Primary Aldosteronism Diagnosis and Management

Primary aldosteronism is characterised by autonomous overproduction of aldosterone by the adrenal cortex, leading to hypertension, hypokalaemia and elevated cardiovascular risk. Early identification relies on screening with the plasma aldosterone-to-renin ratio, followed by confirmatory tests such as saline infusion or fludrocortisone suppression to verify inappropriate aldosterone secretion. Subtype distinction between unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia is critical, as it dictates management. Anatomical imaging with CT or MRI may suggest lateralised disease, but adrenal vein sampling remains the reference standard to ensure precise gland localisation. Unilateral adenomas are best treated by laparoscopic adrenalectomy, often resulting in cure or marked improvement of hypertension, whereas bilateral disease is managed medically with mineralocorticoid receptor antagonists. Recent advances in molecular genetics have uncovered somatic mutations in ion channels and signalling proteins that drive aldosterone overproduction, enhancing our understanding of pathogenesis and opening avenues for targeted therapies. Medical management now emphasises careful dose titration of receptor antagonists and potassium-sparing agents, with growing attention to comorbid metabolic derangements. Multidisciplinary care, incorporating endocrinologists, radiologists and surgeons, ensures optimal long-term outcomes and minimises cardiovascular sequelae.

Research from Nature Portfolio

Recent studies have demonstrated that non-invasive functional imaging can match the accuracy of invasive sampling. A prospective trial comparing [11C]metomidate PET-CT with adrenal vein sampling in patients with unilateral disease found that the novel scan reliably predicts biochemical and clinical cure after adrenalectomy, offering a less burdensome alternative to vein cannulation. Concurrently, genomic analyses have identified recurrent somatic mutations in the cell adhesion gene CADM1 within aldosterone-producing adenomas. Functional experiments revealed that these mutations disrupt gap junction communication in zona glomerulosa cells, upregulating aldosterone synthase and establishing a new mechanistic link between cell–cell coupling and hormone overproduction.

Primary Aldosteronism Diagnosis and Management publication trend

The graph below shows the total number of articles in primary aldosteronism diagnosis and management across all publications each year (not limited to Nature Index journals).

Technical terms

Adrenal vein sampling (AVS): Measurement of aldosterone and cortisol concentrations in blood from each adrenal vein to lateralise aldosterone secretion.

Mineralocorticoid receptor antagonist (MRA): A drug class (eg spironolactone, eplerenone) that blocks aldosterone binding, reducing sodium retention and blood pressure.

Plasma aldosterone-to-renin ratio (ARR): A screening index for primary aldosteronism reflecting excessive aldosterone relative to renin.

[11C]metomidate PET-CT (MTO): A positron emission tomography technique using a radiolabelled adrenal enzyme inhibitor to localise aldosterone-producing tissue non-invasively.

Somatic mutation: A genetic change acquired by adrenal cells that can constitutively activate aldosterone production.

References

1. Diagnosis and management of primary aldosteronism: An updated review. Annals of Medicine (2013).
2. [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nature Medicine (2023).
3. Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production. Nature Genetics (2023).
4. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. The Lancet (2015).
5. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight (2017).