Bang Sun,Maria I Stamou,Sara L Stockman,Mark B Campbell,Lacey Plummer,Kathryn B Salnikov,Leman Damla Kotan,A Kemal Topaloglu,Fuki M Hisama,Erica E Davis,Stephanie B Seminara,Ravikumar Balasubramanian
CONTEXTSOX11 variants cause Coffin-Siris Syndrome (CSS), characterized by developmental delay, hypogonadotropic hypogonadism (HH), skeletal and facial defects.OBJECTIVETo examine the contribution of SOX11 variants to the pathogenesis of Idiopathic Hypogonadotropic Hypogonadism (IHH), a disorder caused by hypothalamic GnRH deficiency.SETTINGThe Reproductive Endocrine Unit and the Pediatric Endocrinology Division, Massachusetts General Hospital.PATIENTS OR OTHER PARTICIPANTSA cohort of 1810 unrelated IHH probands.INTERVENTIONSExome sequencing data from the entire cohort were examined for SOX11 rare single nucleotide variants (SNVs) [minor allele frequency in the gnomAD database <0.1%]. Rare SOX11 variant association testing was performed between the IHH and gnomAD population. Phenotyping of individuals harboring pathogenic/likely pathogenic SNVs (determined by the ACMG criteria) was performed.MAIN OUTCOMES/RESULTSFour pathogenic SOX11 SNVs were identified in 5 IHH probands. The IHH cohort was enriched for SOX11 protein truncating SNVs (frameshift/nonsense) across the entire protein (2 SNVs in 3 IHH cases [p.S303X (de-novo); p.S345Afs*13]; p 0.0004981) and for SOX11 missense SNVs within the SOX11-high-mobility group (HMG) domain (2 SNVs in 2 IHH cases p.G84D[de-novo]; p.P114S; p=0.00313922). The phenotypic spectrum of SOX11 variant carriers revealed additional endocrine defects including anosmic and normosmic forms of IHH, growth-hormone deficiency, pituitary and hypothalamic structural defects, and hypothyroidism. A pathogenic SOX11 SNV was also identified in a patient with functional HH (FHH, p.R100Q). CSS-associated features were present in 4/5 probands.CONCLUSIONSDeleterious SOX11 variants cause IHH and other pituitary hormone deficiencies, suggesting that the human SOX11-associated disorder may stem from both hypothalamic and pituitary level defects.
{"title":"Expanding the Spectrum of Endocrine Abnormalities Associated with SOX11-related Disorders.","authors":"Bang Sun,Maria I Stamou,Sara L Stockman,Mark B Campbell,Lacey Plummer,Kathryn B Salnikov,Leman Damla Kotan,A Kemal Topaloglu,Fuki M Hisama,Erica E Davis,Stephanie B Seminara,Ravikumar Balasubramanian","doi":"10.1210/clinem/dgae620","DOIUrl":"https://doi.org/10.1210/clinem/dgae620","url":null,"abstract":"CONTEXTSOX11 variants cause Coffin-Siris Syndrome (CSS), characterized by developmental delay, hypogonadotropic hypogonadism (HH), skeletal and facial defects.OBJECTIVETo examine the contribution of SOX11 variants to the pathogenesis of Idiopathic Hypogonadotropic Hypogonadism (IHH), a disorder caused by hypothalamic GnRH deficiency.SETTINGThe Reproductive Endocrine Unit and the Pediatric Endocrinology Division, Massachusetts General Hospital.PATIENTS OR OTHER PARTICIPANTSA cohort of 1810 unrelated IHH probands.INTERVENTIONSExome sequencing data from the entire cohort were examined for SOX11 rare single nucleotide variants (SNVs) [minor allele frequency in the gnomAD database <0.1%]. Rare SOX11 variant association testing was performed between the IHH and gnomAD population. Phenotyping of individuals harboring pathogenic/likely pathogenic SNVs (determined by the ACMG criteria) was performed.MAIN OUTCOMES/RESULTSFour pathogenic SOX11 SNVs were identified in 5 IHH probands. The IHH cohort was enriched for SOX11 protein truncating SNVs (frameshift/nonsense) across the entire protein (2 SNVs in 3 IHH cases [p.S303X (de-novo); p.S345Afs*13]; p 0.0004981) and for SOX11 missense SNVs within the SOX11-high-mobility group (HMG) domain (2 SNVs in 2 IHH cases p.G84D[de-novo]; p.P114S; p=0.00313922). The phenotypic spectrum of SOX11 variant carriers revealed additional endocrine defects including anosmic and normosmic forms of IHH, growth-hormone deficiency, pituitary and hypothalamic structural defects, and hypothyroidism. A pathogenic SOX11 SNV was also identified in a patient with functional HH (FHH, p.R100Q). CSS-associated features were present in 4/5 probands.CONCLUSIONSDeleterious SOX11 variants cause IHH and other pituitary hormone deficiencies, suggesting that the human SOX11-associated disorder may stem from both hypothalamic and pituitary level defects.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Alice W Maciel,Debora L S Danilovic,Ibere C Soares,Thais C Freitas,Jessica Okubo,Gustavo F C Fagundes,Felipe Freitas-Castro,Lucas S Santana,Augusto G Guimaraes,Vinicius F Calsavara,Felipe L Ledesma,Luciana A Castroneves,Fernando M A Coelho,Victor Srougi,Fabio Y Tanno,Jose L Chambo,Francisco C Carnevale,João V Silveira,Fernanda M Consolim-Colombo,Luiz A Bortolotto,Luciana P Brito,Maria Candida B V Fragoso,Luciano F Drager,Celso E Gomez-Sanchez,Ana Claudia Latronico,Berenice B Mendonca,Ana O Hoff,Madson Q Almeida
BACKGROUNDAldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group.METHODSWe conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage.RESULTSThe prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001).CONCLUSIONPTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.
背景醛固酮长期过量会诱发氧化应激和细胞增殖。方法 我们进行了一项倾向得分匹配病例对照研究，以调查动脉高血压（HT）患者的醛固酮过多与 PTC 之间的关系。我们对 137 名 PTC 和 HT 患者的 PA 进行了调查。对照组包括 137 名（1:1）年龄、性别和体重指数 (BMI) 匹配的 HT 患者。结果PTC 组 PA 患病率为 29.20%（95% 置信区间 [CI]，21.91%-37.68%），而未与 HT 分期相匹配的对照组 PA 患病率为 20.44%（95% 置信区间 [CI]，14.22%-28.35%）（P = 0.093）。虽然两组的 PA 患病率相似，但与高血压对照组（73%，P＜0.001）相比，PTC 组的重度 HT（III 期或耐受期）患病率（23%）明显较低。按 HT 分期匹配对照组后，PTC 组 PA 患病率明显高于高血压对照组（9.56%；95% CI，5.39%-16.1%，P <0.0001）。在多变量分析中，无论是在未匹配的高血压患者中（比值比 [OR] 4.74；95% CI，2.26-10.55；p< 0.001），还是在与 HT 分期匹配的患者中（比值比 [OR] 5.88，95% CI，2.79-13.37；p< 0.001），PTC 都与 PA 独立相关。因此，我们建议将 PTC 与 HT 之间的关联作为 PA 筛查的一项新建议，无论 HT 的严重程度如何。
