記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：eBioMedicine  

BACKGROUND: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. METHODS: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. FINDINGS: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. INTERPRETATION: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. FUNDING: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.

DOI： 10.1016/j.ebiom.2024.105087

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Lipid Research  

Quantitative information on blood metabolites can be used in developing advanced medical strategies such as early detection and prevention of disease. Monitoring bioactive lipids such as steroids, bile acids, and PUFA metabolites could be a valuable indicator of health status. However, a method for simultaneously measuring these bioactive lipids has not yet been developed. Here, we report a LC/MS/MS method that can simultaneously measure 144 bioactive lipids, including steroids, bile acids, and PUFA metabolites, from human plasma, and a sample preparation method for these targets. Protein removal by methanol precipitation and purification of bioactive lipids by solid-phase extraction improved the recovery of the targeted compounds in human plasma samples, demonstrating the importance of sample preparation methods for a wide range of bioactive lipid analyses. Using the developed method, we studied the plasma from healthy human volunteers and confirmed the presence of bioactive lipid molecules associated with sex differences and circadian rhythms. The developed method of bioactive lipid analysis can be applied to health monitoring and disease biomarker discovery in precision medicine.

DOI： 10.1016/j.jlr.2023.100492

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記述言語：日本語   出版者・発行元：(公財)上原記念生命科学財団  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1413207923

CiNii Research

記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：eBioMedicine  

Background: Autonomous cortisol secretion (ACS), resulting from cortisol-producing adenomas (CPA), causes endogenous steroid-induced osteoporosis (SIOP). However, the risk of endogenous SIOP cannot be explained by cortisol excess alone, and how other steroid metabolites affect bone status is unclear. Methods: ACS was diagnosed as serum cortisol ≥1.8 μg/dL after the 1-mg dexamethasone suppression test (DST-cortisol). Using liquid chromatography tandem mass spectrometry, 21 plasma steroid metabolites were measured in 73 patients with ACS and 85 patients with non-functioning adrenal tumors (NFAT). Expression of steroidogenic enzymes and relevant steroid metabolites were analyzed in some of CPA tissues. Findings: Discriminant and principal component analyses distinguished steroid profiles between the ACS and NFAT groups in premenopausal women. Premenopausal women with ACS exhibited higher levels of a mineralocorticoid metabolite, 11-deoxycorticosterone (11-DOC), and lower levels of androgen metabolites, dehydroepiandrosterone-sulfate, and androsterone-glucuronide. In premenopausal women with ACS, DST-cortisol negatively correlated with trabecular bone score (TBS). Additionally, 11-DOC negatively correlated with lumbar spine-bone mineral density, whereas androsterone-glucuronide positively correlated with TBS. The CPA tissues showed increased 11-DOC levels with increased expression of CYP21A2, essential for 11-DOC synthesis. Adrenal non-tumor tissues were atrophied with reduced expression of CYB5A, required for androgen synthesis. Interpretation: This study demonstrates that unbalanced production of adrenal steroid metabolites, derived from both adrenal tumor and non-tumor tissues, contributes to the pathogenesis of endogenous SIOP in premenopausal women with ACS. Funding: JSPS KAKENHI, Secom Science and Technology Foundation, Takeda Science Foundation, Japan Foundation for Applied Enzymology, AMED-CREST, JST A-STEP, JST-Moonshot, and Ono Medical Research Foundation.

DOI： 10.1016/j.ebiom.2023.104733

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. METHODS: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. RESULTS: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell's C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. CONCLUSIONS: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.

DOI： 10.1007/s00535-023-01987-8

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

切除した膵神経内分泌腫瘍(PanNEN)は再発率が高いので、その予測因子を検索した。22医療機関で1987年1月～2020年7月に切除したPanNEN573例のデータベースを作成した。局在性の非機能性膵神経内分泌腫瘍(G1/G2)の371名の患者の臨床的特徴を分析した。再発を決定付ける特徴を分析するため、機械学習予測モデルを構築した。経過観察中に患者52名に再発がみられ、再発までの中央値は33.7ヵ月であった。ランダムサバイバルフォレスト(RSF)モデルはCox比例ハザード回帰モデルよりもHarrell C指数が優れていた。Ki-67指数、残存腫瘍、WHOグレード、腫瘍サイズ、リンパ節転移がRSFモデルの上位5予測因子で、腫瘍サイズ20mm以上が再発の可能性の上昇する分岐点で、Ki-67指数の上昇とともに5年無増悪生存率が直線的に低下した。

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：その他   出版者・発行元：Cold Spring Harbor Laboratory  

Abstract

Quantitative information on blood metabolites has the potential to be utilized in medical strategies such as early disease detection and prevention. Monitoring of bioactive lipids, such as steroids, bile acids, and polyunsaturated fatty acid (PUFA) metabolites, could be a valuable indicator for health status. However, a method for simultaneous measurement of these bioactive lipids has not been reported at present. Here, we report a liquid chromatography tandem mass spectrometry (LC/MS/MS) method that can simultaneously measure more than 140 bioactive lipids, including steroids, bile acids, and PUFA metabolites, from human plasma, and a sample preparation method for these targets. Protein removal in methanol precipitation and purification operations of bioactive lipids by solid-phase extraction improved the recovery of targeted compounds in human plasma samples, demonstrating the importance of sample preparation methods in a wide range of bioactive lipid analyses. Using the developed method, we measured plasma from healthy human volunteers and confirmed the presence of bioactive lipid molecules associated with sex differences and circadian rhythms. The practical bioactive lipid analysis method developed is expected to be applied to health monitoring and disease biomarker discovery for precision medicine.

DOI： 10.1101/2023.04.13.536679

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bone Reports  

Purpose: Bone and vascular diseases are considered to share pathogenic mechanisms. Excess glucocorticoids, key regulators of cardiovascular and metabolic homeostasis, may promote both diseases simultaneously. We used endogenous Cushing's syndrome (CS) to investigate whether glucocorticoid excess underlies coexisting bone and vascular diseases. Methods: We included 194 patients with adrenal tumors (ATs): autonomous cortisol secretion (ACS, n = 97) and non-functional AT (n = 97). ACS was further classified into overt CS (n = 17) and subclinical CS (SCS, n = 80). Arterial stiffness was defined as a brachial-ankle pulse wave velocity (baPWV) ≥ 1800 cm/s. Results: Patients with ACS had higher coexistence rates of vertebral fracture and arterial stiffness (23 % vs. 2 %; p < 0.001) and vertebral fracture and abdominal aortic calcification (22 % vs. 1 %; p < 0.001) than those with non-functional AT. In patients with ACS, baPWV was negatively correlated with trabecular bone score (TBS, r = -0.33; p = 0.002), but not with bone mineral density, and vertebral fracture was associated with arterial stiffness in the logistic regression analysis. In the multivariate analysis of variance, the degree of cortisol excess (defined as CS, SCS, and non-functional AT) determined the correlation between TBS and baPWV (partial η2 = 0.07; p < 0.001). In the analysis of covariance, patients with coexisting vertebral fracture and arterial stiffness had higher levels of serum cortisol after the 1-mg dexamethasone suppression test than those without. Conclusion: In endogenous glucocorticoid excess, bone and vascular diseases frequently coexisted, and deteriorated bone quality, not bone loss, was related to arterial stiffness. Thus, glucocorticoid excess may perturb the bone-vascular axis.

DOI： 10.1016/j.bonr.2022.101610

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Endocrinology  

OBJECTIVE: The clinical practice guideline for primary aldosteronism (PA) places a high value on confirmatory tests to sparing patients with false-positive results in case detection from undergoing adrenal venous sampling (AVS). However, it is unclear whether multiple types of confirmatory tests are more useful than a single type. To evaluate whether the machine-learned combination of two confirmatory tests is more useful in predicting subtypes of PA than each test alone. DESIGN: A retrospective cross-sectional study in referral centres. PATIENTS: This study included 615 patients with PA randomly assigned to the training and test data sets. The participants underwent saline infusion test (SIT) and captopril challenge test (CCT) and were subtyped by AVS (unilateral, n = 99; bilateral, n = 516). MEASUREMENTS: The area under the curve (AUC) and clinical usefulness using decision curve analysis for the subtype prediction in the test data set. RESULTS: The AUCs for the combination of SIT and CCT, SIT alone and CCT alone were 0.850, 0.813 and 0.786, respectively, with no significant differences between them. The AUC for the baseline clinical characteristics alone was 0.872, whereas the AUCs for these combined with SIT, combined with CCT and combined with both SIT and CCT were 0.868, 0.854 and 0.855, respectively, with no significant improvement in AUC. The additional clinical usefulness of the second confirmatory test was unremarkable on decision curve analysis. CONCLUSIONS: Our data suggest that patients with positive case detection undergo one confirmatory test to determine the indication for AVS.

DOI： 10.1111/cen.14854

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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出版者・発行元：Hypertension Research  

A recent report stated that patients with primary aldosteronism who remain renin suppressed during mineralocorticoid receptor antagonist treatment might have a higher risk of developing cardiovascular disease than those with unsuppressed renin activity. We retrospectively investigated the incidence of composite cardiovascular disease and risk factors for cardiovascular disease in 1115 Japanese patients with primary aldosteronism treated with mineralocorticoid receptor antagonists. The median follow-up period was 3.0 years, and the incidence of cardiovascular events was very low (2.1%) throughout 5 years of follow-up. Changes in plasma renin activity from before to after mineralocorticoid receptor antagonist treatment were divided into three groups based on tertile, low, intermediate, and high plasma renin activity change groups, with incidences of cardiovascular disease events of 2.1%, 0.5%, and 3.7%, respectively. Multivariate Cox regression analysis revealed age (adjusted hazard ratio, 1.07; 95% confidence interval, [1.02–1.12]) and body mass index (adjusted hazard ratio, 1.13 [1.04–1.23]) as independent risk factors for cardiovascular disease. The high plasma renin activity change group had significantly higher cardiovascular disease risk with mineralocorticoid receptor antagonist treatment than the intermediate plasma renin activity change group (adjusted hazard ratio, 5.71 [1.28–25.5]). These data suggest that a high change in renin level after mineralocorticoid receptor antagonist treatment may not necessarily predict a better prognosis of cardiovascular disease in patients with primary aldosteronism.

