Related Experiment Video
Updated: Apr 3, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations
Ada E D Teo1, Sumedha Garg, Lalarukh Haris Shaikh
1From the Clinical Pharmacology Unit, Centre for Clinical Investigation, Addenbrooke's Hospital, University of Cambridge (A.E.D.T., S.G., L.H.S., J.Z., E.A.B.A., M.J.B.), Department of Medical Genetics, Division of Renal Medicine, University of Cambridge (F.E.K.F.), University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science, Addenbrooke's Hospital (M.G.), Department of Pathology, Addenbrooke's Hospital (L.H., A.M.), and MRC Laboratory of Molecular Biology (M.B.) - all in Cambridge, United Kingdom; and the Department of Medicine, National University of Malaysia Medical Centre, Kuala Lumpur (E.A.B.A.).
Abstract:
Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).
Insights
New subtypes of aldosterone-producing adenomas linked to CTNNB1 mutations were identified. These adenomas in women with hyperaldosteronism express high levels of gonadal receptors, impacting cell differentiation.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism.
- Somatic mutations are increasingly recognized as drivers of APA heterogeneity.
- Understanding these mutations is crucial for diagnosing and treating hyperaldosteronism.
Observation:
- Three women with hyperaldosteronism, presenting during pregnancy or post-menopause, were studied.
- Their APAs exhibited activating mutations in CTNNB1, which encodes beta-catenin.
- These tumors showed significantly elevated expression of LHCGR and GNRHR, encoding gonadal receptors.
Findings:
- Activating CTNNB1 mutations in APAs stimulate the Wnt signaling pathway.
- This Wnt activation promotes the de-differentiation of adrenocortical cells.
- The de-differentiation appears to revert cells towards a common adrenal-gonadal precursor phenotype.
Implications:
- Identifies novel APA subtypes associated with specific mutations and clinical contexts.
- Suggests a link between Wnt pathway activation, gonadal receptor expression, and APA development.
- Provides new insights into the pathogenesis of hyperaldosteronism and potential therapeutic targets.
Related Concept Videos
01:27Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:33Hormonal Regulation
01:17Antihypertensive Drugs: Action of β1 Blockers
01:31Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase