ArticleThe Journal of clinical endocrinology and metabolism2020
Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- [Nature medicine · 2023Trial
- Aldosterone-Producing Lesions HarboringHypertension (Dallas, Tex. : 1979) · 2026Article
- Targeting Plasma Membrane CaCancers · 2026Review
- Prediction Model and Score for Subtyping Primary Aldosteronism: Development and Multi-Cohort Validation.JACC. Asia · 2026Article
- Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025Article
- Unilateral Primary Aldosteronism: Long-Term Disease Recurrence After Adrenalectomy.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Shifting paradigms in primary aldosteronism: reconsideration of screening strategy via integrating pathophysiological insights.Frontiers in endocrinology · 2024Review
- Germline de novo variant F747S extends the phenotypic spectrum of CACNA1D Ca2+ channelopathies.Human molecular genetics · 2023Article
- In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride Cotransporter.Kidney360 · 2022Article
- Intrinsic Adrenal TWIK-Related Acid-Sensitive TASK Channel Dysfunction Produces Spontaneous Calcium Oscillations Sufficient to Drive AngII (Angiotensin II)-Unresponsive Hyperaldosteronism.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Histopathology and Genetic Causes of Primary Aldosteronism in Young Adults.The Journal of clinical endocrinology and metabolism · 2022Article
- Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation.Frontiers in endocrinology · 2022Review
- Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome.Frontiers in endocrinology · 2022Review
- GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas.European journal of endocrinology · 2021Review
- Intraindividual Variability of Aldosterone Concentrations in Primary Aldosteronism: Implications for Case Detection.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Variability of Aldosterone Measurements During Adrenal Venous Sampling for Primary Aldosteronism.American journal of hypertension · 2021Article
- Approaches to Gene Mutation Analysis Using Formalin-Fixed Paraffin-Embedded Adrenal Tumor Tissue From Patients With Primary Aldosteronism.Frontiers in endocrinology · 2021Review
- Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs.The Journal of clinical endocrinology and metabolism · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
CONTEXT AND
objectivePosture-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.
methodsPlasma 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.
resultsPatients 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 [20.0%], and ATP2B3 = 2 [5.0%]), including 5 previously unreported mutations (3 in CACNA1D and 2 in ATP1A1). Notably, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 56.5% (13/23) of posture-unresponsive APAs harbored KCNJ5 mutations.
conclusionsThe elevated production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol, which acts as the substrate for CYP11B2-generated hybrid steroids.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.