DOI： 10.1038/s41440-022-00960-x

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：iScience  

Despite recent therapeutic advances for multiple myeloma (MM), relapse is very common. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of MM cells from a patient with relapsed MM, treated with multiple anti-myeloma drugs. We observed five subclusters of MM cells, which appeared and/or disappeared in response to the therapeutic pressure, and identified cluster 3 which emerged during lenalidomide treatment and disappeared after proteasome inhibitor (PI) treatment. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin-protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death in in vitro assay. Kaplan-Meier survival analysis of database revealed that higher expression of PELI2 is associated with a better prognosis. Our integrated strategy combining longitudinal scRNA-seq analysis, in vitro functional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug-response genes.

DOI： 10.1016/j.isci.2022.104781

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Endocrinology and Metabolism  

CONTEXT: The adrenal cortex consists of zona glomerulosa (ZG), fasciculata (ZF), and reticularis. Aldosterone-producing cell clusters that strongly express aldosterone synthase (CYP11B2) are frequently found in adult adrenals and harbor somatic mutations that are also detected in aldosterone-producing adenomas (APAs). Primary aldosteronism is mainly caused by APAs or idiopathic hyperaldosteronism (IHA). We presume that APCCs are causing IHA and are precursors of APAs. However, the gene expression characteristics and especially the development of APCC are not well understood. OBJECTIVE: This study aimed to analyze the transcriptome of APCC at single-cell resolution and infer the developmental trajectory. METHODS: Single-cell RNA sequencing (scRNA-seq) of two adult adrenals was performed. RESULTS: Immunohistochemical analyses confirmed the two adrenals had APCCs. scRNA-seq data of 2,928 adrenal cells were obtained and 1,765 adrenocortical cells were identified based on unsupervised clustering and the marker gene expression. The adrenocortical cells were divided into 6 clusters, of which three clusters (923 cells) were composed of APCC/ZG cells. By further sub-clustering, the APCC/ZG cells were divided into three clusters (clusters C1, C2, and C3), we finally identified APCC-cluster (C3) and ZG-cluster (C1). Cluster C2 seemed to be ZG-to-ZF transitional cells. RNA velocity analysis inferred the developmental direction from cluster ZG-cluster-C1 to APCC-cluster-C3. The scRNA-seq additionally revealed that many CYP11B2-positive cells were positive for CYP11B1 and/or CYP17A1, which were essential for cortisol but not for aldosterone production. CONCLUSIONS: Our results revealed the gene expression characteristics of APCC at single-cell resolution and show that some ZG cells remodel to APCC.

DOI： 10.1210/clinem/dgac394

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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出版者・発行元：株式会社医学書院  

DOI： 10.11477/mf.1542203029

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記述言語：日本語  

＜文献概要＞Point ●原発性アルドステロン症とCushing症候群の診断は,それぞれアルドステロン産生とコルチゾール産生の調節メカニズムを利用する内分泌検査所見に基づく.●アルドステロンとコルチゾールの産生病変の病理診断には,それぞれの合成経路に特異的な酵素であるCYP11B2とCYP11B1の免疫組織化学的検出が行われる.●アルドステロンの過剰産生細胞には,KCNJ5遺伝子変異などの細胞内カルシウム濃度上昇をきたす遺伝子変異が知られる.●コルチゾールの過剰産生細胞には,PRKACA遺伝子変異などの細胞内サイクリックAMPの濃度上昇をきたす遺伝子変異が知られる.

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞Point ●原発性アルドステロン症とCushing症候群の診断は,それぞれアルドステロン産生とコルチゾール産生の調節メカニズムを利用する内分泌検査所見に基づく.●アルドステロンとコルチゾールの産生病変の病理診断には,それぞれの合成経路に特異的な酵素であるCYP11B2とCYP11B1の免疫組織化学的検出が行われる.●アルドステロンの過剰産生細胞には,KCNJ5遺伝子変異などの細胞内カルシウム濃度上昇をきたす遺伝子変異が知られる.●コルチゾールの過剰産生細胞には,PRKACA遺伝子変異などの細胞内サイクリックAMPの濃度上昇をきたす遺伝子変異が知られる.

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記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Unilateral subtype of primary aldosteronism (PA) is a common surgically curable form of endocrine hypertension. However, more than half of the patients with PA who undergo unilateral adrenalectomy suffer from persistent hypertension, which may discourage those with PA from undergoing adrenalectomy even when appropriate. The aim of this retrospective cross-sectional study was to develop machine learning-based models for predicting postoperative hypertensive remission using preoperative predictors that are readily available in routine clinical practice. A total of 107 patients with PA who achieved complete biochemical success after adrenalectomy were included and randomly assigned to the training and test datasets. Predictive models of complete clinical success were developed using supervised machine learning algorithms. Of 107 patients, 40 achieved complete clinical success after adrenalectomy in both datasets. Six clinical features associated with complete clinical success (duration of hypertension, defined daily dose (DDD) of antihypertensive medication, plasma aldosterone concentration (PAC), sex, body mass index (BMI), and age) were selected based on predictive performance in the machine learning-based model. The predictive accuracy and area under the curve (AUC) for the developed model in the test dataset were 77.3% and 0.884 (95% confidence interval: 0.737-1.000), respectively. In an independent external cohort, the performance of the predictive model was found to be comparable with an accuracy of 80.4% and AUC of 0.867 (95% confidence interval: 0.763-0.971). The duration of hypertension, DDD of antihypertensive medication, PAC, and BMI were non-linearly related to the prediction of complete clinical success. The developed predictive model may be useful in assessing the benefit of unilateral adrenalectomy and in selecting surgical treatment and antihypertensive medication for patients with PA in clinical practice.

DOI： 10.1038/s41598-022-09706-8

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   出版者・発行元：(一社)日本内分泌学会  

副腎摘除術が施行された片側原発性アルドステロン症患者59例(男性34例、中央値46.0歳)を対象とした後向き研究を実施し、術後の生化学的および臨床的転帰を術後10日以内に得られた検査所見に基づき評価した。評価項目は初期評価時(術後1～10日)および最終評価時(術後6～12ヵ月)の血漿アルドステロン濃度および血漿レニン活性とした。患者を最終評価時の生化学的転帰により、生化学的完全奏効群51例、生化学的部分奏効・非奏効群8例に分けて検討した。その結果、初回評価時の術後血漿アルドステロン濃度中央値は完全生化学的奏効群と比較して、生化学的部分奏効・非奏効群で有意に高値であったが(12.7ng/dL対6.3ng/dL、p<0.001)、他の因子に有意差は認められなかった。ROC解析の結果、生化学的転帰の予測における初回評価時の術後血漿アルドステロン濃度の至適カットオフ値は8.1ng/dL(感度76.5%、特異度100%)。以上から、術後血漿アルドステロン値低値であることは、原発性アルドステロン症の生化学的治癒を予測する可能性が示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Endocrinology and Metabolism  

Abstract

Context

Prolonged exposure to pathological cortisol, as in Cushing’s syndrome causes various age-related disorders, including sarcopenia. However, it is unclear whether mild cortisol excess, for example, accelerates sarcopenia due to aging or chronic stress.

Objective

We used Mendelian randomization (MR) analysis to assess whether cortisol was causally associated with muscle strength and mass.

Methods

Three single-nucleotide polymorphisms associated with plasma cortisol concentrations in the CORtisol NETwork consortium (n = 12 597) were used as instrumental variables. Summary statistics with traits of interest were obtained from relevant genome-wide association studies. For the primary analysis, we used the fixed-effects inverse-variance weighted analysis accounting for genetic correlations between variants.

Results

One SD increase in cortisol was associated with SD reduction in grip strength (estimate, −0.032; 95% CI −0.044 to −0.020; P = 3e-04), whole-body lean mass (estimate, −0.032; 95% CI, −0.046 to −0.017; P = 0.004), and appendicular lean mass (estimate, −0.031; 95% CI, −0.049 to −0.012; P = 0.001). The results were supported by the weighted-median analysis, with no evidence of pleiotropy in the MR-Egger analysis. The association of cortisol with grip strength and lean mass was observed in women but not in men. The association was attenuated after adjusting for fasting glucose in the multivariable MR analysis, which was the top mediator for the association in the MR Bayesian model averaging analysis.

Conclusion

This MR study provides evidence for the association of cortisol with reduced muscle strength and mass, suggesting the impact of cortisol on the development of sarcopenia.

DOI： 10.1210/clinem/dgab862

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その他リンク： https://academic.oup.com/jcem/article-pdf/107/4/e1477/42994589/dgab862.pdf

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers in Endocrinology  

Whole transcriptome profiling is a promising technique in adrenal studies; however, whole transcriptome profiling of adrenal disease using formalin-fixed paraffin-embedded (FFPE) samples has to be further explored. The aim of this study was to evaluate the utility of transcriptome data from FFPE samples of adrenocortical tumors. We performed whole transcriptome profiling of FFPE and fresh frozen samples of adrenocortical carcinoma (ACC, n = 3), aldosterone-producing adenoma (APA, n = 3), and cortisol-producing adenoma (CPA, n = 3), and examined the similarity between the transcriptome data. We further examined whether the transcriptome data of FFPE samples could be used to distinguish tumor types and detect marker genes. The number of read counts was smaller in FFPE samples than in fresh frozen samples (P < 0.01), while the number of genes detected was similar (P = 0.39). The gene expression profiles of FFPE and fresh frozen samples were highly correlated (r = 0.93, P < 0.01). Tumor types could be distinguished by consensus clustering and principal component analysis using transcriptome data from FFPE samples. In the differential expression analysis between ACC and APA-CPA, known marker genes of ACC (e.g., CCNB2, TOP2A, and MAD2L1) were detected in FFPE samples of ACC. In the differential expression analysis between APA and CPA, known marker genes of APA (e.g., CYP11B2, VSNL1, and KCNJ5) were detected in the APA of FFPE samples. The results suggest that FFPE samples may be a reliable alternative to fresh frozen samples for whole transcriptome profiling of adrenocortical tumors.

