Luca Boeri, Edoardo Pozzi, Federico Belladelli, Christian Corsini, Simone Cilio, Alessandro Bertini, Francesco Lanzaro, Luigi Candela, Massimiliano Raffo, Fausto Negri, Ludovica Cella, Margherita Fantin, Giuseppe Fallara, Paolo Capogrosso, Alessia d'Arma, Francesco Montorsi, Andrea Salonia
Objectives
To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men.
Design, Patients, Measurements
Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort.
Results
Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values.
Conclusions
Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.
{"title":"One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice","authors":"Luca Boeri, Edoardo Pozzi, Federico Belladelli, Christian Corsini, Simone Cilio, Alessandro Bertini, Francesco Lanzaro, Luigi Candela, Massimiliano Raffo, Fausto Negri, Ludovica Cella, Margherita Fantin, Giuseppe Fallara, Paolo Capogrosso, Alessia d'Arma, Francesco Montorsi, Andrea Salonia","doi":"10.1111/cen.15093","DOIUrl":"10.1111/cen.15093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients, Measurements</h3>\u0000 \u0000 <p>Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (<i>p</i> = .02), had higher Follicle-stimulating hormone (FSH) (<i>p</i> = .04) but lower total testosterone (<i>p</i> = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (<i>p</i> = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (<i>p</i> < .001) and lower progressive sperm motility (<i>p</i> < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, <i>p</i> = .02) and higher HOMA-IR score (OR: 1.8, <i>p</i> = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141502276","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}
Mai C. Arlien-Søborg, Jakob Dal, Ansgar Heck, Kirstine Stochholm, Eigil Husted, Claus Larsen Feltoft, Åse Krogh Rasmussen, Ulla Feldt-Rasmussen, Mikkel Andreassen, Marianne Christina Klose, Torben Leo Nielsen, Marianne Skovsager Andersen, Louise Lehmann Christensen, Jesper Krogh, Anne Jarlov, Jens Bollerslev, Ingrid Nermoen, Marianne Oksnes, Per Dahlqvist, Tommy Olsson, Katarina Berinder, Charlotte Hoybye, Maria Petersson, Anna-karin Akerman, Jeanette Wahlberg, Bertil Ekman, Britt Eden Engstrom, Gudmundur Johannsson, Oskar Ragnarsson, Daniel Olsson, Helga Ágústa Sigurjónsdóttir, Stine Lyngvi Fougner, Niina Matikainen, Satu Vehkavaara, Saara Metso, Pia Jaatinen, Päivi Hämäläinen, Reeta Rintamäki, Iina Yliaska, Heidi Immonen, Sari Mäkimattila, Henna Cederberg-Tamminen, Marianna Viukari, Pasi Nevalainen, Pirjo Nuutila, Camilla Schalin-Jäntti, Pia Burman, Jens Otto Lunde Jørgensen
Objective
Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.
Methods
A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.
Results
Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.
Conclusion
This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
{"title":"Acromegaly management in the Nordic countries: A Delphi consensus survey","authors":"Mai C. Arlien-Søborg, Jakob Dal, Ansgar Heck, Kirstine Stochholm, Eigil Husted, Claus Larsen Feltoft, Åse Krogh Rasmussen, Ulla Feldt-Rasmussen, Mikkel Andreassen, Marianne Christina Klose, Torben Leo Nielsen, Marianne Skovsager Andersen, Louise Lehmann Christensen, Jesper Krogh, Anne Jarlov, Jens Bollerslev, Ingrid Nermoen, Marianne Oksnes, Per Dahlqvist, Tommy Olsson, Katarina Berinder, Charlotte Hoybye, Maria Petersson, Anna-karin Akerman, Jeanette Wahlberg, Bertil Ekman, Britt Eden Engstrom, Gudmundur Johannsson, Oskar Ragnarsson, Daniel Olsson, Helga Ágústa Sigurjónsdóttir, Stine Lyngvi Fougner, Niina Matikainen, Satu Vehkavaara, Saara Metso, Pia Jaatinen, Päivi Hämäläinen, Reeta Rintamäki, Iina Yliaska, Heidi Immonen, Sari Mäkimattila, Henna Cederberg-Tamminen, Marianna Viukari, Pasi Nevalainen, Pirjo Nuutila, Camilla Schalin-Jäntti, Pia Burman, Jens Otto Lunde Jørgensen","doi":"10.1111/cen.15095","DOIUrl":"10.1111/cen.15095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (<i>n</i> = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310211","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}
Roberto Negro, Miloš Žarković, Roberto Attanasio, Laszlo Hegedüs, Endre V. Nagy, Enrico Papini, Ersin Akarsu, Maria Alevizaki, Göksun Ayvaz, Tomasz Bednarczuk, Biljana Nedeljković Beleslin, Eszter Berta, Miklos Bodor, Anna Maria Borissova, Mihail Boyanov, Camille Buffet, Maria-Cristina Burlacu, Jamina Ćirić, Chagit Adler Cohen, Juan J. Díez, Harald Dobnig, Valentin Fadeyev, Benjamin C. T. Field, Eric Fliers, Dagmar Führer, Juan C. Galofré, Tommi Hakala, Jiskra Jan, Peter Kopp, Michael Krebs, Michal Kršek, Martin Kužma, Laurence Leenhardt, Vitaliy Luchytskiy, Francisca Marques Puga, Anne McGowan, Miguel Melo, Saara Metso, Carla Moran, Tatyana Morgunova, Dan Alexandru Niculescu, Božidar Perić, Tereza Planck, Catalina Poiana, Eyal Robenshtok, Patrick Olivier Rosselet, Marek Ruchala, Kamilla Ryom Riis, Alla Shepelkevich, Mykola Tronko, David Unuane, Irfan Vardarli, Edward Visser, Andromachi Vryonidou, Younes R. Younes, Petros Perros
Objectives
The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients.