{"title":"Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.","authors":"Ana Alice W Maciel,Debora L S Danilovic,Ibere C Soares,Thais C Freitas,Jessica Okubo,Gustavo F C Fagundes,Felipe Freitas-Castro,Lucas S Santana,Augusto G Guimaraes,Vinicius F Calsavara,Felipe L Ledesma,Luciana A Castroneves,Fernando M A Coelho,Victor Srougi,Fabio Y Tanno,Jose L Chambo,Francisco C Carnevale,João V Silveira,Fernanda M Consolim-Colombo,Luiz A Bortolotto,Luciana P Brito,Maria Candida B V Fragoso,Luciano F Drager,Celso E Gomez-Sanchez,Ana Claudia Latronico,Berenice B Mendonca,Ana O Hoff,Madson Q Almeida","doi":"10.1210/clinem/dgae653","DOIUrl":"https://doi.org/10.1210/clinem/dgae653","url":null,"abstract":"BACKGROUNDAldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group.METHODSWe conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage.RESULTSThe prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001).CONCLUSIONPTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PURPOSETo evaluate the efficacy and safety of current targeted drug therapies for radioiodine-refractory differentiated thyroid cancer (RR-DTC).METHODSThis was a meta-analysis of relevant randomized controlled trials (RCTs) and single-arm studies searched across PubMed, Embase, Cochranes, and Web of Sciences up to September 12, 2023. Stata15.0 software was used to assess overall survival (OS), progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and adverse effects (AEs). The Cochrane Bias Risk tool was used to assess literature quality and trial bias and RevMan 5.4 was used to generate a quality assessment map.RESULTSA total of 8 RCTs and 17 single-arm studies with 3,270 patients on 7 drugs-vandetanib, sorafenib, lenvatinib, cabozantinib, apatinib, donafenib, and anlotinib-were included. Targeted therapy with these drugs effectively prolonged PFS and OS in patients with RR-DTC with overall HRs of 0.35 (95% CI 0.23-0.53, P < 0.00001) and 0.53 (95% CI 0.32-0.86, P < 0.00001), respectively. ORR and DCR were also prolonged, with overall RRs of 27.63 (95% CI 12.39-61.61, P<0.00001) and 1.66 (95% CI 1.48-1.86, P<0.00001), respectively. The subgroup analysis using Effect Size (ES) showed that apatinib had the best effect on ORR with an ES of 0.66 (95% CI 0.49-0.83, P<0.00001) and DCR with a ES of 0.95 (95% CI 0.91-1.00, P<0.00001). Common drug adverse effects included hypertension, diarrhea, proteinuria, and fatigue.CONCLUSIONThe currently used targeted drug therapies for RR-DTC can significantly improve clinical outcomes and the new drug apatinib demonstrates promise for potentially superior performance.
目的评估目前针对放射性碘难治性分化型甲状腺癌（RR-DTC）的靶向药物疗法的疗效和安全性。方法这是一项荟萃分析，研究对象是截至 2023 年 9 月 12 日在 PubMed、Embase、Cochranes 和 Web of Sciences 上搜索到的相关随机对照试验（RCT）和单臂研究。使用Stata15.0软件评估总生存期（OS）、无进展生存期（PFS）、疾病控制率（DCR）、客观反应率（ORR）和不良反应（AEs）。结果共纳入了8项RCT和17项单臂研究，3270名患者使用了7种药物--万德他尼、索拉非尼、伦伐替尼、卡博赞替尼、阿帕替尼、多纳非尼和安洛替尼。这些药物的靶向治疗有效延长了RR-DTC患者的PFS和OS，总HR分别为0.35（95% CI 0.23-0.53，P < 0.00001）和0.53（95% CI 0.32-0.86，P < 0.00001）。ORR和DCR也有所延长，总RR分别为27.63（95% CI 12.39-61.61，P<0.00001）和1.66（95% CI 1.48-1.86，P<0.00001）。使用效应大小（ES）进行的亚组分析显示，阿帕替尼对ORR的效应最佳，ES为0.66（95% CI 0.49-0.83，P<0.00001），对DCR的效应最佳，ES为0.95（95% CI 0.91-1.00，P<0.00001）。常见的药物不良反应包括高血压、腹泻、蛋白尿和乏力。结论目前用于 RR-DTC 的靶向药物疗法可显著改善临床疗效，而新药阿帕替尼有望取得更好的疗效。