DOI： 10.3389/fendo.2022.808331

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Diabetes Investigation  

AIMS/INTRODUCTION: Diabetes mellitus is a major risk factor for the development of cardiovascular diseases. Heart failure with preserved ejection fraction is characterized by left ventricular diastolic dysfunction (LVDD). It has been reported that excess cortisol found in patients with Cushing's syndrome was associated with the development of LVDD. However, the relationship between cortisol concentration and LVDD in patients with diabetes mellitus has not been addressed. MATERIALS AND METHODS: We enrolled 109 patients with diabetes mellitus and 104 patients without diabetes mellitus who had undergone echocardiographic examination at Kyushu University Hospital, Fukuoka, Japan, between November 2016 and March 2019. Left ventricular function was evaluated and the ratio of early diastolic velocity from transmitral inflow to early diastolic velocity (E/e') was used as an index of diastolic function. Plasma cortisol concentrations, glycemic control, lipid profiles, treatment with antidiabetic drugs and other clinical characteristics were evaluated, and their associations with E/e' were determined using univariate and multivariate analyses. RESULTS: Multivariate linear regression analysis showed that log E/e' was positively correlated with age (P = 0.017), log systolic blood pressure (P = 0.004) and cortisol (P = 0.037), and negatively correlated with estimated glomerular filtration rate (P = 0.016) and the use of sodium-glucose cotransporter 2 inhibitors (P = 0.042) in patients with diabetes mellitus. Multivariate analysis showed that cortisol was positively correlated with age (P = 0.016) and glycated hemoglobin (P = 0.011). There was no association between E/e' and cortisol in patients without diabetes mellitus. CONCLUSIONS: Increased cortisol levels might increase the risk of developing LVDD in diabetes mellitus patients.

DOI： 10.1111/jdi.13653

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.13653

記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

糖尿病(DM)患者の左室拡張能障害に対する血中コルチゾール値の影響について検討した。対象は心エコー図検査を施行したDM患者109名と非DM患者104名である。拡張能の指標として拡張早期血流速度と僧帽弁輪部拡張早期速度の比(E/e')を算出し、各種臨床指標との関連を解析した。E/e'はDM群が非DM群に比べ高値であった(10.4 vs 8.3、P<0.001)。DM群の対数変換(log)E/e'は、年齢(β=0.22、P=0.017)、log収縮期血圧(β=0.25、P=0.004)、コルチゾール値(β=0.18、P=0.037)、推算糸球体濾過量(β=-0.21、P=0.016)、およびナトリウム・グルコース共輸送体2阻害薬使用(β=-0.18、P=0.042)と相関した。非DM群ではE/e'とコルチゾールの間に関連はみられなかった。DM患者のコルチゾール高値は、拡張能障害のリスク上昇と関連する可能性がある。

記述言語：英語   出版者・発行元：一般社団法人 日本内分泌学会  

In 2017, the Primary Aldosteronism Surgical Outcome (PASO) investigators proposed consensus criteria for clinical and biochemical outcomes. However, 6 to 12 months need to pass in order to assess for the outcome in patients who have undergone surgery for the management of primary hyperaldosteronism. This study aims to evaluate the post-operative biochemical and clinical outcomes of primary aldosteronism (PA) on the basis of the laboratory findings obtained within 10 days after surgery. We retrospectively studied 59 consecutive patients with unilateral PA who underwent adrenalectomy and were assessed for plasma aldosterone concentration (PAC) and plasma renin activity both at the initial assessment (1–10 days after surgery) and the final assessment (6–12 months after surgery). When comparing the complete biochemical success group (n = 51) and the partial or absent biochemical success group (n = 8), the median post-operative PAC at the initial assessment was significantly greater in the partial or absent biochemical success group (12.7 ng/dL; interquartile range [IQR], 10.6–14.5) than that in the complete biochemical success group (6.3 ng/dL; IQR, 5.0–7.9) (p < 0.001), while no significant differences were observed in other factors. The receiver operating characteristic curves of post-operative PAC at the initial assessment, which was used to predict biochemical outcomes, indicated that 8.1 ng/dL is the optimal PAC cut-off for biochemical success (sensitivity, 76.5%; specificity, 100%). Low post-operative PAC at the initial assessment may predict the biochemical cure of PA.

DOI： 10.1507/endocrj.ej21-0430

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Dehydroepiandrosterone sulfate (DHEAS) from the adrenal cortex substantially decreases with age, which may accelerate osteoporosis. However, the association of DHEAS with bone mineral density (BMD) and fracture is inconclusive. We conducted a Mendelian randomization (MR) analysis to investigate the role of DHEAS in age-related changes in BMD and fracture risk. METHODS: Single nucleotide polymorphisms (SNPs) associated with serum DHEAS concentrations were used as instrumental variables (4 SNPs for main analysis; 4 SNPs for men and 5 SNPs for women in sex-related analysis). Summary statistics were obtained from relevant genome-wide association studies. RESULTS: A log-transformed unit (μmol/L) increase in serum DHEAS concentrations was associated with SD increase in estimated BMD at the heel (estimate, 0.120; 95% confidence interval [CI], 0.081-0.158; P = 9 × 10 -10), and decreased fracture (odds ratio [OR], 0.989; 95%CI, 0.981-0.996; P = 0.005), consistent with dual-energy X-ray absorptiometry-derived BMD at the femoral neck and lumbar spine. Their associations remained even after adjusting for height, body mass index, testosterone, estradiol, sex hormone-binding globulin, and IGF-1. The association of DHEAS with fracture remained after adjusting for falls, grip strength, and physical activity but was attenuated after adjusting for BMD. The MR-Baysian model averaging analysis showed BMD was the top mediating factor for association of DHEAS with fracture. The association between DHEAS and BMD was observed in men but not in women. CONCLUSION: DHEAS was associated with increased BMD and decreased fracture. DHEAS may play a protective role in decreasing fracture risk, mainly by increasing bone mass.

DOI： 10.1210/clinem/dgab459

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Dehydroepiandrosterone sulfate (DHEAS) from the adrenal cortex substantially decreases with age, which may accelerate osteoporosis. However, the association of DHEAS with bone mineral density (BMD) and fracture is inconclusive. We conducted a Mendelian randomization (MR) analysis to investigate the role of DHEAS in age-related changes in BMD and fracture risk. METHODS: Single nucleotide polymorphisms (SNPs) associated with serum DHEAS concentrations were used as instrumental variables (4 SNPs for main analysis; 4 SNPs for men and 5 SNPs for women in sex-related analysis). Summary statistics were obtained from relevant genome-wide association studies. RESULTS: A log-transformed unit (µmol/L) increase in serum DHEAS concentrations was associated with an SD increase in estimated BMD at the heel (estimate, 0.120; 95% CI, 0.081-0.158; P = 9 × 10-10), and decreased fracture (odds ratio, 0.989; 95% CI, 0.981-0.996; P = 0.005), consistent with dual-energy X-ray absorptiometry-derived BMD at the femoral neck and lumbar spine. Their associations remained even after adjusting for height, body mass index, testosterone, estradiol, sex hormone-binding globulin, and insulin-like growth factor 1. The association of DHEAS with fracture remained after adjusting for falls, grip strength, and physical activity but was attenuated after adjusting for BMD. The MR-Bayesian model averaging analysis showed BMD was the top mediating factor for association of DHEAS with fracture. The association between DHEAS and BMD was observed in men but not in women. CONCLUSION: DHEAS was associated with increased BMD and decreased fracture. DHEAS may play a protective role in decreasing fracture risk, mainly by increasing bone mass.

DOI： 10.1210/clinem/dgab459

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.

DOI： 10.1038/s41598-021-88712-8

記述言語：日本語  

副腎皮質腫瘍を対象として、液体クロマトグラフィータンデム質量分析(LC/MS/MS)によるメタボロミクスを基盤とした腫瘍組織の統合解析から、副腎皮質腫瘍における代謝特性の多様性の成因を明らかにすることを目的とした。アルドステロン産生腫瘍、顕性コルチゾール産生腫瘍、不顕性コルチゾール産生腫瘍、非副腎皮質腫瘍を対象として、LC/MS/MSを用いて組織中のアルドステロン、コルチゾールの定量を行った。アルドステロンについては、アルドステロン産生腫瘍においてのみ有意な上昇がみられたが、コルチゾールにおいては、興味深いことにアルドステロン産生腫瘍は不顕性コルチゾール産生腫瘍と同定度のコルチゾール過剰分泌がみられた。アルドステロン産生腫瘍における、腫瘍内コルチゾール合成の局在を評価する目的で、代謝産物の可視化法として、最新技術であるイメージング質量顕微鏡を用いた解析を行った。免疫組織学染色のコルチゾール合成酵素(CYP11B1)の局在と一致して、コルチゾール合成が腫瘍内で均一的に行われることを同定した。アルドステロン産生腫瘍およびコルチゾール分泌が緩徐である、不顕性コルチゾール産生腫瘍を対象として、RNA-seqを施行した。315遺伝子に発現変動が確認され、予想通りAPAにおいてアルドステロン合成に関連するパスウェイがエンリッチされた。一方で、steroid metabolic processパスウェイ(27遺伝子)もエンリッチされていたが、コルチゾール合成に関連する遺伝子発現は両腫瘍において差異は検出されなかった。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pathological excess of fibroblast growth factor 23 (FGF23) causes mineral and bone disorders. However, the causality of FGF23 in the development of osteoporosis remains unknown. Whether FGF23 has systemic effects on cardiometabolic disorders beyond regulating mineral metabolism is also controversial. In this study, we investigated the causal effect of FGF23 on osteoporosis and cardiometabolic disorders using Mendelian randomization (MR) analysis. Summary statistics for single-nucleotide polymorphisms with traits of interest were obtained from the relevant genome-wide association studies. As a result, FGF23 was found to be inversely associated with femoral neck-BMD (odds ratio [OR] 0.682, 95% confidence interval [CI] 0.546-0.853, p = 8e-04) and heel estimated BMD (eBMD) (OR 0.898, 95%CI 0.820-0.985, p = 0.022) in the inverse-variance-weighted analysis, but not lumbar spine-BMD and fractures. The results were supported by the weighted-median analysis, and there was no evidence of pleiotropy in the MR-Egger analysis. FGF23 was associated with FN-BMD and eBMD after adjustment for estimated glomerular filtration rate, height, and body mass index in multivariable MR analysis. On the other hand, there was no association between FGF23 and cardiometabolic traits including cardio artery disease, brachial-ankle pulse wave velocity, intima-media thickness of carotid arteries, systolic and diastolic blood pressure, fasting glucose, high and low-density lipoprotein cholesterol, and triglycerides. Therefore, this MR study established that FGF23 was involved in bone loss and, in contrast, was not involved in cardiometabolic disorders. Our findings provide important insights into the role of FGF23 in the pathogenesis of osteoporosis and cardiometabolic disorders.

