, Juha S Tapanainen, Laure Morin-Papunen, Terhi T Piltonen","doi":"10.1093/ejendo/lvae057","DOIUrl":"10.1093/ejendo/lvae057","url":null,"abstract":"<p><strong>Objective: </strong>This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort.</p><p><strong>Design: </strong>Population-based longitudinal cohort study.</p><p><strong>Patients: </strong>Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1556) in the Northern Finland Birth Cohort 1966.</p><p><strong>Main outcome measures: </strong>National register data on diagnosed diseases (International Statistical Classification of Diseases [ICD]-8-10) and medication use (Anatomical Therapeutic Chemical) until the age of 50.</p><p><strong>Results: </strong>Women with PCOS had a 26% higher risk for any registered diagnosis (risk ratio [RR]: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared with non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, eg, endocrine, metabolic, nervous system, musculoskeletal, and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a body mass index (BMI) ≥ 25 kg/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI < 25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, eg, medications related to the alimentary tract and metabolism, the cardiovascular system, genitourinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems.</p><p><strong>Conclusion: </strong>Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Sampedro-Nuñez, Aura Dulcinea Herrera-Martínez, Alejandro Ibáñez-Costa, Esther Rivero-Cortés, Eva Venegas, Mercedes Robledo, Rebeca Martínez-Hernández, Araceli García-Martínez, Joan Gil, Mireia Jordà, Judith López-Fernández, Inmaculada Gavilán, Silvia Maraver, Montserrat Marqués-Pamies, Rosa Cámara, Carmen Fajardo-Montañana, Elena Valassi, Elena Dios, Anna Aulinas, Betina Biagetti, Cristina Álvarez Escola, Marta Araujo-Castro, Concepción Blanco, de Miguel Paz, Rocío Villar-Taibo, Clara V Álvarez, Sonia Gaztambide, Susan M Webb, Luis Castaño, Ignacio Bernabéu, Antonio Picó, María-Ángeles Gálvez, Alfonso Soto-Moreno, Manel Puig-Domingo, Justo P Castaño, Mónica Marazuela, Raúl M Luque
Introduction: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management.
Objectives: The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression.
Methods: Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables.
Results: Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs).
Conclusions: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.
{"title":"Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study.","authors":"Miguel Sampedro-Nuñez, Aura Dulcinea Herrera-Martínez, Alejandro Ibáñez-Costa, Esther Rivero-Cortés, Eva Venegas, Mercedes Robledo, Rebeca Martínez-Hernández, Araceli García-Martínez, Joan Gil, Mireia Jordà, Judith López-Fernández, Inmaculada Gavilán, Silvia Maraver, Montserrat Marqués-Pamies, Rosa Cámara, Carmen Fajardo-Montañana, Elena Valassi, Elena Dios, Anna Aulinas, Betina Biagetti, Cristina Álvarez Escola, Marta Araujo-Castro, Concepción Blanco, de Miguel Paz, Rocío Villar-Taibo, Clara V Álvarez, Sonia Gaztambide, Susan M Webb, Luis Castaño, Ignacio Bernabéu, Antonio Picó, María-Ángeles Gálvez, Alfonso Soto-Moreno, Manel Puig-Domingo, Justo P Castaño, Mónica Marazuela, Raúl M Luque","doi":"10.1093/ejendo/lvae045","DOIUrl":"10.1093/ejendo/lvae045","url":null,"abstract":"<p><strong>Introduction: </strong>Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management.</p><p><strong>Objectives: </strong>The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression.</p><p><strong>Methods: </strong>Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables.</p><p><strong>Results: </strong>Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs).</p><p><strong>Conclusions: </strong>A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Betina Biagetti, Marta Araujo-Castro, Edelmiro Menéndez Torre, Iría Novoa-Testa, Fernando Cordido, Eider Pascual Corrales, Víctor Rodríguez Berrocal, Fernando Guerrero-Pérez, Almudena Vicente, Juan Carlos Percovich, Rogelio García Centeno, Laura González, María Dolores Ollero García, Ana Irigaray Echarri, María Dolores Moure Rodríguez, Cristina Novo-Rodríguez, María Calatayud, Rocío Villar-Taibo, Ignacio Bernabéu, Cristina Alvarez-Escola, Pamela Benítez Valderrama, Carmen Tenorio-Jiménez, Pablo Abellán Galiana, Eva Venegas Moreno, Inmaculada González Molero, Pedro Iglesias, Concepción Blanco, Fernando Vidal-Ostos De Lara, Paz de Miguel, Elena López Mezquita, Felicia Hanzu, Iban Aldecoa, Silvia Aznar, Cristina Lamas, Anna Aulinas, Queralt Asla Roca, Paola Gracia, José María Recio Córdova, Mariola Aviles, Diego Asensio-Wandosel, Miguel Sampedro, Rosa Cámara, Miguel Paja, Ignacio Ruz-Caracuel, Carmen Fajardo-Montañana, Esteban Cordero Asanza, Elena Martinez-Saez, Mónica Marazuela, Manel Puig-Domingo
Objective: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA).
