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High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.

ABSTRACT: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS), which has been associated with ectopic G-protein coupled receptors (GPCRs) in the adrenal cortex. We recently studied a 51-year-old male with PBMAH who presented with severe CS and hyperestronemia, manifesting clinically with a Cushingoid appearance, gynecomastia, and telangiectasias. Analysis of adrenal tissues following bilateral adrenalectomy showed high expression of P450 aromatase (CYP19A1). The patient carried a germline non-sense pathogenic variant in ARMC5 (p.R173*), with two independent somatic pathogenic variants identified in the right (p.S571*) and left (p.Q235*) adrenal tissues, respectively. The expression of ARMC5 was drastically decreased in the hyperplastic regions when compared to either the adjacent non-hyperplastic regions and samples from PBMAH without pathogenic variants in ARMC5. We found expression of CYP19A1 in other cases of PBMAH, although there were no differences in aromatase expression between ARMC5-mutant and ARMC5-non-mutant cases. We conclude that in select cases, PBMAH can be associated with aromatase expression resulting in elevated estrogens, irrespective of sex. Additionally, CYP19A1 expression does not appear to depend on the ARMC5 variant status.

SUBMITTER: Berthon A

PROVIDER: S-EPMC6615475 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.

Berthon Annabel A Hannah-Shmouni Fady F Maria Andrea Gutierrez AG Faucz Fabio R FR Stratakis Constantine A CA

The Journal of steroid biochemistry and molecular biology 20190420

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing syndrome (CS), which has been associated with ectopic G-protein coupled receptors (GPCRs) in the adrenal cortex. We recently studied a 51-year-old male with PBMAH who presented with severe CS and hyperestronemia, manifesting clinically with a Cushingoid appearance, gynecomastia, and telangiectasias. Analysis of adrenal tissues following bilateral adrenalectomy showed high expression of P ...[more]

PMID: 31014964

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Project description:ContextRadiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated.ObjectiveWe hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed.DesignA retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019.SettingTertiary care clinical research center.PatientsPatients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics.InterventionClinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota).Main outcome and measures17-hydroxycorticosteroids (17-OHS), ARMC5 genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume.ResultsA cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76, P = 0.028), urinary free cortisol (R = 0.70, P = 0.035), and 17-OHS (R = 0.87, P = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in ARMC5 (R = 0.72, P = 0.018; R = 0.65, P = 0.042; and R = 0.73, P = 0.016, respectively).ConclusionsVolumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.

Dataset Information

High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.

Publications

High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.

Similar Datasets

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