DOI： 10.1016/j.bone.2020.115777

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

<title>Abstract</title>Primary aldosteronism (PA) is mainly clinically classified as unilateral aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism. Immunohistochemistry for aldosterone synthase reveals a diverse PA pathology, including pathological APA and aldosterone-producing cell clusters. The relationship between PA pathology and adrenalectomy outcomes was examined herein. Data from 219 unilaterally adrenalectomized PA cases were analyzed. Pathological analyses revealed diverse putative aldosterone-producing lesions. Postoperative biochemical outcomes in 114 cases (test cohort) were classified as complete success (<italic>n</italic> = 85), partial success (<italic>n</italic> = 19), and absent success (<italic>n</italic> = 10). Outcomes in the large and small PA lesion groups, rather than between PA lesion types, were compared at five threshold values for PA lesion sizes (2–6 mm with 1-mm increments) to streamline the results. The proportion of complete success was significantly higher in the large PA lesion group than in the small PA lesion group at the 5-mm threshold only. The proportion of absent success was significantly higher in the small PA lesion group than in the large PA lesion group at all thresholds. Univariate and multivariate analyses of the test cohort identified serum K as an independent predictive factor for the small PA lesion group, which was confirmed in the 105-case validation cohort. Chi-squared automatic interaction detector analysis revealed that the best threshold of serum K for predicting large PA lesions was 2.82 mEq/L. These results will be beneficial for treating PA in clinical settings because patients with low serum K levels and apparent adrenal masses on CT may be subjected to adrenalectomy even if the adrenal venous sampling test is unavailable.

DOI： 10.1038/s41440-020-00579-w

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

<title>Abstract</title>
<sec>
<title>Context</title>
Current clinical guidelines recommend confirmation of positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results.


</sec>
<sec>
<title>Objective</title>
The aim of the present study was to explore the role of two confirmatory tests in subtype diagnosis of PA.


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<title>Design</title>
Retrospective cross-sectional study.


</sec>
<sec>
<title>Setting</title>
The study was conducted at two referral centers.


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<sec>
<title>Participants and Method</title>
We identified 360 hypertensive patients who underwent both captopril challenge test (CCT) and saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS).


</sec>
<sec>
<title>Main Outcome Measure</title>
The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests.


</sec>
<sec>
<title>Results</title>
Of patients studied, 127 were positive for both CCT and SIT (double-positive), while 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs. 72/127 [56.7%], P < 0.01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients.


</sec>
<sec>
<title>Conclusion</title>
Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.


</sec>

DOI： 10.1210/clinem/dgaa812

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context: Urinary aldosterone levels (Uald) are widely measured in the oral sodium-loading test to confirm primary aldosteronism (PA), but reliable studies on their diagnostic value are limited. This may be due to the difficulty in collecting urine with reliable accuracy, keeping oral sodium intake constant between patients. Therefore, we focused on 24-hour Uald after intravenous saline infusion in a hospitalized setting, which provides a reliable sodium load in consistent amounts. Objective: Comparing plasma aldosterone concentrations (PAC) and Uald after saline infusion in the sitting position, to evaluate the accuracy in determining PA subtypes and the correlation of both measurements. Design and Setting: This was a retrospective cross-sectional study in a single referral center. Patients: Of 53 patients without renal dysfunction who were diagnosed with PA and underwent adrenal venous sampling, 16 and 37 were diagnosed with unilateral and bilateral PA, respectively. Main Outcome Measures: Uald collected for 24 hours and PAC after saline infusion. Results: The area under the receiver operating characteristic curve for diagnosing unilateral PA was not significantly different between Uald and PAC after saline infusion (0.921 and 0.958, respectively; P = 0.370). The predicted optimal cutoff value of Uald was 16.5 μg/day (sensitivity, 87.5%; specificity, 100%), and that of PAC after saline infusion was 19.3 ng/dL (sensitivity, 87.5%; specificity, 97.3%). In studied patients with PA, Uald was positively correlated with PAC after saline infusion (r = 0.617; P < 0.001). Conclusions: We reassessed Uald in PA patients under sufficient sodium loading and demonstrated the correlation between Uald and PAC after saline infusion.

DOI： 10.1210/jendso/bvaa100

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DOI： 10.1007/s00198-020-05527-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

CONTEXT: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium. OBJECTIVE: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. DESIGN AND SETTING: A retrospective cross-sectional study in a single referral center. PARTICIPANTS: This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. MAIN OUTCOME MEASURE: Diagnostic value of PAC and serum potassium in confirmation of PA. RESULTS: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001). CONCLUSION: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.

DOI： 10.1210/clinem/dgz148

記述言語：英語   掲載種別：研究論文（学術雑誌）  

CONTEXT: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are catecholamine-producing neuroendocrine tumors, which are known to be associated with low bone mineral density (BMD). However, it remains unknown whether PPGLs are associated with high prevalence of osteoporotic fracture and if so, whether their surgical resection improves BMD has been addressed. OBJECTIVE: To evaluate the risk of vertebral fracture (VF) in PPGLs and the improvement of BMD after surgery. DESIGN AND SETTINGS: A retrospective cross-sectional study in a single referral center. PARTICIPANTS: This study included the following patients: 1) 49 patients with PPGLs and 61 patients with non-functional AT who were examined radiograph of the spine, 2) 23 patients with PPGLs who were examined BMD at follow-up. INTERVENTION: 1) The prevalence of VF was evaluated between PPGLs and non-functional AT. 2) In PPGLs, BMD was evaluated at baseline and after surgery. RESULTS: PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were associated with VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76-11.3; p = 0.001). In PPGLs, BMD at the lumber spine was improved (before: 0.855 ± 0.198 g/cm2, after: 0.888 ± 0.169 g/cm2, mean of the difference: 0.032 g/cm2, p = 0.026), with 3.8% increase. CONCLUSION: This study demonstrates that PPGLs was associated with VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis.

DOI： 10.1016/j.bone.2020.115221

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

CONTEXT: Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF. OBJECTIVE: To evaluate whether unilateral PA is associated with the prevalence of VF. DESIGN: This was a retrospective cross-sectional study in a single referral centre. PATIENTS: We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests. MEASUREMENTS: We measured the prevalence of VF, according to PA subtype. RESULTS: One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non-PA; 39 patients with PA were not subtype-classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non-PA (12%, 7/58; P = .011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P = .021). There was no significant difference in the prevalence of VF between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12-8.92; P = .017). Among patients with unilateral PA, serum cortisol concentrations after 1-mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dL) than those without (0.96 ± 0.33 g/dL; P = .048). CONCLUSIONS: Unilateral PA is an independent risk factor for VF.

DOI： 10.1111/cen.14145

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記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Primary aldosteronism (PA) is a common curable cause of hypertension. Adrenal venous sampling (AVS) is recommended for subtype diagnosis but is a difficult procedure. Recently, an increased prevalence of PA was reported, creating a greater demand for treatment of the condition in clinical facilities. The aim of the present study was to identify the historical changes over time and the differences between facilities in the success rate and subtype diagnosis of PA. The database of the PA registry developed by the Japan PA Study (JPAS) was used. A total of 2599 patients with PA who underwent AVS were evaluated. The overall success rate of AVS was 88%. The bilateral subtype was the dominant subtype, comprising 69% of cases. During the period 2004-2011 to 2011-2017, there were significant changes in the total number of AVS procedures (from 562 to 1732), ratio of ACTH administration with AVS (75 to 97%), success rate (79 to 90%), and proportion with bilateral subtype diagnosis (53 to 72%). There were also significant inter-facility differences in the number of AVS procedures (6 to 322), success rate (59 to 97%), and proportion with the bilateral subtype (44 to 86%). The principal enrolled department was Endocrinology (86%), and the ratio of unilateral PA was significantly higher in this department than in others (32% vs. 25%). In conclusion, the number of AVS procedures performed, the success rate, and the proportion with the bilateral subtype increased over time after normalizing the centre difference. Significant differences were observed between the centres.

DOI： 10.1038/s41371-019-0229-4

記述言語：日本語  

記述言語：その他  

記述言語：その他  

DOI： 10.1210/js.2019-00012

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Seated saline infusion test in predicting subtype diagnosis of primary aldosteronism.
CONTEXT: Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series. OBJECTIVE: This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT). PATIENTS AND SETTING: Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms). MAIN OUTCOME MEASURE: Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT. RESULTS: The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P = .023). ROC curve analysis predicted optimal cut-off PACs of 13.1 ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2 ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT. CONCLUSIONS: Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.