{"title":"Efficacy and safety of targeted therapy for radioiodine-refractory differentiated thyroid cancer: a meta-analysis.","authors":"Yuqing Zhang,Xiaoxin Zhang,Lifan Lin,Mingzhao Xing","doi":"10.1210/clinem/dgae617","DOIUrl":"https://doi.org/10.1210/clinem/dgae617","url":null,"abstract":"PURPOSETo evaluate the efficacy and safety of current targeted drug therapies for radioiodine-refractory differentiated thyroid cancer (RR-DTC).METHODSThis was a meta-analysis of relevant randomized controlled trials (RCTs) and single-arm studies searched across PubMed, Embase, Cochranes, and Web of Sciences up to September 12, 2023. Stata15.0 software was used to assess overall survival (OS), progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and adverse effects (AEs). The Cochrane Bias Risk tool was used to assess literature quality and trial bias and RevMan 5.4 was used to generate a quality assessment map.RESULTSA total of 8 RCTs and 17 single-arm studies with 3,270 patients on 7 drugs-vandetanib, sorafenib, lenvatinib, cabozantinib, apatinib, donafenib, and anlotinib-were included. Targeted therapy with these drugs effectively prolonged PFS and OS in patients with RR-DTC with overall HRs of 0.35 (95% CI 0.23-0.53, P < 0.00001) and 0.53 (95% CI 0.32-0.86, P < 0.00001), respectively. ORR and DCR were also prolonged, with overall RRs of 27.63 (95% CI 12.39-61.61, P<0.00001) and 1.66 (95% CI 1.48-1.86, P<0.00001), respectively. The subgroup analysis using Effect Size (ES) showed that apatinib had the best effect on ORR with an ES of 0.66 (95% CI 0.49-0.83, P<0.00001) and DCR with a ES of 0.95 (95% CI 0.91-1.00, P<0.00001). Common drug adverse effects included hypertension, diarrhea, proteinuria, and fatigue.CONCLUSIONThe currently used targeted drug therapies for RR-DTC can significantly improve clinical outcomes and the new drug apatinib demonstrates promise for potentially superior performance.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"216 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabyan Esberard de Lima Beltrão,Giulia Carvalhal,Daniele Carvalhal de Almeida Beltrão,Fabricia Elisabeth de Lima Beltrão,Miriam O Ribeiro,Matthew D Ettleson,Helton Estrela Ramos,Antonio C Bianco
INTRODUCTIONLevothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of the L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE).GOALTo assess patient preferences in the treatment of hypothyroidism.METHODSA systematic review, meta-analysis, meta-regression, and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs. L-T4+L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by four researchers.RESULTSEleven RCTs (eight cross-over studies) with a total of 1,135 patients were considered. Overall, 24% of patients preferred L-T4 versus 52 % who preferred L-T4+L-T3 or DTE; 24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (RR: 2.20, 95% CI: 1.38 to 3.52; p = 0.0009). Excluding four studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97, 95% CI: 1.52 to 2.54; p < 0.00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84, 95% CI: 1.50 to 5.39; p < 0.00001). Network meta-analysis confirmed the preference for DTE and L-T3+L-T4 versus L-T4 alone.CONCLUSIONPatients with hypothyroidism prefer combination therapy (L-T3+L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism.
