title: Expression of aldosterone synthase and adrenocorticotropic hormone receptor             in adrenal incidentalomas from normotensive and hypertensive patients: Distinguishing             subclinical or atypical primary aldosteronism from adrenal incidentaloma.
abstract: The present study aimed to investigate the expression of aldosterone synthase (CYP11B2), adrenocorticotropic hormone receptor (ACTH-R) and their regulating transcription factors in adrenal incidentalomas (AIs) from normotensive and hypertensive patients to distinguish subclinical or atypical primary aldosteronism (PA) from AIs. Total RNA was extracted from 8 normal adrenal cortices (NAs), 46 AIs, 15 aldosterone-producing adenomas (APAs) and 6 idiopathic hyperaldosteronisms (IHAs). Real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry were performed to determine the mRNA and protein expression of CYP11B2, ACTH-R, steroidogenic factor-1 (SF1) and dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene-1 (DAX-1) in the different tissues. The AI hypertensive subgroup displayed increased plasma aldosterone concentration (PAC) and PAC/PRA ratio (ARR) and decreased plasma renin activity (PRA) compared to the normotensive group. CYP11B2, ACTH-R and SF1 mRNAs were signiﬁcantly higher in the APA group compared to the other groups, and gradually increased in AI hypertensive samples. DAX-1 mRNA was expressed faintly in PA compared with NA. In normotensive-AI samples, DAX-1 mRNA was higher compared to PA and AI hypertensive samples. Significant differences in gene expression levels in AIs were observed between probable and improbable PA patients. Immunohistochemical results were consistent with those of real-time PCR. Plasma aldosterone levels were positively correlated with CYP11B2, ACTH-R and SF1 mRNA and inversely correlated with DAX-1 mRNA. In conclusion, a significant number of hypertensive-AI patients may have subclinical forms of PA. CYP11B2, ACTH-R and their regulating transcription factors may be noteworthy in distinguishing subclinical PA from AIs.
authors.affiliation: Department of Endocrinology, The Affiliated Hospital of the Medical                     College of Qingdao University, Shandong, Qingdao 266100, P.R. China.
authors.forename: C X
authors.initials: CX
authors.lastname: Cao
authors.forename: X C
authors.initials: XC
authors.lastname: Yang
authors.forename: Y X
authors.initials: YX
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Zhuang
authors.forename: K P
authors.initials: KP
authors.lastname: Wang
authors.forename: L J
authors.initials: LJ
authors.lastname: Sun
authors.forename: X S
authors.initials: XS
authors.lastname: Wang
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D000450:Aldosterone / Q000097:blood; D058070:Asymptomatic Diseases; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D006973:Hypertension / Q000097:blood / Q000201:enzymology*; D033162:Incidental Findings; D008297:Male; D008875:Middle Aged; D000072260:RNA Splicing Factors; D018043:Receptors, Corticotropin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D000072260:RNA Splicing Factors; D018043:Receptors, Corticotropin; C107467:SF1 protein, human; D014157:Transcription Factors; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2