Dataset Information

Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism.

ABSTRACT:

Background

Normal-appearing adrenal glands on cross-sectional imaging may still be the source of aldosterone production in primary aldosteronism (PA).

Methods

We evaluated the prevalence of aldosterone production among morphologically normal-appearing adrenal glands and the impact of this phenomenon on interpretations of localization studies and treatment decisions. We performed a retrospective cohort study of PA patients with at least 1 normal adrenal gland and reanalyzed contemporary studies to assess interpretations of imaging and adrenal venous sampling (AVS) at the individual patient and adrenal levels.

Results

Among 243 patients, 43 (18%) had bilateral normal-appearing adrenals and 200 (82%) had a unilateral normal-appearing adrenal, for a total of 286 normal-appearing adrenal glands. 38% of these normal-appearing adrenal glands were a source of aldosteronism on AVS, resulting in discordance between imaging and AVS findings in 31% of patients. Most patients with lateralizing PA underwent curative unilateral treatment (80%); however, curative treatment was pursued in 92% of patients who had concordant imaging-AVS results but in only 38% who had discordant results (P < 0.05). In young patients, imaging-AVS discordance was detected in 32% of those under 45 years and 21% of those under 35 years. Among 20 contemporary studies (including 4,904 patients and 6,934 normal-appearing adrenal glands), up to 64% of normal-appearing adrenals were a source of aldosteronism resulting in 31% of patients having discordant results.

Conclusions

Morphologically normal-appearing adrenal glands are commonly the source of aldosterone production in PA, even among young patients. The lack of awareness of this issue may result in inappropriate treatment recommendations.

SUBMITTER: Parksook WW

PROVIDER: S-EPMC9890245 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism.

Parksook Wasita W WW Yozamp Nicholas N Hundemer Gregory L GL Moussa Marwan M Underhill Jonathan J Fudim Tali T Sacks Barry B Vaidya Anand A

American journal of hypertension 20220601 6

<h4>Background</h4>Normal-appearing adrenal glands on cross-sectional imaging may still be the source of aldosterone production in primary aldosteronism (PA).<h4>Methods</h4>We evaluated the prevalence of aldosterone production among morphologically normal-appearing adrenal glands and the impact of this phenomenon on interpretations of localization studies and treatment decisions. We performed a retrospective cohort study of PA patients with at least 1 normal adrenal gland and reanalyzed contemp ...[more]

PMID: 34883509

Similar Datasets

Project description:Primary aldosteronism (PA) is the most common endocrine hypertension comprising 10% of hypertensive patients. A recent series of transcriptome analyses using DNA microarray has shown that neumerous genes are differentially expressed between aldosterone-producing adenoma (APA) and its adjacent adrenal gland (AAG) tissue from the same patient. However, the molecular mechanism(s) of pathogenesis of APA has not yet been fully clarified. Although growing body of evidence has shown that epigenetic abnormalities including DNA methylation play a key role in tumorigenesis, there are few studies with regard to DNA methylation in APA. In the present study, to elucidate the pathogenic relationship between gene expression and DNA methylation in PA, we conducted an integrated analysis of transcriptome and methylome data for paired APA-AAG samples from the same patient. Adrenal specimens were obtained from 7 Japanese patients with APA, who underwent adrenalectomy at Tokyo Medical and Dental University. RNA and DNA samples were extracted from those 7 paired APA and AAG tissues. Gene expression and genome-wide DNA methylation profiles were obtained using SurePrint G3 Human GE 8x60K Microarray (Agilent) and Infinium HumanMethylation450 Beadchip (Illumina), respectively. Transcriptome anlaysis identified 244 significantly (2 fold<) upregulated genes in APA compared to AAG. The upregulated genes include the previously studied genes such as PCP4, ALDH1A2, and CYP11B2, and other genes that have not been previously studied, such as HOXA9, HOXA11, and HOXB9. Gene ontology (GO) analysis for these upregulated genes identified the calcium signaling pathway to be most significantly enriched with the upregulated genes (8 genes). Methylome analysis revealed that APA was globally hypomethylated compared to AAG regardless of gene feature groups, namely, TSS1500, TSS200, 5’UTR, 1stExon, gene body, and 3’UTR. GO analysis for the genes showing hypomethylation at TSS1500/TSS200 regions in APA identified the term “cytokine-cytokine receptor interaction” to be most significantly enriched with hypomethylated genes (37 genes). Integrated analysis of gene expression and genome-wide DNA methylation profiles identified 18 genes that are upregulated and whose TSS1500/TSS200 regions are hypomethylated in APA compared to AAG. These genes include CYP11B2 and MC2R (ACTH receptor). In conclusion, this is the first genome-wide study for PA that integrated transcriptome and methylome data. Global DNA hypomethylation in APA and concordant transcriptional up-regulation of some key genes, such as CYP11B2 and MC2R, may play crucial roles in the pathophysiological significance in PA.

Dataset Information

Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism.

Background

Methods

Results

Conclusions

Publications

Morphologically Normal-Appearing Adrenal Glands as a Prevalent Source of Aldosterone Production in Primary Aldosteronism.

Similar Datasets

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