Pseudohypoadrenalism, a Subclinical Cortisol Metabolism Disorder in Hyperuricemia

Authors

• Ruixia Bao
• Beibei Chen
• Jujie Pan
• Alexander Wang
• Haiyang Yu
• Qian Chen
• Yi Zhang
• Tao Wang

Language

English

Publication Date

1-1-2023

Journal

Frontiers in Endocrinology

DOI

10.3389/fendo.2023.1279205

PMID

38034015

PMCID

PMC10687422

PubMedCentral® Posted Date

11-16-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Hyperuricemia is a known risk factor of lipid metabolism disorder. However, the mechanisms have not been fully understood.

Methods: The serum samples from hyperuricemia subjects were used to analyze the correlation between serum uric acid and clinical characteristics. Hyperuricemia mice induced by potassium oxonate (PO) and adenine were used to explore glucocorticoid metabolism.

Results: In hyperuricemia patients, the levels of serum uric acid were positively correlated with the levels of γ-glutamyltransferase, associated with a cortisol metabolism disorder. In hyperuricemia state, the adrenal glands failed to respond to adrenocorticotropic hormone properly, leading to low cortisol, but not corticosterone production, and decreased mRNA levels of aldosterone synthase, 11β-hydroxylase, and 3β-hydroxysteroid dehydrogenase 1, three key enzymes for cortisol synthesis. The expression of both hepatic 5α-reductase and renal 11β-hydroxysteroid dehydrogenase 2 was significantly reduced, which led to low cortisol clearance. We denominated this cortisol metabolism disorder in hyperuricemia as pseudohypoadrenalism (PHAL).

Conclusion: PHAL increased exposure to the bioavailable cortisol in the liver, leading to local amplification of the biological action of corticosteroids. Unregulated biosynthesis pathway of bile acid expanded bile acid pool, and further aggravated cholestatic liver injury.

Keywords

Humans, Animals, Mice, Hydrocortisone, Uric Acid, Hyperuricemia, 11-beta-Hydroxysteroid Dehydrogenases, Metabolic Diseases, Bile Acids and Salts

Published Open-Access

yes

Recommended Citation

Bao, Ruixia; Chen, Beibei; Pan, Jujie; et al., "Pseudohypoadrenalism, a Subclinical Cortisol Metabolism Disorder in Hyperuricemia" (2023). Faculty, Staff and Student Publications. 6742.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6742