Design
The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb.
Results
A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients (“weekly” [OR: 1.4; CI: 1.0–1.9], “daily” [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4.
Conclusions
A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.
{"title":"Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey)","authors":"Roberto Negro, Miloš Žarković, Roberto Attanasio, Laszlo Hegedüs, Endre V. Nagy, Enrico Papini, Ersin Akarsu, Maria Alevizaki, Göksun Ayvaz, Tomasz Bednarczuk, Biljana Nedeljković Beleslin, Eszter Berta, Miklos Bodor, Anna Maria Borissova, Mihail Boyanov, Camille Buffet, Maria-Cristina Burlacu, Jamina Ćirić, Chagit Adler Cohen, Juan J. Díez, Harald Dobnig, Valentin Fadeyev, Benjamin C. T. Field, Eric Fliers, Dagmar Führer, Juan C. Galofré, Tommi Hakala, Jiskra Jan, Peter Kopp, Michael Krebs, Michal Kršek, Martin Kužma, Laurence Leenhardt, Vitaliy Luchytskiy, Francisca Marques Puga, Anne McGowan, Miguel Melo, Saara Metso, Carla Moran, Tatyana Morgunova, Dan Alexandru Niculescu, Božidar Perić, Tereza Planck, Catalina Poiana, Eyal Robenshtok, Patrick Olivier Rosselet, Marek Ruchala, Kamilla Ryom Riis, Alla Shepelkevich, Mykola Tronko, David Unuane, Irfan Vardarli, Edward Visser, Andromachi Vryonidou, Younes R. Younes, Petros Perros","doi":"10.1111/cen.15099","DOIUrl":"10.1111/cen.15099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients (“weekly” [OR: 1.4; CI: 1.0–1.9], “daily” [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295668","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}
Yuki Saito, Hidenori Kage, Kenya Kobayashi, Teru Kamogashira, Osamu Fukuoka, Koji Yamamura, Satoshi Yamashita, Masahiko Tanabe, Katsutoshi Oda, Kenji Kondo
Objective
Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the BRAF V600E mutation, and its clinical implications.
Design, Patients and Mesurement
A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and χ2 tests, were employed for survival analysis and gene mutation comparisons.
Results
Among 102 ATCs, BRAF, RAS, and other driver mutations were found in 83 cases (81.2%). The prevalence of BRAF V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the BRAF, RAS, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that RAS mutations had a poorer prognosis. In the BRAF/RAS wild-type group, FGFR1 and NF1 were identified as driver mutations, with an accumulation of copy number variations and less TERT promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data.
Conclusions
Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of BRAF V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.
