Article
Endocrinology & Metabolism
Kazuki Nakai, Katsunori Manaka, Junichiro Sato, Maki Takeuchi, Yuto Yamazaki, Hironobu Sasano, Yuya Tsurutani, Jun Saito, Tetsuo Nishikawa, Taroh Ri, Masaomi Nangaku, Noriko Makita
Summary: This study investigates the association between the size and aldosterone-producing ability of aldosterone-producing adenomas. The results suggest that larger tumors have higher aldosterone-producing ability, and there are differences in pathology and gene mutations.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Kang-Yung Peng, Hung-Wei Liao, Jeff S. Chueh, Chien-Yuan Pan, Yen-Hung Lin, Yung-Ming Chen, Peng-Ying Chen, Chun-Lin Huang, Vin-Cent Wu
Summary: Mutated KCNJ5 channel plays a crucial role in the pathogenesis of aldosterone-producing adenoma, disrupting potassium ion selectivity and increasing autonomous aldosterone production. Immunohistochemical and patch-clamp experiments confirmed the functional properties of the mutation, while macrolide antibiotics were ineffective in interfering with the aberrant electrophysiological properties induced by the mutation.
Article
Peripheral Vascular Disease
Yuhong Yang, Martina Tetti, Twinkle Vohra, Christian Adolf, Jochen Seissler, Michael Hristov, Alexia Belavgeni, Martin Bidlingmaier, Andreas Linkermann, Paolo Mulatero, Felix Beuschlein, Martin Reincke, Tracy Ann Williams
Summary: APAs exhibit transcriptome differences of different sizes, with BEX1 showing higher expression in micro-APAs compared to macro-APAs, negatively correlated with APA diameter, and promoting cell survival by regulating ferroptosis.
Article
Endocrinology & Metabolism
Liling Zhao, Jinjing Wan, Yujun Wang, Wenjun Yang, Qi Liang, Jinrong Wang, Ping Jin
Summary: This study presents a rare case of co-existing Cushing's syndrome and primary aldosteronism caused by bilateral adrenocortical adenomas secreting aldosterone and cortisol. Through clinical examinations and pathological analysis, it was found that the heterogeneity of tumor cell compositions and a mutation in the KCNJ5 gene may have led to different hormone secretions in the bilateral adrenal adenomas.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Endocrinology & Metabolism
Kazutaka Nanba, William E. Rainey
Summary: Primary aldosteronism is a common cause of secondary hypertension, and recent studies have revealed that most aldosterone-producing adenomas harbor somatic mutations in aldosterone-driver genes. These mutations alter intracellular ion homeostasis and enhance aldosterone production, with evidence suggesting that race and sex impact the somatic mutation spectrum of APA.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shogo Harashima, Yuto Yamazaki, Naoki Motomura, Yoshikiyo Ono, Kei Omata, Yuta Tezuka, Ryo Morimoto, Yasuhiro Nakamura, Fumitoshi Satoh, Hiroyoshi Suzuki, Go Eun Kwon, Man Ho Choi, Hironobu Sasano
Summary: This study analyzed the histological characteristics, cholesterol metabolism, and differences related to gene mutations in aldosterone-producing adenomas (APAs). The results showed that mutated KCNJ5 genes in APAs were associated with higher plasma aldosterone concentration and more lipid droplets in compact tumor cells compared to non-mutated APAs. Additionally, cholesterol uptake and synthesis were found to be different between clear and compact tumor cells, with mutated KCNJ5 APAs showing enhanced cholesterol ester uptake and de novo synthesis.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jacopo Pieroni, Yuto Yamazaki, Xin Gao, Yuta Tezuka, Hiroko Ogata, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Yasuhiro Nakamura, Fumitoshi Satoh, Hironobu Sasano
Summary: The study revealed that in aldosterone-producing adenomas and idiopathic hyperaldosteronism, cells in the zona glomerulosa exhibited significantly higher levels of senescence compared to other regions. Additionally, laboratory findings of primary aldosteronism were significantly correlated with specific gene mutations.
