Ambulatory microdialysis sampling revealed pulsatile nocturnal hypersecretion of aldosterone and hybrid steroids with preserved daily rhythm in primary aldosteronism, confirming that 'a key pathophysiological feature of primary aldosteronism is disruption of corticosteroid rhythms rather than persistent elevation of hormones.'
Key Findings
Results
Primary aldosteronism is characterized by pulsatile nocturnal hypersecretion of aldosterone rather than persistent elevation throughout the day.
Continuous 24-hour ambulatory microdialysis sampling was used to monitor tissue corticosteroid dynamics in a cohort of 60 patients.
Nocturnal hypersecretion was pulsatile in nature, occurring predominantly during sleep.
Despite nocturnal hypersecretion, a preserved daily rhythm of aldosterone was observed.
The finding confirms that 'a key pathophysiological feature of primary aldosteronism is disruption of corticosteroid rhythms rather than persistent elevation of hormones.'
Results
Nocturnal hypersecretion of the hybrid steroids 18-hydroxycortisol and 18-oxocortisol was also found in primary aldosteronism.
Both 18-hydroxycortisol and 18-oxocortisol showed pulsatile nocturnal hypersecretion alongside aldosterone.
These hybrid steroids were monitored continuously over 24 hours using ambulatory microdialysis.
The dysregulation of these hybrid steroids, like aldosterone, was most prominent during sleep.
Results
Corticosteroid rhythm dysregulation was most prominent in patients with unilateral primary aldosteronism.
Unilateral disease showed the most pronounced nocturnal pulsatile hypersecretion compared to other disease subtypes.
Normalization of corticosteroid rhythms occurred after adrenalectomy in patients with unilateral disease.
This normalization post-adrenalectomy supports the causal role of unilateral adrenal overproduction in the observed rhythm disruption.
Results
Ambulatory microdialysis provides substantially more diagnostic information than current single-time point hormone measurements.
The technique allows continuous monitoring of tissue corticosteroid dynamics over 24 hours.
Current diagnostic pathways rely on single-time point hormone measurements and do not capture alterations in the dynamics of aldosterone secretion.
The study was described as a 'proof-of-concept' demonstrating that 'ambulatory dynamic hormone profiling is a viable technique.'
The authors note this approach offers 'the opportunity to investigate more subtle dynamic phenotypes and potentially earlier detection of disease.'
Background
Primary aldosteronism affects 5 to 20% of the hypertensive population and is frequently missed by current diagnostic approaches.
The prevalence is estimated at 5 to 20% of the hypertensive population.
Primary aldosteronism is associated with increased cardiovascular and metabolic risk compared with primary hypertension.
Alterations in the dynamics of aldosterone secretion 'are not well captured by current diagnostic pathways, and the disease is often missed.'
What This Means
This research suggests that primary aldosteronism — a hormonal condition caused by the adrenal glands overproducing aldosterone, affecting up to 1 in 5 people with high blood pressure — causes its hormonal disruption primarily at night during sleep, rather than continuously throughout the day. Using a wearable device that samples fluid from beneath the skin every few minutes over a full 24-hour period, researchers tracked aldosterone and related hormone levels in 60 patients. They found that these hormones surged in unpredictable bursts specifically during nighttime hours, while daytime rhythms appeared relatively preserved. This finding challenges the assumption that the disease simply causes persistently high hormone levels at all times.
The study also found that patients with disease in only one adrenal gland showed the most dramatic nighttime hormone surges, and that these surges returned to normal after surgical removal of the affected gland. This supports the idea that the abnormal gland is responsible for the disrupted nighttime hormone secretion. The researchers used a wearable microdialysis device — a thin tube placed just under the skin — to collect these continuous hormone measurements, an approach not typically used in clinical practice.
This research suggests that standard diagnostic tests, which measure hormone levels at a single point in time, may miss key features of primary aldosteronism because the worst abnormalities happen at night when patients are asleep and not being tested. Continuous monitoring could potentially detect the disease earlier or more reliably, and might help explain why primary aldosteronism carries higher risks for heart disease and metabolic problems than regular high blood pressure, possibly because of the disrupted nighttime hormone patterns.
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Grytaas M, Upton T, Marinelli I, Methlie P, Øksnes M, Vassiliadi D, et al.. (2026). Tissue corticosteroid rhythms are dysregulated predominantly during sleep in primary aldosteronism.. Science translational medicine. https://doi.org/10.1126/scitranslmed.aeb7517