{"title":"Treatment Preferences in Patients with Hypothyroidism: an Analysis of Eleven Randomized Controlled Trials.","authors":"Fabyan Esberard de Lima Beltrão,Giulia Carvalhal,Daniele Carvalhal de Almeida Beltrão,Fabricia Elisabeth de Lima Beltrão,Miriam O Ribeiro,Matthew D Ettleson,Helton Estrela Ramos,Antonio C Bianco","doi":"10.1210/clinem/dgae651","DOIUrl":"https://doi.org/10.1210/clinem/dgae651","url":null,"abstract":"INTRODUCTIONLevothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of the L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE).GOALTo assess patient preferences in the treatment of hypothyroidism.METHODSA systematic review, meta-analysis, meta-regression, and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs. L-T4+L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by four researchers.RESULTSEleven RCTs (eight cross-over studies) with a total of 1,135 patients were considered. Overall, 24% of patients preferred L-T4 versus 52 % who preferred L-T4+L-T3 or DTE; 24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (RR: 2.20, 95% CI: 1.38 to 3.52; p = 0.0009). Excluding four studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97, 95% CI: 1.52 to 2.54; p < 0.00001; I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84, 95% CI: 1.50 to 5.39; p < 0.00001). Network meta-analysis confirmed the preference for DTE and L-T3+L-T4 versus L-T4 alone.CONCLUSIONPatients with hypothyroidism prefer combination therapy (L-T3+L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolomics: A Promising Tool in the Prevention, Diagnosis, and Treatment of Obesity.","authors":"Marisa Censani,Suzanne Cuda","doi":"10.1210/clinem/dgae634","DOIUrl":"https://doi.org/10.1210/clinem/dgae634","url":null,"abstract":"","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Victoria R van Trigt,Leontine E H Bakker,Iris C M Pelsma,Ingrid M Zandbergen,Maaia M Jentus,Mark C Kruit,Olaf M Dekkers,Wouter R van Furth,Marco J T Verstegen,Nienke R Biermasz
PURPOSETo evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL).METHODSCohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.0 (10.0-24.8 months). HR-QoL was measured using the Leiden Bothers and Needs Pituitary (LBNQ-P) questionnaire. Data were described for all patients, and patients undergoing elective total resection, with additional subgroups of (a) patients undergoing a high-probability-first-total-resection, and (b) reoperations aiming for total resection.RESULTSOne hundred surgically treated patients with prolactinoma were included (72 female). Dopamine agonist intolerance was the most frequent indication (n=68). The surgical goal (debulking/total resection) was achieved in 90% of patients. Long-term complications occurred in 4% of patients. Seventy-eight patients underwent an elective total resection, achieving remission in 91%. The subsets of preoperatively estimated high-probability-first-total-resections (n=52), and reoperations (n=9), achieved remission in 92% and 89%, respectively. LBNQ-P Total Bothers and Total Needs scores improved significantly after surgery (p<0.001, Δ-3.4 (IQR -14.4- -0.9) and p=0.006, Δ-1.8 (IQR -11.9-1.3), respectively.CONCLUSIONHigh remission rates were achieved, improving HR-QoL, evidencing (repeat) prolactinoma surgery is effective in an experienced pituitary center, as highlighted in the most recent guideline (2023).
{"title":"The changing treatment paradigm in prolactinoma - a prospective series of 100 consecutive neurosurgical cases.","authors":"Victoria R van Trigt,Leontine E H Bakker,Iris C M Pelsma,Ingrid M Zandbergen,Maaia M Jentus,Mark C Kruit,Olaf M Dekkers,Wouter R van Furth,Marco J T Verstegen,Nienke R Biermasz","doi":"10.1210/clinem/dgae652","DOIUrl":"https://doi.org/10.1210/clinem/dgae652","url":null,"abstract":"PURPOSETo evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL).METHODSCohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.0 (10.0-24.8 months). HR-QoL was measured using the Leiden Bothers and Needs Pituitary (LBNQ-P) questionnaire. Data were described for all patients, and patients undergoing elective total resection, with additional subgroups of (a) patients undergoing a high-probability-first-total-resection, and (b) reoperations aiming for total resection.RESULTSOne hundred surgically treated patients with prolactinoma were included (72 female). Dopamine agonist