Review
Biochemistry & Molecular Biology
Takumi Kitamoto, Tetsuo Nishikawa
Summary: Hypertension caused by primary aldosteronism poses a greater risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation and the presence of CYP11B2-positive aldosterone-producing micronodules have significantly advanced our understanding of the pathogenesis of primary aldosteronism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Linghui Kong, Jin Zhang, Lei Dong, Jianzhong Xu, Ping-Jin Gao, Ji-Guang Wang, Limin Zhu
Summary: This case report describes a 29-year-old female patient who underwent complete adrenalectomy for left aldosterone-producing adenoma in 2004 and partial right adrenalectomy for recurrent primary aldosteronism in 2018. Sanger sequencing revealed that both left and right adenomas carried the same aldosterone-driver KCNJ5 gene mutation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Yi-Ju Chen, Kang-Yung Peng, Jeff S. Chueh, Hung-Wei Liao, Tsung-Yi Hsieh, Vin-Cent Wu, Shuo-Meng Wang
Summary: This study reported a PA patient with concomitant ACS, showing that bilateral APM may coexist with histopathologically classical and non-classical PA adenomas with different somatic mutations.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Peripheral Vascular Disease
Shinji Kishimoto, Kenji Oki, Tatsuya Maruhashi, Masato Kajikawa, Aya Mizobuchi, Takahiro Harada, Takayuki Yamaji, Yu Hashimoto, Kenichi Yoshimura, Yukiko Nakano, Chikara Goto, Farina Mohamad Yusoff, Ayumu Nakashima, Yukihito Higashi
Summary: This study aimed to evaluate the effects of KCNJ5 mutation on vascular function and vascular structure in aldosterone-producing adenoma (APA) and the effects of adrenalectomy on these factors in APA patients with and without KCNJ5 mutation. The study found that APA patients had lower flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) compared to patients with essential hypertension (EHT). After adrenalectomy, FMD and NID significantly improved in APA patients with KCNJ5 mutation, while only NID improved in APA patients without KCNJ5 mutation.
HYPERTENSION RESEARCH
(2023)
Article
Genetics & Heredity
Junhua Zhou, Elena A. B. Azizan, Claudia P. Cabrera, Fabio L. Fernandes-Rosa, Sheerazed Boulkroun, Giulia Argentesi, Emily Cottrell, Laurence Amar, Xilin Wu, Sam O'Toole, Emily Goodchild, Alison Marker, Russell Senanayake, Sumedha Garg, Tobias Akerstrom, Samuel Backman, Suzanne Jordan, Satyamaanasa Polubothu, Daniel M. Berney, Anna Gluck, Kate E. Lines, Rajesh V. Thakker, Antoinette Tuthill, Caroline Joyce, Juan Pablo Kaski, Fiona E. Karet Frankl, Lou A. Metherell, Ada E. D. Teo, Mark Gurnell, Laila Parvanta, William M. Drake, Eva Wozniak, David Klinzing, Jyn Ling Kuan, Zenia Tiang, Celso E. Gomez Sanchez, Per Hellman, Roger S. Y. Foo, Charles A. Mein, Veronica A. Kinsler, Peyman Bjorklund, Helen L. Storr, Maria-Christina Zennaro, Morris J. Brown
Summary: The study identified gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. These mutations were often found in patients during puberty, pregnancy, or menopause, with elevated LHCGR expression. While most aldosterone-producing adenomas have gain-of-function somatic mutations, the presence of these mutations in aldosterone-producing cell clusters of normal adrenal glands indicates a necessity for codriver mutations in APAs.
Article
Peripheral Vascular Disease
Kuan-Ming Chen, Yu-Ling Chang, Tung-Hsin Wu, Bo-Ching Lee, Po-Ting Chen, Kao-Lang Liu, Jia-Sheng Hong, Chin-Chen Chang, Vin-Cent Wu, Yen-Hung Lin
Summary: This study found that patients with APA harboring KCNJ5 mutations had a significantly lower prevalence of MetS and smaller distribution in waist circumference, SAT, and VAT. Logistic regression analysis showed that VAT area correlated significantly with KCNJ5 mutations among the APAs. After 1-year postadrenalectomy, only participants with KCNJ5 mutations had significant increases in triglycerides, cholesterol, SAT, and VAT.
JOURNAL OF HYPERTENSION
(2021)
Article
Peripheral Vascular Disease
Vin-Cent Wu, Kang-Yung Peng, Yu-Ping Kuo, Hsuan Liu, Bertrand Chin-Ming Tan, Yen-Hung Lin, Tai-Shuan Lai, Yung-Ming Chen, Jeff S. Chueh
Summary: In patients with unilateral primary aldosteronism, the coexistence of aldosterone-producing micronodules/nodules may have a negative impact on clinical success, as these patients are more likely to have persistent hypertension post-adrenalectomy. This may be explained by the attenuated HTR2B-mediated PLC/IP3/Ca2(+) pathway in Group A adenomas, as revealed by pathway enrichment analysis based on RNA-seq data.