DOI： 10.1111/cen.14111

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. Design: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). Methods: We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. Results: Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. Conclusion: Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.

DOI： 10.1530/EJE-19-0047

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Because of the influence on the renin-angiotensin-aldosterone system, it is recommended to avoid, if possible, the use of angiotensin-converting-enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, β-blockers, and mineralocorticoid receptor antagonists during the diagnostic period of primary aldosteronism. A laterality index more than 4 in adrenocorticotropic hormone (ACTH)-stimulated adrenal venous sampling (ACTH-AVS) is a widely used classification of the unilateral subtype that can benefit from adrenalectomy. Here, we revealed clinical features of patients taking drugs that could affect the primary aldosteronism diagnosis (DAPD) and investigated whether the classification with laterality index more than 4 in ACTH-AVS is applicable to these patients. PATIENTS AND METHODS: Using a large database of primary aldosteronism patients in Japan, we analyzed 2122 patients with successful ACTH-AVS. RESULTS: Patients who received any DAPD (n = 209) showed higher prevalence of comorbidity burdens and took more antihypertensive drugs compared with patients without DAPD. In patients taking DAPD, those with laterality index more than 4 had a higher prevalence of hypokalemia, a higher aldosterone-to-renin ratio and a higher prevalence of adrenal mass than those with laterality index of 4 or less. Adrenalectomy was performed in 76% patients with laterality index more than 4 and 20% with laterality index of 4 or less. Patients who underwent adrenalectomy showed biochemical cure in 89% with laterality index more than 4 and 50% with laterality index of 4 or less (P = 0.001). Multivariate regression analysis showed that laterality index more than 4 was an independent predictor of a biochemical cure. Biochemical cure rate in patients with laterality index more than 4 was consistently high, irrespective of the potential effect of individual DAPD on laterality index. CONCLUSION: Our findings suggest that in primary aldosteronism patients to whom DAPD were administrated due to severe clinical features, laterality index more than 4 in ACTH-AVS could accurately predict a biochemical cure after adrenalectomy.

DOI： 10.1097/HJH.0000000000002047

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS: The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined. RESULTS: Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

DOI： 10.2337/dc18-1293

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Adrenal venous sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve the success rate of AVS, although the effects on lateralization and its outcomes in unilateral primary aldosteronism are unclear. METHODS: The success rate and lateralization indices were examined in a cohort of 2197 Japanese patients with primary aldosteronism from 28 centres who underwent AVS. Outcomes were analysed in 267 patients with aldosterone-producing adenomas (APAs). RESULTS: ACTH loading during AVS improved the success rate from 67 to 89%, while lateralization indices decreased from 62 to 28%. Bolus, bolus along with continuous infusion or continuous infusion of ACTH did not affect both indices. The absence of clinical success (i.e. unchanged or increased blood pressure) was 33% and absence of biochemical success (persistent hypokalaemia or persistently raised aldosterone-to-renin ratio, or both) was 15%. The clinical and biochemical success rates did not differ between the three groups [lateralization index >2 in basal condition (LIb) and lateralization index >4 after ACTH loading (lateralization indices), and LIb >2 + lateralization indices<4, LIb<2+lateralization indices>4]. The three groups (LIb>4+lateralization indices>4, LIb>4+lateralization indices<4 and LIb<4+lateralization indices>4) did not show any significant differences of clinical and biochemical outcome. CONCLUSION: ACTH loading during AVS improved the success rate but decreased laterality. ACTH did not affect the clinical and biochemical outcomes in APA patients. These data showed that the use of ACTH during AVS was helpful for improving the success rate, but did not contribute to better outcomes.

DOI： 10.1097/HJH.0000000000001964

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Seasonal Variation in Severe Glucose-lowering Drug-induced Hypoglycemia in Patients with Type 2 Diabetes.
Objective Glucose-lowering drug-induced hypoglycemia is a serious complication and there have been a few reports of seasonal variations in hypoglycemia in patients with type 2 diabetes. The aim of the present study was to examine the association between severe drug-induced hypoglycemia and seasonal variations, and to elucidate the contributing factors. Methods This retrospective, single center clinical study, analyzed the cases of 125 patients who required emergency hospitalization for severe drug-induced hypoglycemia between January 1, 2001 and December 31, 2014. The period from November to April was defined as the cold season. Results Severe hypoglycemia occurred more often in the cold season than in the warm season. In the cold season, 62 of 9,981 (0.6%) emergency department visits involved patients who required hospitalization for drug-induced hypoglycemia. In contrast, in the warm season, 27 of 8,649 (0.3%) visits involved patients who required hospitalization for drug-induced hypoglycemia (p=0.002). The proportion of patients treated with sulfonylurea (SU) in the cold season was higher than that in the warm season. Even the use of low-dose SU caused hypoglycemia in the cold season. In the SU-treated group, the proportion of patients with white blood cell and/or C-reactive protein elevation was higher in the cold season than in the warm season (p=0.04). Conclusion Severe glucose-lowering drug-induced hypoglycemia occured more frequently in the cold season than in the warm season, and was associated with an inflammatory state in patients treated with SU.

DOI： 10.2169/internalmedicine.1360-18

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context: Recently, the relationship between primary aldosteronism (PA) and various metabolic disorders, including obesity, diabetes mellitus, and dyslipidemia, has been discussed. However, in PA, aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) have different etiologies. Objective: Our objectives were to clarify differences in obesity and metabolic disorders between APA and IHA and to gain insight in the pathogenesis of IHA. Design, Setting, and Participants: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan Primary Aldosteronism Study. For comparative analysis, data were also collected from 274 patients with essential hypertension (EHT). Main Outcome Measures: We compared prevalences of obesity and metabolic disorders between patients with APA and patients with IHA. Comparisons with sex-, age-, and blood pressure-matched patients with EHT were also performed. Correlations between metabolic parameters and plasma aldosterone concentrations (PACs) in each subtype were analyzed. Results: Analysis of 516 patients with APA and 1015 patients with IHA revealed PACs were significantly higher in patients with APA than patients with IHA. By contrast, after we adjusted for clinical backgrounds, the prevalence of obesity was significantly higher in patients with IHA than in patients with APA or EHT. Although the prevalences of diabetes mellitus and dyslipidemia did not significantly differ between patients with IHA and patients with APA, triglyceride and HbA1c were significantly higher in patients with IHA than in patients with APA. There was no significant correlation between metabolic parameters and PACs in either subtype. Conclusions: Patients with IHA tend to be obese despite lower PACs than in patients with APA. The present results suggest that obesity-related factors contribute to the pathogenesis of IHA.

DOI： 10.1210/jc.2018-00866

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: A subtype prediction score for primary aldosteronism has not yet been developed and validated using a large dataset. This study aimed to develop and validate a new subtype prediction score and to compare it with existing scores using a large multicenter database. METHODS: In total, 1936 patients with primary aldosteronism were randomly assigned to the development and validation datasets, constituting 1290 and 646 patients, respectively. Three prediction scores were generated with or without confirmatory tests, using logistic regression analysis. In the validation dataset, new and existing prediction scores were compared using receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement analyses. RESULTS: The new prediction score is simply calculated using serum potassium levels [>3.9 mmol/l (four points); 3.5-3.9 mmol/l (three points)], the absence of adrenal nodules during computed tomography (three points), a baseline plasma aldosterone concentration of <210.0 pg/ml (two points), a baseline aldosterone/renin ratio of less than 620 (two points), and female sex (one point). Using the validation dataset, we found that a new subtype prediction score of at least 8 had a positive predictive value of 93.5% for bilateral hyperaldosteronism. The new prediction score for bilateral hyperaldosteronism was better than the existing prediction scores in the receiver operating characteristic curve and net reclassification improvement analyses. CONCLUSION: The new prediction score has clear advantages over the existing prediction scores in terms of diagnostic accuracy, feasibility, and the potential for generalization in a large population. These data will help healthcare professionals to better select patients who require adrenal venous sampling.

DOI： 10.1097/HJH.0000000000001855

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context: Primary aldosteronism (PA) in the elderly has increased in importance in association with population aging. Objective: To investigate the characteristics and outcomes of elderly patients with PA undergoing adrenalectomy. Patients and Methods: Using a database of patients with PA who underwent adrenal venous sampling (AVS), we compared elderly patients (≥65 years old) with nonelderly patients (<65 years old) in terms of characteristics, subtype classification in ACTH-stimulated AVS, and outcomes after adrenalectomy. Results: The elderly group had a higher prevalence of comorbidities than the nonelderly group. The proportion of the unilateral subtype [defined as a lateralization index (LI) >4] was comparable between the age groups. In patients who received adrenalectomy, biochemical cure was comparable between the groups, whereas persistent hypertension was more common in the elderly group. The prevalences of hyperkalemia and renal impairment (chronic kidney disease stage 3b or higher) were higher in the elderly group. Multiple regression analysis showed that the duration of hypertension predicted persistent hypertension and hyperkalemia and that preoperative estimated glomerular filtration rate predicted renal impairment in the elderly group. LI >4 in AVS was an independent predictor of biochemical cure after adrenalectomy in the elderly group but not in the nonelderly group. Age was negatively associated with biochemical cure in patients with LI ≤4. Conclusion: Adrenalectomy contributes to biochemical improvement in elderly patients if determined in accordance with AVS. The treatment strategy should be determined considering the high postoperative incidence of persistent hypertension and hyperkalemia in elderly patients with a long history of hypertension or renal impairment in those with reduced renal function.

DOI： 10.1210/jc.2018-00059

記述言語：英語  

Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], P<0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], P<0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; P<0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; P=0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.

DOI： 10.1161/HYPERTENSIONAHA.118.11382

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: The aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes. Patients and Methods: Cosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery. Main Outcome Measures: The proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined. Results: Clinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 (P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 (P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55). Conclusions: Difference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA.