Design: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment.
Methods: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality.
Results: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline.
Conclusion: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.
{"title":"Effectiveness of combined first-line medical treatment in acromegaly with prolactin cosecretion.","authors":"Betina Biagetti, Marta Araujo-Castro, Edelmiro Menéndez Torre, Iría Novoa-Testa, Fernando Cordido, Eider Pascual Corrales, Víctor Rodríguez Berrocal, Fernando Guerrero-Pérez, Almudena Vicente, Juan Carlos Percovich, Rogelio García Centeno, Laura González, María Dolores Ollero García, Ana Irigaray Echarri, María Dolores Moure Rodríguez, Cristina Novo-Rodríguez, María Calatayud, Rocío Villar-Taibo, Ignacio Bernabéu, Cristina Alvarez-Escola, Pamela Benítez Valderrama, Carmen Tenorio-Jiménez, Pablo Abellán Galiana, Eva Venegas Moreno, Inmaculada González Molero, Pedro Iglesias, Concepción Blanco, Fernando Vidal-Ostos De Lara, Paz de Miguel, Elena López Mezquita, Felicia Hanzu, Iban Aldecoa, Silvia Aznar, Cristina Lamas, Anna Aulinas, Queralt Asla Roca, Paola Gracia, José María Recio Córdova, Mariola Aviles, Diego Asensio-Wandosel, Miguel Sampedro, Rosa Cámara, Miguel Paja, Ignacio Ruz-Caracuel, Carmen Fajardo-Montañana, Esteban Cordero Asanza, Elena Martinez-Saez, Mónica Marazuela, Manel Puig-Domingo","doi":"10.1093/ejendo/lvae053","DOIUrl":"10.1093/ejendo/lvae053","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA).</p><p><strong>Design: </strong>This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment.</p><p><strong>Methods: </strong>Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality.</p><p><strong>Results: </strong>Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline.</p><p><strong>Conclusion: </strong>In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to letter from Dr. Al-Salameh.","authors":"Suranut Charoensri, Richard J Auchus","doi":"10.1093/ejendo/lvae058","DOIUrl":"10.1093/ejendo/lvae058","url":null,"abstract":"","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iben Rix, Asger B Lund, Lars F Garvey, Carsten P Hansen, Elizaveta Chabanova, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Gerrit Van Hall, Filip K Knop
Objective: The metabolic phenotype of totally pancreatectomised patients includes hyperaminoacidaemia and predisposition to hypoglycaemia and hepatic lipid accumulation. We aimed to investigate whether the loss of pancreatic glucagon may be responsible for these changes.
Methods: Nine middle-aged, normal-weight totally pancreatectomised patients, nine patients with type 1 diabetes (C-peptide negative), and nine matched controls underwent two separate experimental days, each involving a 150-min intravenous infusion of glucagon (4 ng/kg/min) or placebo (saline) under fasting conditions while any basal insulin treatment was continued.
Results: Glucagon infusion increased plasma glucagon to similar high physiological levels in all groups. The infusion increased hepatic glucose production and decreased plasma concentration of most amino acids in all groups, with more pronounced effects in the totally pancreatectomised patients compared with the other groups. Glucagon infusion diminished fatty acid re-esterification and tended to decrease plasma concentrations of fatty acids in the totally pancreatectomised patients but not in the type 1 diabetes patients.
Conclusion: Totally pancreatectomised patients were characterised by increased sensitivity to exogenous glucagon at the level of hepatic glucose, amino acid, and lipid metabolism, suggesting that the metabolic disturbances characterising these patients may be rooted in perturbed hepatic processes normally controlled by pancreatic glucagon.