intolerance was the most frequent indication (n=68). The surgical goal (debulking/total resection) was achieved in 90% of patients. Long-term complications occurred in 4% of patients. Seventy-eight patients underwent an elective total resection, achieving remission in 91%. The subsets of preoperatively estimated high-probability-first-total-resections (n=52), and reoperations (n=9), achieved remission in 92% and 89%, respectively. LBNQ-P Total Bothers and Total Needs scores improved significantly after surgery (p<0.001, Δ-3.4 (IQR -14.4- -0.9) and p=0.006, Δ-1.8 (IQR -11.9-1.3), respectively.CONCLUSIONHigh remission rates were achieved, improving HR-QoL, evidencing (repeat) prolactinoma surgery is effective in an experienced pituitary center, as highlighted in the most recent guideline (2023).","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masanobu Kawai,Sachiko Baba,Kanami Tanigawa,Satoyo Ikehara,Ryo Kawasaki,Hiroyasu Iso
CONTEXTAdequate nighttime sleep duration has been considered beneficial for linear growth in children; however, there is limited and conflicting evidence regarding the association between sleep duration and subsequent linear growth.OBJECTIVETo investigate the association between sleep duration at 1.5 years and height at 3 years of age.METHODSThe Japan Environment and Children's Study is a nationwide prospective birth cohort study. Data from 52,140 term singleton births born at an appropriate-for-gestational age without background disorders that could potentially affect linear growth in the analyses were included. Nighttime and total sleep durations were calculated based on a self-administered questionnaire completed by caregivers. Tall stature was defined as height at or above the 75th percentile among participants.RESULTSAfter adjustment for height at 1.5 years, sex, monthly age, mother's height, presence of siblings at 1.5 years, environmental tobacco smoke at 1.5 years, daily TV/DVD screen time at 2 years, attendance at nursery at 2 years, household annual income at birth, and parents' educational status, multivariate odds ratio (95% confidence interval) for tall stature at 3 years were 1.09 (1.01-1.17), 1.09 (1.01-1.17), and 1.25 (1.14-1.37) for 9.5 or 10, 10.5 or 11, and ≥ 11.5 h of nighttime sleep duration at 1.5 years, respectively, compared with those with ≤ 9 h sleep (p for trend <0.0001). Total sleep duration was not associated with tall stature.CONCLUSIONThis study underscores the importance of nighttime sleep duration, not total sleep duration, in the linear growth of very young children.
{"title":"Association of nighttime sleep duration at 1.5 years with height at 3 years: The Japan Environment and Children's Study.","authors":"Masanobu Kawai,Sachiko Baba,Kanami Tanigawa,Satoyo Ikehara,Ryo Kawasaki,Hiroyasu Iso","doi":"10.1210/clinem/dgae647","DOIUrl":"https://doi.org/10.1210/clinem/dgae647","url":null,"abstract":"CONTEXTAdequate nighttime sleep duration has been considered beneficial for linear growth in children; however, there is limited and conflicting evidence regarding the association between sleep duration and subsequent linear growth.OBJECTIVETo investigate the association between sleep duration at 1.5 years and height at 3 years of age.METHODSThe Japan Environment and Children's Study is a nationwide prospective birth cohort study. Data from 52,140 term singleton births born at an appropriate-for-gestational age without background disorders that could potentially affect linear growth in the analyses were included. Nighttime and total sleep durations were calculated based on a self-administered questionnaire completed by caregivers. Tall stature was defined as height at or above the 75th percentile among participants.RESULTSAfter adjustment for height at 1.5 years, sex, monthly age, mother's height, presence of siblings at 1.5 years, environmental tobacco smoke at 1.5 years, daily TV/DVD screen time at 2 years, attendance at nursery at 2 years, household annual income at birth, and parents' educational status, multivariate odds ratio (95% confidence interval) for tall stature at 3 years were 1.09 (1.01-1.17), 1.09 (1.01-1.17), and 1.25 (1.14-1.37) for 9.5 or 10, 10.5 or 11, and ≥ 11.5 h of nighttime sleep duration at 1.5 years, respectively, compared with those with ≤ 9 h sleep (p for trend <0.0001). Total sleep duration was not associated with tall stature.CONCLUSIONThis study underscores the importance of nighttime sleep duration, not total sleep duration, in the linear growth of very young children.