Article
Multidisciplinary Sciences
Ravi Kumar Dutta, Malin Larsson, Thomas Arnesen, Anette Heie, Martin Walz, Piero Alesina, Oliver Gimm, Peter Soderkvist
Summary: This study identified a susceptibility locus on chromosome Xq13.3 associated with APAs using a GWAS approach. Direct genotyping of a sentinel SNP in a replication cohort showed strong significance, and sequencing of an adjacent gene revealed a rare variant. Investigation of expression quantitative trait loci provided insights into the genetic basis and potential novel mechanistic explanations for the association of the SNPs with APAs.
SCIENTIFIC REPORTS
(2021)
Review
Peripheral Vascular Disease
Fabrizio Buffolo, Silvia Monticone, Giovanni Camussi, Elena Aikawa
Summary: Extracellular vesicles (EVs) are membrane-bound structures released by cells that play a pathological role in vascular damage. They facilitate cell-to-cell communication by transferring nucleic acids, protein cargos, and metabolites. EVs promote endothelial dysfunction, vascular inflammation, and contribute to plaque formation and vascular calcification.
Review
Endocrinology & Metabolism
Tracy Ann Williams, Martin Reincke
Summary: Primary aldosteronism can be sporadic or familial, with treatment approach depending on unilateral or bilateral forms; however, disease pathology is not accurately reflected by this classification. Surgical removal of the overactive adrenal in unilateral PA achieves highly successful outcomes, with almost all patients biochemically cured of their aldosteronism.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Geriatrics & Gerontology
Dhara Patel, Tae Jin Lee, Sandeep Kumar, Sagar Vyavahare, Alison Worth, William D. Hill, Mark Hamrick, Carlos M. Isales, Rahul S. Shinde, Sadanand Fulzele
Summary: Understanding the pathophysiology of age-related diseases is crucial as the elderly population grows. Metabolic changes play an important role in age-related degeneration, affecting musculoskeletal health. Gender-specific differences in metabolic signaling pathways may contribute to the manifestation of musculoskeletal diseases in males and females.
Article
Plant Sciences
Sara Vitalini, Stefania Garzoli, Francesca Sisto, Raffaele Pezzani, Maria Pia Argentieri, Alessio Scarafoni, Salvatore Ciappellano, Maira Zorzan, Jessica Capraro, Daniela Collazuol, Marcello Iriti
Summary: This study confirms the beneficial effects of Achillea erba-rotta subsp. moschata on the gastrointestinal system and provides scientific evidence for its traditional use. The extract and essential oil from Achillea erba-rotta subsp. moschata showed antimicrobial activity against Helicobacter pylori and exerted cytotoxic effects on certain cell lines. Additionally, the extracts exhibited anti-inflammatory potential.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Transplantation
Jacopo Burrello, Silvia Monticone, Alessio Burrello, Sara Bolis, Carlotta Pia Cristalli, Giorgia Comai, Valeria Corradetti, Cristina Grange, Giuseppe Orlando, Massimiliano Bonafe, Gaetano La Manna, Lucio Barile, Benedetta Bussolati
Summary: This study explored the use of extracellular vesicle (EV) surface antigens as potential predictors of kidney transplant outcome. It found that endothelial cells and platelet markers in serum EVs were higher in patients with persistent kidney dysfunction, while mesenchymal progenitor cell markers in urine EVs increased in patients with renal recovery. These markers correlated with kidney function indicators and were able to predict patient outcomes.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
Yun Su, Xing Chen, Hongyan Zhou, Sean Shaw, Jie Chen, Carlos M. Isales, Jing Zhao, Xingming Shi
Summary: Glucocorticoids are potent drugs with anti-inflammatory and immunosuppressive effects, but their clinical use is limited due to severe side effects. The molecular mechanisms underlying glucocorticoid-induced bone loss are unclear. In this study, RNA sequencing analysis identified Xist as a glucocorticoid-regulated gene involved in glucocorticoid-induced osteoporosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Alexis M. Stranahan, De-Huang Guo, Masaki Yamamoto, Caterina M. Hernandez, Hesam Khodadadi, Babak Baban, Wenbo Zhi, Yun Lei, Xinyun Lu, Kehong Ding, Carlos M. Isales
Summary: Preferential energy storage in subcutaneous adipose tissue (SAT) provides protection against obesity-induced pathophysiology in females. Differences in adipose tissue distribution before obesity onset determine susceptibility to inflammation in males and females, independent of sex hormones.