{"title":"Increased hepatic glucagon sensitivity in totally pancreatectomised patients.","authors":"Iben Rix, Asger B Lund, Lars F Garvey, Carsten P Hansen, Elizaveta Chabanova, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Gerrit Van Hall, Filip K Knop","doi":"10.1093/ejendo/lvae054","DOIUrl":"10.1093/ejendo/lvae054","url":null,"abstract":"<p><strong>Objective: </strong>The metabolic phenotype of totally pancreatectomised patients includes hyperaminoacidaemia and predisposition to hypoglycaemia and hepatic lipid accumulation. We aimed to investigate whether the loss of pancreatic glucagon may be responsible for these changes.</p><p><strong>Methods: </strong>Nine middle-aged, normal-weight totally pancreatectomised patients, nine patients with type 1 diabetes (C-peptide negative), and nine matched controls underwent two separate experimental days, each involving a 150-min intravenous infusion of glucagon (4 ng/kg/min) or placebo (saline) under fasting conditions while any basal insulin treatment was continued.</p><p><strong>Results: </strong>Glucagon infusion increased plasma glucagon to similar high physiological levels in all groups. The infusion increased hepatic glucose production and decreased plasma concentration of most amino acids in all groups, with more pronounced effects in the totally pancreatectomised patients compared with the other groups. Glucagon infusion diminished fatty acid re-esterification and tended to decrease plasma concentrations of fatty acids in the totally pancreatectomised patients but not in the type 1 diabetes patients.</p><p><strong>Conclusion: </strong>Totally pancreatectomised patients were characterised by increased sensitivity to exogenous glucagon at the level of hepatic glucose, amino acid, and lipid metabolism, suggesting that the metabolic disturbances characterising these patients may be rooted in perturbed hepatic processes normally controlled by pancreatic glucagon.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cihan Atila, Julia Beck, Julie Refardt, Zoran Erlic, Juliana B Drummond, Clara O Sailer, Matthias E Liechti, Beatriz Santana Soares Rocha, Felix Beuschlein, Bettina Winzeler, Mirjam Christ-Crain
Objective: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist.
Design: Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)].
Methods: Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health.
Results: Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01).
Conclusion: This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.
{"title":"Psychopathological characteristics in patients with arginine vasopressin deficiency (central diabetes insipidus) and primary polydipsia compared to healthy controls.","authors":"Cihan Atila, Julia Beck, Julie Refardt, Zoran Erlic, Juliana B Drummond, Clara O Sailer, Matthias E Liechti, Beatriz Santana Soares Rocha, Felix Beuschlein, Bettina Winzeler, Mirjam Christ-Crain","doi":"10.1093/ejendo/lvae040","DOIUrl":"10.1093/ejendo/lvae040","url":null,"abstract":"<p><strong>Objective: </strong>Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist.</p><p><strong>Design: </strong>Data from two studies involving 82 participants [39 AVP-D, 28 PP, and 15 healthy controls (HC)].</p><p><strong>Methods: </strong>Psychological evaluations were conducted using standardized questionnaires measuring anxiety [State-Trait Anxiety Inventory (STAI)], alexithymia [Toronto Alexithymia Scale (TAS-20)], depressive symptoms (Beck's Depression Inventory-II (BDI-II), and overall mental health [Short Form-36 Health Survey (SF-36)]. Higher STAI, TAS-20, and BDI-II scores suggest elevated anxiety, alexithymia, and depression, while higher SF-36 scores signify better overall mental health.</p><p><strong>Results: </strong>Compared to HC, patients with AVP-D and PP showed higher levels of anxiety (HC 28 points [24-31] vs AVP-D 36 points [31-45]; vs PP 38 points [33-46], P < .01), alexithymia (HC 30 points [29-37] vs AVP-D 43 points [35-54]; vs PP 46 points [37-55], P < .01), and depression (HC 1 point [0-2] vs AVP-D 7 points [4-14]; vs PP 7 points [3-13], P < .01). Levels of anxiety, alexithymia, and depression showed no difference between both patient groups (P = .58, P = .90, P = .50, respectively). Compared to HC, patients with AVP-D and PP reported similarly reduced self-reported overall mental health scores (HC 84 [68-88] vs AVP-D 60 [52-80], P = .05; vs PP 60 [47-74], P < .01).</p><p><strong>Conclusion: </strong>This study reveals heightened anxiety, alexithymia, depression, and diminished overall mental health in patients with AVP-D and PP. The results emphasize the need for careful interpretation of psychopathological characteristics to differentiate between AVP-D and PP.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felix Beuschlein, Tobias Else, Irina Bancos, Stefanie Hahner, Oksana Hamidi, Leonie van Hulsteijn, Eystein S Husebye, Niki Karavitaki, Alessandro Prete, Anand Vaidya, Christine Yedinak, Olaf M Dekkers
Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.