DOI： 10.1210/js.2018-00055

記述言語：英語   掲載種別：研究論文（学術雑誌）  

CONTEXT: The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature. OBJECTIVE: We sought to determine the accuracy of CT findings in young PA patients who had unilateral adrenal disease on CT with hypokalaemia and elevation of aldosterone. DESIGN AND PATIENTS: We retrospectively studied 358 PA patients (n = 30, aged <35 years; n = 39, aged 35-40 years; n = 289, aged ≥40 years) with hypokalaemia and elevation of aldosterone and unilateral disease on CT who had successful AVS. MAIN OUTCOME MEASURE: Accuracy of CT findings is determined by AVS findings and/or surgical outcomes in patients aged <35 years. RESULTS: Concordance of the diagnosis between CT and AVS was 90% (27/30) in patients aged <35 years, 79% (31/39) in patients aged 35-40 years and 69% (198/289) in those aged ≥40 years (trend for P < .01). Surgical benefit was confirmed in three patients aged <35 years and in three patients aged 35-40 years with the available surgical data who had discordance between CT and AVS findings. Collectively, the diagnostic accuracy of CT findings was 100% (30/30) if aged <35 years and 87% (34/39) if aged 35-40 years. CONCLUSION: Primary aldosteronism patients aged <35 years with hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT could be spared AVS.

DOI： 10.1111/cen.13582

記述言語：その他  

The Occurrence of Apparent Bilateral Aldosterone Suppression in Adrenal Vein Sampling for Primary Aldosteronism.

DOI： 10.1210/js.2017-00481

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context: The number of centers with established adrenal venous sampling (AVS) programs for the subtype diagnosis of primary aldosteronism (PA) is limited. Objective: Aim was to develop an algorithm for AVS based on subtype prediction by computed tomography (CT) and serum potassium. Design: A multi-institutional retrospective cohort study in Japan. Patients: A total of 1591 patients with PA were classified into four groups according to CT findings and potassium status. Subtype diagnosis of PA was determined by AVS. Main Outcome Measure: Prediction value of the combination of CT findings and potassium status for subtype diagnosis. Results: The percentages of unilateral hyperaldosteronism on AVS were higher in patients with unilateral disease on CT than those with bilateral normal results on CT (50.8% vs 14.6%, P < 0.01), and these percentages were higher in those with hypokalemia than those with normokalemia (58.4% vs 11.5%, P < 0.01). The prevalence and odds ratio for unilateral hyperaldosteronism on AVS were as follows: bilateral normal on CT with normokalemia, 6.2% (reference); unilateral disease on CT with normokalemia, 23.8% and 4.8 [95% confidence interval (CI), 3.1 to 7.2]; bilateral normal on CT with hypokalemia, 38.1% and 9.4 (95% CI, 6.2 to 14.1), and unilateral disease on CT with hypokalemia, 70.6% and 36.4 (95% CI, 24.7 to 53.5). Conclusions: Patients with PA with bilateral normal results on CT and normokalemia likely have a low prior probability of a lateralized form of AVS and could be treated medically, whereas those with unilateral disease on CT and hypokalemia have a high probability of a lateralized form of AVS.

DOI： 10.1210/jc.2017-01774

記述言語：英語   掲載種別：研究論文（学術雑誌）  

There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K+ ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with PA seem to be at a higher risk of developing CVD than patients with essential hypertension. Moreover, patients with PA presenting with hypokalemia, the unilateral subtype, or plasma aldosterone concentration ≥125 pg/mL are at a greater risk of CVD and have a greater need for PA-specific treatments than others.

DOI： 10.1161/HYPERTENSIONAHA.117.10263

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Subtype diagnosis of primary aldosteronism (PA) by adrenal vein sampling (AVS) is recommended as a mandatory step for indicating adrenal surgery. It is a technically demanding procedure, especially in the right adrenal vein. The aim of the study was to predict the subtype diagnosis in the absence of values from the right AVS. From the databases of nine centers (WAVES-J), 308 patients with PA who underwent successful AVS were studied. Based on the ipsilateral ratio (IR) (aldosterone/cortisol ratio of the left adrenal vein [A/Cleft AV] / aldosterone/cortisol ratio of the inferior vena cava [A/CIVC]), the patients were divided into two groups: the patients with IR ≥ 1.0 (n = 262) and those with IR &lt
1.0 (n = 46). In patients with IR &gt
1.0, the A/Cleft AV was significantly higher in patients with the left unilateral subtype than in patients with the bilateral subtype. Receiver operating characteristic (ROC) curve analysis revealed that an A/Cleft AV cutoff &gt
68 showed 70.8% sensitivity and 93.5% specificity for the left unilateral subtype. On the other hand, in patients with IR &lt
1.0, the A/Cleft AV was significantly lower in patients with the right unilateral subtype. ROC analysis revealed that an A/Cleft AV cutoff &lt
9 showed 86.7% sensitivity and 75.0% specificity for the right unilateral subtype. Hence, the combination of the IR and A/C ratio in the left adrenal vein is useful for predicting the subtype. The present results provide important information for patients with PA in whom AVS was unsuccessful in the right adrenal vein.

DOI： 10.1038/s41371-017-0015-0

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Differentiation of unilateral from bilateral aldosterone hypersecretion is the essential step in the clinical practice of primary aldosteronism (PA). Although adrenal venous sampling (AVS) has been established as the most standard test recommended by the guideline, its invasive and technically difficult nature has facilitated the approach to develop non-invasive functioning imaging as an alternative test. Compared to the conventional adrenocortical scintigraphy with cholesterol derivatives as tracer, the first-generation imaging, both of (11) C-MTO/PET and (123) I-IMTO/SPECT/CT, the second-generation imaging, bind with high specificity and affinity to CYP11B enzymes and have advantages in shortening the time for obtaining specific images, reducing the radiation exposure to the patient, and resolution of the images. Because of very short half-life of (11) C-MTO, (123) I-IMTO has a potential for a wider application than (11) C-MTO. Sensitivity of identifying an adenoma smaller than 1cm in diameter is still a common limitation of these new functional imaging methods. The new functional imaging could be supplementary to AVS in lateralization of PA when the results of AVS are not conclusive. To be a substitute for AVS, however, it should fulfill various conditions including high selectivity and binding affinity to CYP11B2, high sensitivity in detecting small adenoma, high resolution image, reduction of radiation exposure, and general versatility. Considering the potential number of patients, cost-effectiveness of the subtype testing in the clinical practice of PA could be one of the issues of the medical expenses. Thus, development of a new non-invasive functional imaging will have a significant impact on the clinical practice of PA and hypertension.

DOI： 10.1055/s-0043-120672

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hyperkalemia is an important complication of adrenalectomy for patients with primary aldosteronism (PA). The frequency of hyperkalemia after medication using mineralocorticoid receptor antagonists (MRAs) for PA is unclear. The aim of this study is to investigate the frequency and the risk factors of hyperkalemia after surgery and medication for PA. The data of 376 patients with PA registered in a multicentre-collaborative study in Japan, including surgically treated patients (group A; n = 142) and medically treated patients with MRAs (group B; n = 234) were studied. The prevalence of hyperkalemic patients (serum potassium > 5.0 mEq l(-1)) after treatment was higher in group A than group B (9.9 vs 3.8%, P < 0.01). At diagnosis, the hyperkalemic patients were older and had a poorer renal function than the non-hyperkalemic patients in both groups (P < 0.05). The hyperkalemic patients had severer PA in group A and milder PA in group B. The independent risk factor by a logistic regression analysis was only age in both groups. After treatment, the percentages of patients withdrawing antihypertensive drugs and the normalization of aldosterone renin ratio were not different between hyperkalemic and non-hyperkalemic patients in group A. The type and dose of MRAs and the combination of other antihypertensive drugs were not different between hyperkalemic and non-hyperkalemic patients in group B. In conclusion, the potential occurrence of hyperkalemia should be considered after medical as well as surgical treatment for PA, especially in patients with older age (> 60 years) and impaired renal function (estimated glomerular filtration rate < 70 ml min(-1) per 1.73 m(2)) at diagnosis.

DOI： 10.1038/jhh.2017.38

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome.
Methods The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes.
Findings Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a wide variance (range 17-62), and partial clinical success in an additional 334 (47%, range 35-66); complete biochemical success was seen in 656 (94%, 83-100) of 699 patients. Female patients had a higher likelihood of complete clinical success (odds ratio [OR] 2.25, 95% CI 1.40-3.62; p=0.001) and clinical benefit (complete plus partial clinical success; OR 2.89, 1.49-5.59; p=0.002) than male patients. Younger patients had a higher likelihood of complete clinical success (OR 0.95 per extra year, 0.93-0.98; p<0.001) and clinical benefit (OR 0.95 per extra year, 0.92-0.98; p=0.004). Higher levels of preoperative medication were associated with lower levels of complete clinical success (OR 0.80 per unit increase, 0.70-0.90; p<0.001).
Interpretation These standardised outcome criteria are relevant for the assessment of the success of surgical treatment in individual patients and will allow the comparison of outcome data in future studies. The variable baseline clinical characteristics of our international cohort contributed to wide variation in clinical outcomes. Most patients derive clinical benefit from adrenalectomy, with younger patients and female patients more likely to have a favourable surgical outcome. Screening for primary aldosteronism should nonetheless be done in every individual fulfilling US Endocrine Society guideline criteria because biochemical success without clinical success is by itself clinically important and older women and men can also derive post-operative clinical benefit.