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CONTEXTDifferent fat depots have connected to cardiovascular health.OBJECTIVEWe assessed the associations of abdominal magnetic resonance-quantified visceral adipose tissue (VAT) and liver fat (proton density fat fraction, PDFF) with cardiac magnetic resonance (CMR)-measured cardiac structure and function, and considered potential mechanism.METHODSOur study encompassed 10,920 participants from the UK Biobank. We utilized multiple linear regression and multiple mediation analyses to estimate the connections between VAT or PDFF and CMR metrics.RESULTSElevated VAT or PDFF exhibited associations with adverse left ventricular (LV) structure (increased wall thickness, concentric LV remodeling), impaired LV function (lower LV global functional index, absolute value of LV global longitudinal strain), and diminished left atrial volumes and stroke volume (all p-values were significant）. Upon stratifying participants based on VAT and PDFF combinations, all groups, except the low VAT-low PDFF group, were linked to unfavorable cardiac remodeling metrics. The high VAT-high PDFF group displayed the most pronounced cardiac alterations. Multiple mediation analyses were employed to investigate potential mediating roles of systolic blood pressure (SBP), diabetes, dyslipidemia and blood biomarkers (lipidemia, transaminases) in the adipose-CMR relationship. The findings suggested that VAT or PDFF was related to SBP, diabetes, dyslipidemia, lipid profile, liver function, and glucose. Several potential mediating pathways were identified, primarily through SBP and triglyceride-glucose index, which only partially explained the adipose-CMR relationship.CONCLUSIONWe established the independent associations of VAT and PDFF with unhealthy cardiac structure and function. Furthermore, it identifies SBP and insulin resistance as important mediating factors.
{"title":"Associations between visceral and liver fat and cardiac structure and function: a UK Biobank study.","authors":"Zhi Lv,Yangzhi Fu,Yao Ma,Chang Liu,Miao Yuan,Dengfeng Gao","doi":"10.1210/clinem/dgae639","DOIUrl":"https://doi.org/10.1210/clinem/dgae639","url":null,"abstract":"CONTEXTDifferent fat depots have connected to cardiovascular health.OBJECTIVEWe assessed the associations of abdominal magnetic resonance-quantified visceral adipose tissue (VAT) and liver fat (proton density fat fraction, PDFF) with cardiac magnetic resonance (CMR)-measured cardiac structure and function, and considered potential mechanism.METHODSOur study encompassed 10,920 participants from the UK Biobank. We utilized multiple linear regression and multiple mediation analyses to estimate the connections between VAT or PDFF and CMR metrics.RESULTSElevated VAT or PDFF exhibited associations with adverse left ventricular (LV) structure (increased wall thickness, concentric LV remodeling), impaired LV function (lower LV global functional index, absolute value of LV global longitudinal strain), and diminished left atrial volumes and stroke volume (all p-values were significant）. Upon stratifying participants based on VAT and PDFF combinations, all groups, except the low VAT-low PDFF group, were linked to unfavorable cardiac remodeling metrics. The high VAT-high PDFF group displayed the most pronounced cardiac alterations. Multiple mediation analyses were employed to investigate potential mediating roles of systolic blood pressure (SBP), diabetes, dyslipidemia and blood biomarkers (lipidemia, transaminases) in the adipose-CMR relationship. The findings suggested that VAT or PDFF was related to SBP, diabetes, dyslipidemia, lipid profile, liver function, and glucose. Several potential mediating pathways were identified, primarily through SBP and triglyceride-glucose index, which only partially explained the adipose-CMR relationship.CONCLUSIONWe established the independent associations of VAT and PDFF with unhealthy cardiac structure and function. Furthermore, it identifies SBP and insulin resistance as important mediating factors.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lachlan M Angus,Shalem Y Leemaqz,Anna K Kasielska-Trojan,Maksym Mikołajczyk,James C G Doery,Jeffrey D Zajac,Ada S Cheung