{"title":"European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency.","authors":"Felix Beuschlein, Tobias Else, Irina Bancos, Stefanie Hahner, Oksana Hamidi, Leonie van Hulsteijn, Eystein S Husebye, Niki Karavitaki, Alessandro Prete, Anand Vaidya, Christine Yedinak, Olaf M Dekkers","doi":"10.1093/ejendo/lvae029","DOIUrl":"10.1093/ejendo/lvae029","url":null,"abstract":"<p><p>Glucocorticoids are widely prescribed as anti-inflammatory and immunosuppressive agents. This results in at least 1% of the population using chronic glucocorticoid therapy, being at risk for glucocorticoid-induced adrenal insufficiency. This risk is dependent on the dose, duration and potency of the glucocorticoid, route of administration, and individual susceptibility. Once glucocorticoid-induced adrenal insufficiency develops or is suspected, it necessitates careful education and management of affected patients. Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency. In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing. The degree and persistence of HPA axis suppression after cessation of glucocorticoid therapy are dependent on overall exposure and recovery of adrenal function varies greatly amongst individuals. This first European Society of Endocrinology/Endocrine Society joint clinical practice guideline provides guidance on this clinically relevant condition to aid clinicians involved in the care of patients on chronic glucocorticoid therapy.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coco M Fuhri Snethlage, Abraham S Meijnikman, Anne Linde Mak, Elena Rampanelli, Bas Voermans, Cengiz A K Callender, Pleun de Groen, Bart O Roep, Daniël H van Raalte, Filip K Knop, Adriaan G Holleboom, Max Nieuwdorp, Nordin M J Hanssen
Aims/hypothesis: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.
Methods: A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis.
Results: The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03.
Conclusion: Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.
目的/假设:1型糖尿病中MASLD的患病率和严重程度仍不清楚。因此,我们调查了 MASLD 在 1 型糖尿病中的患病率和严重程度,并评估了哪些临床特征对预测 MASLD 的严重程度最为重要。4±4.2kg/m2,HbA1c 55.6±12mmol/mol)进行了振动控制瞬态弹性成像(VCTE),用受控衰减参数(CAP)评分(≥280.0dB/m)表示脂肪变性,用肝硬度测量(LMS)表示肝纤维化(≥8.0kPa)。通过机器学习 Extra-Trees 分类模型评估了 1 型糖尿病相关临床特征对脂肪变性和肝纤维化的预测能力:结果:肝脏脂肪变性和肝纤维化的发生率分别为 9.5% [95% CI 6.8-12.2] 和 3.5% [95% CI 1.8-5.2]。LMS 较高与 1 型糖尿病病程较长(中位数 30.5 [IQR 18.0-39.3] 年 vs. 15.0 [IQR 6.0-27.0] 年)、年龄较大、体重指数较高(平均值 27.8 ±5.2 vs. 25.3 ±4.1kg/m2)和 CAP 评分较高(平均值 211.4±51.7 dB/m vs. 241.4±75.6 dB/m)有关。最重要的纤维化预测特征是 1 型糖尿病持续时间、年龄和收缩压,其平均值(± 标准差)曲线下面积为 0.73±0.03:结论:患有 1 型糖尿病和高血压、年龄较大、体重指数和病程长的人可被视为罹患 MASLD 的高危人群。
{"title":"Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.","authors":"Coco M Fuhri Snethlage, Abraham S Meijnikman, Anne Linde Mak, Elena Rampanelli, Bas Voermans, Cengiz A K Callender, Pleun de Groen, Bart O Roep, Daniël H van Raalte, Filip K Knop, Adriaan G Holleboom, Max Nieuwdorp, Nordin M J Hanssen","doi":"10.1093/ejendo/lvae043","DOIUrl":"10.1093/ejendo/lvae043","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.</p><p><strong>Methods: </strong>A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis.</p><p><strong>Results: </strong>The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03.</p><p><strong>Conclusion: </strong>Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}