Article
Peripheral Vascular Disease
Siyuan Gong, Martina Tetti, Elisabeth Kemter, Mirko Peitzsch, Paolo Mulatero, Martin Bidlingmaier, Graeme Eisenhofer, Eckhard Wolf, Martin Reincke, Tracy Ann Williams
Summary: TSPAN12 is a protein that is associated with the renin-angiotensin system and plays a negative regulatory role in the overproduction of aldosterone in primary aldosteronism.
Review
Endocrinology & Metabolism
Elisa Sconfienza, Martina Tetti, Vittorio Forestiero, Franco Veglio, Paolo Mulatero, Silvia Monticone
Summary: This study investigated the prevalence of autonomous/possible autonomous cortisol secretion (ACS), primary aldosteronism (PA), pheochromocytoma (PHEO), and Cushing syndrome (CS) in patients with adrenal incidentaloma (AI). The overall prevalence of functioning AIs was 27.5%, with ACS/possible ACS being the most frequent hormonal alteration (prevalence of 11.7%) and PA occurring in 4.4% of the patients. Asian patients had a higher prevalence of PA, while ACS/possible ACS had a lower prevalence in Asian countries. The prevalence of ACS/possible ACS was influenced by the proportion of female patients, while the prevalence of PA was positively associated with hypertension and the publication year. The prevalence of PHEO and CS were 3.8% and 3.1% respectively. Rating: 9/10.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Editorial Material
Biochemistry & Molecular Biology
Tracy Ann Williams, Martin Reincke
Summary: A clinical trial demonstrates the possibility of using noninvasive imaging to diagnose a surgically treatable subtype of primary aldosteronism, which is a common and often inadequately addressed form of hypertension.
Review
Cell Biology
Javad Sharifi-Rad, Veronique Seidel, Michalak Izabela, Margalida Monserrat-Mequida, Antoni Sureda, Valeska Ormazabal, Felipe A. Zuniga, Shivaprasad Shetty Mangalpady, Raffaele Pezzani, Alibek Ydyrys, Gulmira Tussupbekova, Miquel Martorell, Daniela Calina, William C. Cho
Summary: Cancer is a leading cause of death worldwide, and its development is linked to oxidative stress. The transcription factor Nrf2 plays a vital role in protecting cells against oxidative stress in cancer growth, progression, and therapy resistance. Therefore, innovative inhibitors targeting Nrf2 are being investigated. This comprehensive review explores the potential of phenolic compounds, found in traditional plant-based remedies, as effective anticancer agents by inhibiting Nrf2. The clinical applications of naturally-occurring bioactive compounds as Nrf2 inhibitors, specifically polyphenols, are also discussed.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biology
P. Robinson Muller, Tae Jin Lee, Wenbo Zhi, Sandeep Kumar, Sagar Vyavahare, Ashok Sharma, Vikas Kumar, Carlos M. Isales, Monte Hunter, Sadanand Fulzele
Summary: Osteoarthritis is a common degenerative joint disease that primarily affects females. Research has shown that the protein composition of synovial fluid in female osteoarthritis patients differs, which may provide insights into gender-specific pathophysiology.
Article
Genetics & Heredity
Juilee Rege, Sascha Bandulik, Kazutaka Nanba, Carla Kosmann, Amy R. Blinder, Allein Plain, Pankaj Vats, Chandan Kumar-Sinha, Antonio M. Lerario, Tobias Else, Yuto Yamazaki, Fumitoshi Satoh, Hironobu Sasano, Thomas J. Giordano, Tracy Ann Williams, Martin Reincke, Adina F. Turcu, Aaron M. Udager, Richard Warth, William E. Rainey
Summary: This study identified mutations in the SLC30A1 gene associated with PA. The mutations are located near the zinc-binding site in the coding region of SLC30A1 and may cause abnormal ion transport. PA cases with SLC30A1 mutations showed male dominance and increased levels of aldosterone and 18-oxocortisol.
Article
Endocrinology & Metabolism
Laura Carbone, Petra Buzkova, Howard A. Fink, John A. Robbins, Joshua Barzilay, Rachel E. Elam, Carlos Isales
Summary: Amino acids are important for skeletal health, and the relationship between tryptophan and its metabolites with hip fractures and mortality has been examined. Higher serum levels of tryptophan were associated with lower risk of hip fractures, but no significant associations were found with mortality or frailty status. Further randomized clinical trials are needed to investigate the potential benefits of increased tryptophan intake for osteoporosis.
Meeting Abstract
Neurosciences
Christian Adolf, Harald Murck, Anna-Lina Sarkis, Tracy Ann Williams, Martin Reincke, Heike Kuenzel
BIOLOGICAL PSYCHIATRY
(2022)