CONTEXTTransgender people with sex recorded male at birth desiring feminization commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol, but the optimal anti-androgen is unclear.OBJECTIVETo assess the effect of anti-androgens on breast development. We hypothesized this would be greater in those treated with cyproterone acetate than spironolactone due to more potent androgen receptor antagonism and suppression of serum total testosterone concentrations.DESIGNRandomised clinical trial 2020-2022.SETTINGOutpatient endocrinology clinic.PARTICIPANTSTransgender people aged 18+ years old commencing feminizing gender affirming hormone therapy.INTERVENTIONSStandardized estradiol therapy plus either spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months.MAIN OUTCOME MEASURESPrimary outcome was breast development as measured by the breast chest distance. Secondary outcomes included estimated breast volume, suppression of serum total testosterone concentration <2nmol/L and Gender Preoccupation and Stability Questionnaire (GPSQ).RESULTSSixty-three people (median age 25 years) were enrolled, randomized and included in intention-to-treat analysis (cyproterone acetate n=32, spironolactone n=31). At six months, there was no between-group difference in breast chest distance (mean difference 0.27 cm, 95% CI -0.82 to 1.35, p=0.6) or estimated breast volume (mean difference 17.26 mL, 95% CI -16.94 to 51.47, p=0.3). Cyproterone acetate was more likely to suppress serum testosterone concentration to <2 nmol/L (odds ratio 9.01, 95% CI 1.83 to 4.44, p=0.008). Changes in GPSQ were similar between groups.CONCLUSIONAnti-androgen choice should be based on clinician and patient preference with consideration of side effects. Further research is needed to optimize breast development in transgender people.
{"title":"Effect of spironolactone and cyproterone acetate on breast growth in transgender people: a randomized clinical trial.","authors":"Lachlan M Angus,Shalem Y Leemaqz,Anna K Kasielska-Trojan,Maksym Mikołajczyk,James C G Doery,Jeffrey D Zajac,Ada S Cheung","doi":"10.1210/clinem/dgae650","DOIUrl":"https://doi.org/10.1210/clinem/dgae650","url":null,"abstract":"CONTEXTTransgender people with sex recorded male at birth desiring feminization commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol, but the optimal anti-androgen is unclear.OBJECTIVETo assess the effect of anti-androgens on breast development. We hypothesized this would be greater in those treated with cyproterone acetate than spironolactone due to more potent androgen receptor antagonism and suppression of serum total testosterone concentrations.DESIGNRandomised clinical trial 2020-2022.SETTINGOutpatient endocrinology clinic.PARTICIPANTSTransgender people aged 18+ years old commencing feminizing gender affirming hormone therapy.INTERVENTIONSStandardized estradiol therapy plus either spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months.MAIN OUTCOME MEASURESPrimary outcome was breast development as measured by the breast chest distance. Secondary outcomes included estimated breast volume, suppression of serum total testosterone concentration <2nmol/L and Gender Preoccupation and Stability Questionnaire (GPSQ).RESULTSSixty-three people (median age 25 years) were enrolled, randomized and included in intention-to-treat analysis (cyproterone acetate n=32, spironolactone n=31). At six months, there was no between-group difference in breast chest distance (mean difference 0.27 cm, 95% CI -0.82 to 1.35, p=0.6) or estimated breast volume (mean difference 17.26 mL, 95% CI -16.94 to 51.47, p=0.3). Cyproterone acetate was more likely to suppress serum testosterone concentration to <2 nmol/L (odds ratio 9.01, 95% CI 1.83 to 4.44, p=0.008). Changes in GPSQ were similar between groups.CONCLUSIONAnti-androgen choice should be based on clinician and patient preference with consideration of side effects. Further research is needed to optimize breast development in transgender people.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: \"The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia-Subanalysis of the DALI Study\".","authors":"","doi":"10.1210/clinem/dgae641","DOIUrl":"https://doi.org/10.1210/clinem/dgae641","url":null,"abstract":"","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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