{"title":"Comprehensive genomic profiling from C-CAT database unveiled over 80% presence of oncogenic drivers in anaplastic thyroid carcinoma including BRAF, RAS family, NF1, and FGFR1","authors":"Yuki Saito, Hidenori Kage, Kenya Kobayashi, Teru Kamogashira, Osamu Fukuoka, Koji Yamamura, Satoshi Yamashita, Masahiko Tanabe, Katsutoshi Oda, Kenji Kondo","doi":"10.1111/cen.15098","DOIUrl":"10.1111/cen.15098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Anaplastic thyroid carcinoma (ATC) is considered a very aggressive carcinoma and has been difficult to treat with therapeutic strategies. This study examines the landscape of genomic alteration in ATC, including the <i>BRAF</i> V600E mutation, and its clinical implications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Mesurement</h3>\u0000 \u0000 <p>A retrospective observational study was conducted using collected at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, utilizing comprehensive genomic profiling data from 102 ATC cases. Additionally, AACR-GENIE data from 267 cases were analysed for validation. Statistical methods, including the conditional Kendall tau statistic and <i>χ</i><sup>2</sup> tests, were employed for survival analysis and gene mutation comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 102 ATCs, <i>BRAF</i>, <i>RAS</i>, and other driver mutations were found in 83 cases (81.2%). The prevalence of <i>BRAF</i> V600E mutations was as high as 60%. Co-mutation analysis identified different genomic profiles in the <i>BRAF, RAS</i>, and wild-type groups. Despite the diverse molecular backgrounds, no significant differences in clinical variables and overall survival were observed. The analysis considering left-side amputation suggested that <i>RAS</i> mutations had a poorer prognosis. In the <i>BRAF/RAS</i> wild-type group, <i>FGFR1</i> and <i>NF1</i> were identified as driver mutations, with an accumulation of copy number variations and less <i>TERT</i> promoter mutations. This molecular subgrouping was also supported by the AACR-GENIE data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Comprehensive genomic analysis of ATC in Japan revealed distinct molecular subgroups, highlighting the importance of <i>BRAF</i> V600E mutations, particularly V600E, as potential therapeutic targets and suggest the relevance of tailor-made therapeutic strategies based on genomic profiling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295667","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}
Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM).
Design, Patients and Measurements
This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia.
Results
The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (p = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (r = −.117, r = −.131, r = .117, p < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, p < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76–7.52, p = .001).
Conclusion
Albuminuria is more frequently observed in patients with hypomagnesemia.
目的：糖尿病肾病是全球慢性肾病的一个普遍病因。镁在胰岛素抵抗中起着关键作用，而胰岛素反过来又调节镁的水平。我们旨在研究 2 型糖尿病（T2DM）患者低镁血症与白蛋白尿之间的关系：这项回顾性单中心研究涵盖了2019年1月至2020年8月期间在我院门诊就诊的1178名18岁及以上的T2DM患者。白蛋白尿水平根据肾脏疾病结果质量倡议指南进行分类。在文献中，当研究低镁血症的临界值时，发现研究通常使用医院的正常水平作为参考点。低镁血症的定义是镁水平低于 1.6 毫克/分升，并与正常镁血症（镁水平在 1.6 至 2.4 毫克/分升之间）进行了比较。首要目标是探讨镁水平对白蛋白尿的影响，次要目标是确定低镁血症的患病率。根据年龄、性别（男性）、HbA1c和是否存在低镁血症进行了多变量逻辑回归分析：参与者的平均年龄为 58.7 ± 12.2 岁，男性占 44%。5.3%的患者存在低镁血症。高龄和女性在低镁血症患者中更为常见（p = .001）。镁水平与 HbA1c 和空腹血糖呈负相关，与肌酐水平呈正相关（r = -.117, r = -.131, r = .117, p 结论：低镁血症患者更易出现白蛋白尿。
{"title":"The relationship between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus","authors":"Edibe S. Eker, Hayriye E. Ataoğlu","doi":"10.1111/cen.15094","DOIUrl":"10.1111/cen.15094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Diabetic nephropathy is a prevalent cause of chronic kidney disease worldwide. Magnesium plays a critical role in insulin resistance, and insulin, in turn, regulates magnesium levels. We aimed to investigate the association between hypomagnesemia and albuminuria in patients with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Measurements</h3>\u0000 \u0000 <p>This retrospective single-centre study encompassed 1178 patients aged 18 and above with T2DM, who attended our outpatient clinic between January 2019 and August 2020. Albuminuria levels were categorised according to Kidney Disease Outcomes Quality Initiative guidelines. In the literature, when examining cut-off values for hypomagnesemia, it is observed that studies typically use hospital normal level as a reference point. Hypomagnesemia, defined as magnesium levels below 1.6 mg/dL, was compared to normomagnesemia (magnesium between 1.6 and 2.4 mg/dL). The primary objective was to explore the impact of magnesium levels on albuminuria, while the secondary objective was to determine the prevalence of hypomagnesemia. The multivariate logistic regression analyses were performed according to age, gender (male), HbA1c, and presence of hypomagnesemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of the participants was 58.7 ± 12.2 years, with 44% being male. Hypomagnesemia was identified in 5.3% of the patients. Advanced age and female gender were more common among patients with hypomagnesemia (<i>p</i> = .001). Magnesium levels exhibited a negative correlation with HbA1c and fasting blood glucose, and a positive correlation with creatinine levels (<i>r</i> = −.117, <i>r</i> = −.131, <i>r</i> = .117, <i>p</i> < .001 for all three variables). Hypomagnesemia was significantly more prevalent in patients with albuminuria (15.9% vs. 4.7%, <i>p</i> < .001). Moreover, participants with the presence of hypomagnesemia were independently associated with a higher risk of albuminuria (odds ratio 3,64 1.76–7.52, <i>p</i> = .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Albuminuria is more frequently observed in patients with hypomagnesemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260910","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}
Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission.