DOI： 10.1016/S2213-8587(17)30135-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although laterality assessed by computed tomography (CT) in primary aldosteronism (PA) is not always concordant with that assessed by adrenal vein sampling (AVS), it is unclear whether all patients diagnosed with PA should undergo AVS for subtype classification. The aim of the current study was to investigate the accuracy of CT in subtype classification and to develop a prediction score for bilateral subtype in patients without adrenal tumour. As part of the WAVES-J study, 393 patients with PA were analysed. Subtyping using CT was concordant with that using AVS in 68% (269/393) of patients in the total sample, and in 38% (68/156) of patients with unilateral tumours, 56% (5/9) of patients with bilateral tumours and 89% (204/228) of patients without tumour. In patients without tumour, female gender, plasma aldosterone concentration (pg ml(-1)) to plasma renin activity ratio. 550 and serum potassium. 3.8 mEq l (-1) were shown to be independent predictors for bilateral subtype. A prediction score based on these three variables was constructed with one point attributed to each variable. A score of three points had 29% sensitivity and 96% specificity in a receiver operating characteristic curve analysis. The results suggest that although CT is not sufficiently accurate for subtype classification in patients with adrenal tumours, it is sufficient to determine bilateral subtype in patients without tumour. Moreover, using our clinical prediction score in patients without tumour could be useful in determining the necessity of AVS for subtype classification.

DOI： 10.1038/jhh.2016.61

記述言語：英語   掲載種別：研究論文（学術雑誌）  

ObjectiveAlthough corticotropin is a representative secretagogue of aldosterone, the utility of the cosyntropin stimulation test (C-ST) in diagnosing primary aldosteronism (PA) has not been elucidated. Aim of the study was to evaluate the clinical utility of C-ST for confirmatory testing and subtype classification of PA.
Design, Setting and PatientsIn this retrospective study, we identified patients with hypertension and positive case-detection results for PA who underwent C-ST and saline infusion testing (SIT) between 2006 and 2013 at eight referral centres in Japan. PA and essential hypertension (EH) were distinguished based on SIT results. PA subtype classification was determined by adrenal venous sampling (AVS). Plasma aldosterone concentration (PAC) was measured before and 30 and 60 min after intravenous cosyntropin administration. The ability of C-ST to distinguish PA from EH and to distinguish unilateral from bilateral disease was assessed by the area under the receiver operating characteristic curve.
ResultsOf 205 patients with hypertension and positive case-detection results, 139 (68%) had PA based on SIT results. Eighteen patients in whom AVS was unsuccessful were excluded from analysis. The baseline PAC before C-ST was significantly higher (P < 001) in patients with PA than in those with EH. However, the degree of difference in PAC between patients with PA and EH was not enhanced by the administration of cosyntropin. In addition, the administration of cosyntropin did not improve the distinction between bilateral and unilateral PA subtypes.
ConclusionsC-ST has no utility as a confirmatory and subtype testing of PA when the diagnosis of PA is based on the positive results in SIT.

DOI： 10.1111/cen.13167

記述言語：英語   掲載種別：研究論文（学術雑誌）  

ContextIn adrenal vein sampling (AVS) for patients with primary aldosteronism, the contralateral ratio of aldosterone/cortisol (A/C) between the nondominant adrenal vein and the inferior vena cava is one of the best criteria for determining lateralized aldosterone secretion. Despite successful cannulation in some patients, the A/C ratios in the adrenal veins are bilaterally lower than that in the inferior vena cava (bilateral aldosterone suppression; BAS).
ObjectivesTo investigate the prevalence of BAS in AVS and how to resolve this condition.
Design and settingRetrospective study involving nine referral centres.
PatientsFour hundred and ninety-one patients who were confirmed as having primary aldosteronism and had an AVS between January 2006 and December 2013.
MeasurementsThe prevalence of BAS before and after ACTH stimulation was compared. In addition, we investigated other methods for overcoming BAS.
ResultsIn 304 patients with successful AVS before ACTH stimulation, BAS was observed in 29 (95%). BAS was resolved after ACTH stimulation in 22 patients. In 276 patients with successful AVS both before and after ACTH stimulation, the frequency of BAS was significantly reduced after ACTH (87% vs 25%, P < 001). In a few patients, BAS was also resolved by adding a sampling point at the common trunk of the left adrenal vein and by an alternative drainage vein from the adrenal tumour.
ConclusionsBAS sometimes occurs in AVS without ACTH stimulation. ACTH stimulation significantly reduces BAS with a single AVS procedure.

DOI： 10.1111/cen.13090

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154-69 920) in the higher side and 12 953 (range, 1866-36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4-66.0] versus 17.3 [4.0-59.0] pg/mL per mu g/dL; P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index >= 4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA.

DOI： 10.1161/HYPERTENSIONAHA.115.06607

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Context Although adrenal vein sampling (AVS) is the standard method for subtype diagnosis in primary aldosteronism (PA), protocol details including the sampling position in the adrenal vein are not standardized.
Objective To establish the optimum sampling position in the left adrenal vein based on postoperative outcome in PA patients.
Design and Setting Retrospective study in nine referral centres.
Participants Of 496 consecutive PA patients who underwent AVS between 2006 and 2013, 217 with successful AVS under cosyntropin stimulation, and with concomitant data from two positions: proximal (common trunk) and distal (central vein) to the junction with the inferior phrenic vein, were included.
Main outcome measures Discordant rate of subtype diagnosis between common trunk and central vein, and postoperative outcomes in patients with discordant results.
Results Subtype diagnosis using common trunk and central vein was discordant in 10 (4.6%) of the 217 patients (kappa = 0.87, P < 0.05). Of these 10 patients, eight with left unilateral subtype and two with bilateral subtype using common trunk data showed bilateral subtype and unilateral subtype, respectively, using central vein data. Five patients with left unilateral subtype and one with bilateral subtype by common trunk data underwent unilateral adrenalectomy. All six patients were cured of PA after adrenalectomy, resulting in false-negative rates of 17% (1/6) by common trunk data, and 83% (5/6) by central vein data.
Conclusion In view of its better potential diagnostic accuracy, technical ease, lower cost and lower risk of vein rupture, blood sampling from the common trunk of the left adrenal vein may be preferable as the standard method of AVS in patients with PA, although additional studies in a larger number of cases are required.

DOI： 10.1111/cen.12847

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12020-015-0615-9

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives Adrenal vein sampling (AVS) is the standard criterion for the subtype diagnosis in primary aldosteronism (PA). Although lateralized index (LI) >= 4 after cosyntropin stimulation is the commonly recommended cut-off for unilateral aldosterone hypersecretion, many of the referral centres in the world use LI cut-off of <4 without sufficient evidence for its diagnostic accuracy.
Aim The aim of the study was to establish the diagnostic significance of contralateral (CL) aldosterone suppression for the subtype diagnosis in patients with LI <4 in AVS.
Design and patients A retrospective multicentre study was conducted in Japan. Of 124 PA patients subjected to unilateral adrenalectomy after successful AVS with cosyntropin administration, 29 patients with LI < 4 were included in the study. The patients were divided into Group A with CL suppression (n = 16) and Group B (n = 13) without CL suppression. Three outcome indices were assessed after 6 months postoperatively: normalization/significant improvement of hypertension, normalization of the aldosterone to renin ratio (ARR) and normalization of hypokalaemia.
Results The normalization/significant improvement of hypertension was 81% in Group A and 54% in Group B (P = 0.2). The normalization of ARR was 100% in Group A and 46% in Group B (P = 0.004). Hypokalaemia was normalized in all patients of both groups. The overall cure rate of PA based on meeting all the three criteria was 81% in Group A and 31% in Group B (P = 0.01).
Conclusions In patients with PA, where the LI is < 4 on AVS, CL suppression of aldosterone is an accurate predictor of a unilateral source of aldosterone excess. CL suppression data should be interpreted in conjunction with computed tomographic adrenal imaging findings to guide surgical management.

DOI： 10.1111/cen.12761

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

ContextChronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation.
ObjectiveOur study aim was to elucidate factors responsible for developing postoperative CKD and to provide a simple scoring system to predict postoperative CKD in PA.
Design and PatientsForty-five patients with PA treated with unilateral adrenalectomy and followed for at least 1month postsurgery were studied. Thirty-one patients with non-PA adrenal disease who underwent unilateral adrenalectomy were also studied as control. Patients with pre-operative estimated glomerular filtration rate (eGFR)<60ml/min/173 m(2) were excluded from both groups.
ResultsA statistically significant (P<0001) decrease in eGFR was observed in PA group within 1month of surgery, then stabilized. Of the 45 patients with PA, 17 (378%) developed CKD after surgery. None of the non-PA group developed CKD after surgery. Of the pre-operative variables, logistic regression analysis showed that lower eGFR and higher aldosterone-to-renin ratios (ARR) were the independent predictors for postoperative CKD in PA. Optimal cut-off values of the two variables analysed with ROC curves were as follows: eGFR769ml/min/173m(2) and ARR305. Using these data, we created a CKD score as a tool for predicting postoperative CKD, with an AUC for the score of 08866.
ConclusionThe pre-operative eGFR and ARR were the significant contributing factors for postoperative CKD in PA. By combining these independent factors, we created a CKD score which provides useful information before surgery about the risk for development of postoperative CKD.

DOI： 10.1111/cen.12497

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記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞Point　●原発性アルドステロン症とCushing症候群の診断は,それぞれアルドステロン産生とコルチゾール産生の調節メカニズムを利用する内分泌検査所見に基づく.●アルドステロンとコルチゾールの産生病変の病理診断には,それぞれの合成経路に特異的な酵素であるCYP11B2とCYP11B1の免疫組織化学的検出が行われる.●アルドステロンの過剰産生細胞には,KCNJ5遺伝子変異などの細胞内カルシウム濃度上昇をきたす遺伝子変異が知られる.●コルチゾールの過剰産生細胞には,PRKACA遺伝子変異などの細胞内サイクリックAMPの濃度上昇をきたす遺伝子変異が知られる.

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語  

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記述言語：その他  

記述言語：日本語  

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記述言語：日本語  

記述言語：英語  

The Delayed Diagnosis of Thyroid Storm in Patients with Psychosis.
We herein report two cases of patients with thyroid storm with a delayed diagnosis due to psychosis. The patients were a 63-year-old woman with bipolar II disorder and a 37-year-old man with major depressive disorder. The psychoses in both patients were well controlled with medication. Although they both showed symptoms of thyrotoxicosis, the symptoms were ignored, presumably because the psychological manifestations of worsening of psychosis and thyroid storm are similar. When the mental or physical state of patients with psychosis changes, thyroid hormone levels should be measured for early treatment.

