Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs.

The Journal of Clinical Endocrinology and Metabolism
Zeng GuoMichael Stowasser

Abstract

Posture-responsive and posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these 2 types of APA. Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by liquid chromatography-tandem mass spectrometry. Immunohistochemistry for CYP11B2 (aldosterone synthase) and CYP17A1 (17α-hydroxylase) and deoxyribonucleic acid sequencing (Sanger and next-generation sequencing) were performed on APA tissue collected from 23 posture-unresponsive and 17 posture-responsive APA patients. Patients with posture-unresponsive APA displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, larger (P < 0.01) zona fasciculata (ZF)-like tumors with higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2) than patients with posture-responsive APA (most of which were not ZF-like). Of 40 studied APAs, 37 (92.5%) were found to harbor aldosterone-driving somatic mutations (KCNJ5 = 14 [35.0%], CACNA1D = 13 [32.5%], ATP1A1 = 8...Continue Reading

References

Jul 1, 1976·The Journal of Clinical Endocrinology and Metabolism·M SchambelanE G Biglieri
Jul 1, 1992·The Journal of Clinical Endocrinology and Metabolism·K NomuraH Demura
Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T KawamotoH Imura
Sep 1, 1991·American Journal of Hypertension·R G FontesI Irony
Jul 1, 1990·Biological Psychiatry·K R KrishnanB J Carroll
Jul 1, 1990·American Journal of Hypertension·I IronyC H Shackleton
Mar 1, 1987·Clinical and Experimental Pharmacology & Physiology·R D GordonS A Klemm
Nov 1, 1973·The Journal of Clinical Endocrinology and Metabolism·A GangulyA J Dowdy
Feb 1, 1973·The Journal of Clinical Endocrinology and Metabolism·A GangulyG A Melada
Mar 1, 1967·The Journal of Clinical Investigation·E L CohenD R Rovner
Nov 1, 1984·The Journal of Clinical Endocrinology and Metabolism·C E Gomez-SanchezM H Weinberger
Apr 1, 1994·Clinical and Experimental Pharmacology & Physiology·M StowasserR D Gordon
May 1, 1993·Clinical and Experimental Pharmacology & Physiology·T J TunnyR D Gordon
Jun 1, 1995·Clinical and Experimental Pharmacology & Physiology·M StowasserR D Gordon
Jun 1, 1996·Clinical and Experimental Pharmacology & Physiology·M StowasserR D Gordon
Nov 1, 1996·Endocrine Research·L BreaultN Gallo-Payet
Feb 1, 1997·Biological Psychiatry·A Gudmundsson, M Carnes
Oct 12, 2001·The Journal of Steroid Biochemistry and Molecular Biology·M Stowasser, R D Gordon
Aug 14, 2003·The Journal of Clinical Endocrinology and Metabolism·E A EspinerP J Hunt
Mar 6, 2004·The Journal of Clinical Endocrinology and Metabolism·Paolo MulateroWilliam F Young
May 12, 2004·Molecular and Cellular Endocrinology·Michael Stowasser, Richard D Gordon
Dec 13, 2006·Journal of the American College of Cardiology·Gian Paolo RossiUNKNOWN PAPY Study Investigators
May 12, 2007·Clinical Endocrinology·William F Young
May 29, 2008·The Journal of Clinical Endocrinology and Metabolism·David S GellerRichard P Lifton
Aug 8, 2008·The Journal of Clinical Endocrinology and Metabolism·Paolo Mulatero
Mar 5, 2010·The Journal of Clinical Endocrinology and Metabolism·Koshiro NishimotoKuniaki Mukai
Dec 3, 2011·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·A Hannemann, H Wallaschofski
Jan 26, 2012·Hypertension·Sheerazed BoulkrounMaria-Christina Zennaro
Feb 22, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Michael Stowasser
Aug 6, 2013·Nature Genetics·Elena A B AzizanMorris J Brown
May 20, 2014·Molecular and Cellular Endocrinology·Yasuhiro NakamuraHironobu Sasano
May 29, 2014·Hypertension·Fabio Luiz Fernandes-RosaMaria-Christina Zennaro

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Citations

Aug 28, 2020·The Journal of Clinical Endocrinology and Metabolism·Kazutaka NanbaHironobu Sasano
Nov 13, 2020·American Journal of Hypertension·Nicholas YozampAnand Vaidya

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