Design, Patients and Measurements
We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission.
Results
The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff.
Conclusions
Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.
{"title":"Early identification of postoperative remission for thyrotropin-secreting adenomas","authors":"Linling Fan, Zhihong Wang, Wanwan Sun, Qiaoli Cui, Wei Wu, Boni Xiang, Zengyi Ma, Yue Wu, Yongfei Wang, Zhaoyun Zhang, Yiming Li, Min He, Hongying Ye","doi":"10.1111/cen.15066","DOIUrl":"10.1111/cen.15066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Measurements</h3>\u0000 \u0000 <p>We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179226","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}
Leontine E. H. Bakker, Marco J. T. Verstegen, Diandra C. Manole, Huangling Lu, Thomas J. M. Decramer, Iris C. M. Pelsma, Mark C. Kruit, Berit M. Verbist, Annenienke van de Ven, Mark Gurnell, Idris Ghariq, Wouter R. van Furth, Nienke R. Biermasz, Lenka M. Pereira Arias-Bouda
Objective
To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRICR) in the care trajectory for persistent acromegaly.
Design
Prospective case series.
Patients
Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.
Measurements
FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.
Results
FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRICR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.
Conclusions
In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRICR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.
{"title":"18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly","authors":"Leontine E. H. Bakker, Marco J. T. Verstegen, Diandra C. Manole, Huangling Lu, Thomas J. M. Decramer, Iris C. M. Pelsma, Mark C. Kruit, Berit M. Verbist, Annenienke van de Ven, Mark Gurnell, Idris Ghariq, Wouter R. van Furth, Nienke R. Biermasz, Lenka M. Pereira Arias-Bouda","doi":"10.1111/cen.15079","DOIUrl":"10.1111/cen.15079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To report our experience with <sup>18</sup>F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI<sup>CR</sup>) in the care trajectory for persistent acromegaly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>Prospective case series.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients</h3>\u0000 \u0000 <p>Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Measurements</h3>\u0000 \u0000 <p>FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FET-PET/MRI<sup>CR</sup> showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRI<sup>CR</sup> was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRI<sup>CR</sup> identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRI<sup>CR</sup> findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRI<sup>CR</sup> is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179225","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}
Elizabeth Burt, Melanie C. Davies, Ephia Yasmin, Antoinette Cameron-Pimblett, Vikram Talaulikar, Clementina La Rosa, Sophie A. Clarke, Gerard S. Conway
Objective
Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators.
Design
A retrospective single-centre cross-sectional study.
Patients and Measurements
Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS.
Results
In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6−10.8, p = .003) and SGA (OR: 2.92, 95% CI: 1.02−8.38, p = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34−0.84, p = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, p = .04).
Conclusions
We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.