DOI： 10.2169/internalmedicine.2681-19

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

褐色細胞腫・パラガングリオーマの診断と治療 Up-to-Date

記述言語：日本語  

原発性アルドステロン症 診断・治療の最前線 原発性アルドステロン症の診療水準の向上 コンセンサス・ステートメントとAMED-Japan PA Study(JPAS)による新規エビデンス

記述言語：日本語  

腫瘍細胞性と粘液性の特徴を有する副腎皮質腫瘍の1症例(A case of adrenocortical tumor with oncocytic and myxoid feature)

記述言語：日本語  

6年間の経過で病型診断が変化した原発性アルドステロン症の1例

記述言語：日本語  

6年間の経過で病型診断が変化した原発性アルドステロン症の1例

記述言語：日本語  

TRAb値とTSAb値に乖離を認めた高齢男性の甲状腺眼症の1例

記述言語：日本語  

ミネラルコルチコイド受容体拮抗薬(MRA)使用下での副腎静脈サンプリング(AVS)の局在診断精度の検討

記述言語：日本語  

原発性アルドステロン症の手術/薬物治療における重症度分類の検証

記述言語：日本語  

原発性アルドステロン症における副腎静脈サンプリングの適応と判定基準の標準化

記述言語：日本語  

多施設共同研究による原発性アルドステロン症の副腎静脈サンプリングにおける新たなエビデンスの創出

記述言語：日本語  

当院における原発性アルドステロン症(PA)患者への手術加療による治療アウトカム

記述言語：日本語  

肝腫瘍との鑑別を要した副腎皮質癌の一例

記述言語：日本語  

「ミネラルコルチコイド受容体と心血管疾患」 副腎静脈サンプリングの適応の精緻化 局在診断と術後アウトカムの観点から

記述言語：日本語  

原発性アルドステロン症(PA)は高血圧における頻度が高く、治癒可能である一方、適切な診断・治療の遅れは治療抵抗性高血圧、種々の標的臓器障害の原因となることから、診療水準の向上と標準的医療の普及は重要な臨床的課題である。日本内分泌学会は日本高血圧学会、日本内分泌外科学会と協力して、診療の主要なクリニカルクエッションに対するクリニカルアンサーを、客観的なエビデンスに基づいたステートメントとして発表した。要点は(1)PA高頻度の高血圧患者での積極的なスクリーニング実施、(2)ARR>200とPAC>120pg/mlの場合にスクリーニング陽性と判断、(3)機能確認検査:カプトプリル試験、生食負荷試験、フロセミド立位試験、経口食塩負荷試験の中から少なくとも1種類の陽性を確認、(4)副腎腫瘍の確認のためthin sliceでの副腎SDCTを実施、(5)手術適応を考慮する場合は原則AVSを実施。ただし、35歳以下の典型的PAではAVSの省略も考慮、(6)局在判定の指標:ACTH負荷後Lateralized ratio(LR)>4かつContralateral ratio(CR)>1を推奨。結果が乖離した場合は総合判定、(7)片側性病変では副腎摘出術、両側性病変や手術不能な場合はMR拮抗薬を第一選択とする薬物治療、などである。しかしながら、わが国独自のエビデンスは不十分で、今後、現在進行中のAMED難治性疾患実用化研究JPASの結果を踏まえた改訂が必要と考えられる。(著者抄録)

記述言語：日本語  

原発性アルドステロン症における副腎静脈サンプリング適応の精緻化 CTと血清カリウムを用いた分類

記述言語：日本語  

原発性アルドステロン症、サブクリニカルクッシング症候群を合併したAdrenocortical oncocytomaの一例

記述言語：日本語  

原発性アルドステロン症の病型診断におけるCTと血清カリウムの意義

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原発性アルドステロン症手術治療例における重症度の経時的変化

記述言語：日本語  

片側性原発性アルドステロン症(UPA)の心血管・腎疾患転帰 手術と薬物治療の比較研究

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原発性アルドステロン症の病型診断におけるCTの意義の再評価

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原発性アルドステロン症のスクリーニングにアルドステロン濃度を付加する臨床的意義

記述言語：日本語  

原発性アルドステロン症の副腎静脈サンプリングにおけるBilateral Aldosterone Suppression(BAS)に関する検討(WAVES-J study)

記述言語：日本語  

記述言語：日本語  

New treatment of malignant pheochromocytoma/paraganglioma

記述言語：日本語  

若年者原発性アルドステロン症の局在診断におけるCT所見の意義

記述言語：日本語  

PAにおけるPAC≦120pg/ml症例の検討

記述言語：日本語  

原発性アルドステロン症診断におけるACTH負荷試験の意義

記述言語：日本語  

原発性アルドステロン症の機能確認と病型診断予測におけるACTH負荷試験の意義

記述言語：日本語  

原発性アルドステロン症確定診断の予測因子としての診断時のアルドステロン/レニン比とアルドステロン濃度の意義 WAVES-J研究より

記述言語：日本語  

原発性アルドステロン症の外科的治療と内科的治療の選択

記述言語：日本語  

原発性アルドステロン症(PA)の副腎静脈サンプリング(AVS)による病型診断の再現性に関する検討

記述言語：日本語  

新規遺伝子変異を認めた褐色細胞腫・傍神経節腫症候群の男児の一例

記述言語：日本語  

若年者原発性アルドステロン症の局在診断におけるCT所見の意義

記述言語：日本語  

診断・治療に苦労した副腎腫瘍 臨床と病理から 肝腫瘍との鑑別を要した副腎皮質癌の一例

記述言語：日本語  

非原発性アルドステロン症における副腎静脈血中アルドステロンの動態

記述言語：日本語  

若年者原発性アルドステロン症の局在診断におけるCT所見の意義

記述言語：日本語  

原発性アルドステロン症の病型診断において副腎静脈サンプリング(AVS)は標準的な診断法とされるが、AVSの判定基準や実施方法は標準化されておらず、その診断精度は十分に担保されていない。そのためわれわれはAVSに関するエビデンスを創出のためのAVSデータベース(WAVES-J)を構築し、1)AVSの成功率、2)左副腎静脈採血部位、3)局在判定基準に関する知見を得た。成功率についてはAVSに熟練した施設では約90&#37;の成功率が得られ熟練施設への集約化の必要性が示唆された。採血部位については、左副腎静脈の中心静脈と下横隔静脈との合流部である共通幹での採血が費用、容易さ、診断精度の点からも標準的であると考えられた。局在判定基準については、AVSの結果が"グレーゾーン"の症例では対側副腎の抑制を示すContralateral ratioが手術適応の決定に重要であること示された。今後さらにAVSの標準化に関するエビデンスの確立が期待される。(著者抄録)

DOI： 10.11226/jaesjsts.32.4_220

記述言語：日本語  

若年者原発性アルドステロン症の局在診断におけるCT所見の意義

記述言語：日本語  

PA局在診断におけるAVSの左副腎静脈採血部位の意義

記述言語：日本語  

副腎静脈サンプリングにおける左副腎静脈採血部位が原発性アルドステロン症の局在診断に及ぼす影響 WAVES-J研究における解析

記述言語：日本語  

原発性アルドステロン症におけるCT画像による病側診断率および副腎静脈サンプリングの適応に関する検討 WAVES-J研究より

記述言語：日本語  

原発性アルドステロン症の病型予測スコア WAVES-J研究による検証

記述言語：日本語  

若年者原発性アルドステロン症の局在診断におけるCT所見の意義

記述言語：日本語  

実施診療における原発性アルドステロン症の診断

記述言語：日本語  

副腎静脈サンプリングにおける左副腎静脈採血部位が原発性アルドステロン症の局在診断に及ぼす影響 WAVES-J研究における解析

記述言語：日本語  

原発性アルドステロン症の局在診断における副腎静脈サンプリングの判定基準 Contralateral ratio(CR)の診断的意義

記述言語：日本語  

Prognosis and QOL of pheochromocytoma/paraganglioma

記述言語：日本語  

Paroxysmal hypertension

記述言語：日本語  

Pheochromocytoma : Points of informed concent for patients

記述言語：英語  

記述言語：英語  

記述言語：日本語  

当院健康管理センターを受診し、上腕-足首間脈波伝搬速度(baPWV)を測定した1,240名(PWV群)と頸動脈内膜中膜厚(IMT)を計測した2044名(IMT群)を対象にし、動脈硬化危険因子がIMTおよびPWVに及ぼす影響を単相関分析と重回帰分析により検討した。単相関分析では、IMTはすべての動脈硬化危険因子(年齢、BMI、血圧、空腹時血糖値、中性脂肪値、LDLコレステロール値、HDLコレステロール値)と有意な相関を認めたが(HDLコレステロール値とは負の相関、それ以外とは正の相関)、PWVはBMIとLDLコレステロール値とは有意な相関を認めなかった。重回帰分析では、収縮期血圧はIMTよりPWVへの影響がより大きかった。また、HDLコレステロールはIMT、PWV両者に対し有意に逆の影響を与える危険因子であったが、LDL-Cは両者に有意な影響を与えていなかった。さらに、BMIはIMTを増加させるように有意に影響していたが、逆にPWVに対しては減少させるように有意に影響していた。健診受診者においては、それぞれの動脈硬化危険因子がIMTとPWVに及ぼす影響は異なり、またBMIはbaPWVと逆相関する可能性が示唆された。さらに、HDLコレステロール管理の重要性が示唆された。(著者抄録)

記述言語：日本語  

Hypertension associated with pheochromocytoma : Pathophysiology and treatment

記述言語：日本語  

Present state and problems of genetic testing in pheochromocytoma