{"title":"Fertility and pregnancy outcomes in women with Turner syndrome: A single centre experience","authors":"Elizabeth Burt, Melanie C. Davies, Ephia Yasmin, Antoinette Cameron-Pimblett, Vikram Talaulikar, Clementina La Rosa, Sophie A. Clarke, Gerard S. Conway","doi":"10.1111/cen.15078","DOIUrl":"10.1111/cen.15078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Many women with Turner syndrome (TS) will consider fertility options and pregnancy. We wished to examine the fertility and pregnancy outcomes in women with TS undergoing oocyte donation (OD) treatment or spontaneous pregnancy in a large single-centre cohort. General population reference data or data from those with idiopathic premature ovarian insufficiency were used as comparators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design</h3>\u0000 \u0000 <p>A retrospective single-centre cross-sectional study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Measurements</h3>\u0000 \u0000 <p>Seventy-four women with TS underwent OD treatment with a total of 105 pregnancies, and 31 women with TS had 71 spontaneous conceptions. Fertility outcomes included clinical pregnancy and live birth rate. Pregnancy outcomes included miscarriage rate, prevalence of hypertension, gestational diabetes, lower segment caesarean section (LSCS), small for gestational age (SGA), prematurity and vertical transmission of TS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In those with TS, OD pregnancies were associated with increased rates of LSCS and SGA compared to spontaneous pregnancies; LSCS (OR: 4.19, 95% CI: 1.6−10.8, <i>p</i> = .003) and SGA (OR: 2.92, 95% CI: 1.02−8.38, <i>p</i> = .04). There were no recorded cardiac events but 5 (17.2%) cases of vertical transmissions of TS in daughters were identified. OD in those with TS was associated with a lower live birth rate per cycle started (OR: 0.53, 95% CI: 0.34−0.84, <i>p</i> = .008) and a higher rate of miscarriage compared to women with POI (40% vs. 26.2%, <i>p</i> = .04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We show that pregnancy in women with TS, whether OD or spontaneously conceived, carries obstetric risks, and therefore, women with TS, considering pregnancy, should receive comprehensive pre-pregnancy counselling and optimal obstetric care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154317","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}
Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk.
Design, Patients and Measurements
This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre.
Results
Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%.
Conclusion
This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.
{"title":"Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency","authors":"Katharine Lazarus, Annabel Hayes, Kavita Narula, Debbie Papadopolou, Tricia M.-M. Tan, Karim Meeran, Sirazum Choudhury","doi":"10.1111/cen.15074","DOIUrl":"10.1111/cen.15074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Design, Patients and Measurements</h3>\u0000 \u0000 <p>This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen.15074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154349","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}
Ilknur Kurt, Metin Eser, Ahmet Kahveci, Ahmet Ucar, Derya Bulus, Bahar Ozcabi, Omer Guran, Selen Karagozlu, Aysenur Ersoy, Senol Demir, Bilge Geckinli, Tulay Guran
Background
Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI).
Patients and Methods
Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined.
Results
Patients (n = 6, 4 females) were presented with severe hyperpigmentation (n = 6), hypoglycemia (n = 4), hyponatremia (n = 3), hyperkalemia (n = 1), respiratory distress syndrome (n = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05−0.85). Molecular studies revealed biallelic mutations in the MC2R (n = 4; 3 homozygous, 1 compound heterozygous), MRAP (n = 1) and STAR (n = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established.
Conclusion
Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a ‘normal’ screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.
{"title":"Severe adrenal insufficiency in six neonates with normal newborn screening for CAH","authors":"Ilknur Kurt, Metin Eser, Ahmet Kahveci, Ahmet Ucar, Derya Bulus, Bahar Ozcabi, Omer Guran, Selen Karagozlu, Aysenur Ersoy, Senol Demir, Bilge Geckinli, Tulay Guran","doi":"10.1111/cen.15080","DOIUrl":"10.1111/cen.15080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Newborn screening (NBS) reduces the risk of mortality in congenital adrenal hyperplasia (CAH), mainly due to the salt-wasting form of 21-hydroxylase deficiency. There is limited knowledge regarding the results of NBS in non-CAH primary adrenal insufficiency (non-CAH PAI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>Clinical and NBS for CAH data of neonates who were diagnosed with non-CAH PAI between January and December 2022 were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients (<i>n</i> = 6, 4 females) were presented with severe hyperpigmentation (<i>n</i> = 6), hypoglycemia (<i>n</i> = 4), hyponatremia (<i>n</i> = 3), hyperkalemia (<i>n</i> = 1), respiratory distress syndrome (<i>n</i> = 1) between 3rd hour to 2 months of life. All had normal NBS results. The median first-tier 17-hydroxyprogesterone (17OHP) concentration in NBS for CAH was 0.14 ng/mL (range; 0.05−0.85). Molecular studies revealed biallelic mutations in the <i>MC2R</i> (<i>n</i> = 4; 3 homozygous, 1 compound heterozygous), <i>MRAP</i> (<i>n</i> = 1) and <i>STAR</i> (<i>n</i> = 1) genes. Glucocorticoid with or without mineralocorticoid replacement was initiated once the diagnosis of non-CAH PAI was established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Neonates with non-CAH PAI have always normal NBS due to persistently low 17OHP, even when these newborn infants are severely symptomatic for adrenal insufficiency. Clinicians should be alert for signs of adrenal insufficiency in neonates, even if the patient has a ‘normal’ screening for CAH, so as not to delay diagnosis and treatment. This fact should be kept in mind particularly in countries where these conditions are more common than elsewhere.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10346,"journal":{"name":"Clinical Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145865","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}
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