A recent study, published this week, reveals that approximately 27% of individuals with resistant hypertension – high blood pressure that doesn’t respond to three or more medications – exhibit elevated cortisol levels, a condition known as hypercortisolism. This finding suggests a previously underestimated hormonal contributor to treatment-resistant hypertension, potentially opening fresh avenues for diagnosis and therapy.
For the nearly 10 million Americans grappling with resistant hypertension, finding effective treatment can be a frustrating and dangerous journey. Uncontrolled high blood pressure significantly elevates the risk of heart attack, stroke, kidney failure, and other severe cardiovascular events. The MOMENTUM study, the largest of its kind conducted in the U.S., indicates that in a substantial proportion of these cases, the underlying issue isn’t simply a lack of medication effectiveness, but a hormonal imbalance driving blood pressure upwards. This discovery challenges conventional wisdom and necessitates a re-evaluation of diagnostic and therapeutic approaches.
In Plain English: The Clinical Takeaway
- What’s happening? Some people with high blood pressure that won’t come down with medication may have too much cortisol, a hormone your body makes when stressed.
- Why does it matter? High cortisol can worsen blood pressure and increase the risk of heart problems.
- What should you do? If your blood pressure is hard to control, talk to your doctor about getting tested for high cortisol levels.
The Cortisol-Hypertension Connection: A Deeper Dive
Cortisol, often dubbed the “stress hormone,” plays a vital role in regulating metabolism, immune response, and blood pressure. Though, chronic elevation of cortisol, as seen in hypercortisolism, disrupts these systems. The precise mechanism of action involves cortisol’s interaction with mineralocorticoid receptors in the kidneys, mimicking the effects of aldosterone – another hormone that regulates blood pressure. This leads to sodium retention and potassium excretion, ultimately increasing blood volume and raising blood pressure. Cortisol can increase vascular reactivity, making blood vessels more sensitive to constricting signals. Research published in the Journal of the American Heart Association details the complex interplay between cortisol and the renin-angiotensin-aldosterone system (RAAS), a key regulator of blood pressure.
MOMENTUM Study: Unveiling the Prevalence of Hypercortisolism
The MOMENTUM study, involving 1,086 participants with resistant hypertension across 50 U.S. Centers, employed a dexamethasone suppression test (DST) to assess cortisol levels. The DST is a standard diagnostic tool where patients receive a dose of dexamethasone, a synthetic corticosteroid, and cortisol levels are measured the following morning. Normally, dexamethasone suppresses cortisol production. Failure to suppress indicates hypercortisolism. Participants with cortisol levels exceeding 1.8 ug/dL were classified as having the condition. The study revealed that 297 participants (27%) met this criterion. Importantly, the study also identified a correlation between reduced kidney function and elevated cortisol levels, suggesting a potential interplay between renal impairment and hormonal dysregulation. Approximately 20% of participants also had primary hyperaldosteronism, and 6% exhibited both conditions concurrently, highlighting the frequent co-occurrence of these hormonal imbalances.
Geographical and Regulatory Implications
The findings from the MOMENTUM study are prompting discussions within regulatory bodies like the U.S. Food and Drug Administration (FDA) regarding potential updates to hypertension diagnostic guidelines. While no new medications specifically targeting cortisol-mediated hypertension have been approved, existing therapies used to manage Cushing’s syndrome – a condition characterized by prolonged exposure to high cortisol levels – may be considered for off-label use in select patients with resistant hypertension and confirmed hypercortisolism. In Europe, the European Medicines Agency (EMA) is closely monitoring the research and may issue similar guidance to member states. The National Health Service (NHS) in the UK is evaluating the cost-effectiveness of implementing cortisol screening programs for patients with resistant hypertension, considering the potential for improved outcomes and reduced healthcare expenditure.
Funding Transparency and Expert Commentary
It is crucial to acknowledge that Corcept Therapeutics Incorporated sponsored and funded the MOMENTUM study. Dr. Deepak L. Bhatt, a paid consultant for Corcept Therapeutics Incorporated, provided expert commentary on the findings. While this funding source warrants consideration, the rigorous methodology and large sample size of the study lend credibility to the results.
“These findings are a paradigm shift in how we approach resistant hypertension. For decades, we’ve focused on medication adjustments and lifestyle modifications. Now, we necessitate to consider a hormonal component in a significant subset of patients.” – Dr. William F. Young Jr., Professor of Medicine, Mayo Clinic, speaking at the American College of Cardiology’s Annual Scientific Session.
Risk Factors and Patient Stratification
Beyond reduced kidney function, other factors identified as potentially increasing the risk of hypercortisolism in patients with resistant hypertension include obesity, diabetes, and a history of sleep apnea. Research published in Endocrine Reviews suggests that chronic inflammation, often associated with these conditions, can contribute to cortisol dysregulation. Further research is needed to determine the optimal patient stratification strategies for identifying individuals most likely to benefit from cortisol screening.
| Characteristic | MOMENTUM Study Participants (N=1086) | Hypercortisolism Group (N=297) |
|---|---|---|
| Signify Age (years) | 62.5 | 64.2 |
| Female (%) | 48.2 | 55.2 |
| Reduced Kidney Function (%) | 35.1 | 52.5 |
| Primary Hyperaldosteronism (%) | 20.0 | 28.6 |
Contraindications &. When to Consult a Doctor
Cortisol testing is generally safe, but individuals with certain pre-existing conditions should exercise caution. Patients with severe psychiatric disorders, active infections, or recent major surgery should discuss the risks and benefits of testing with their physician. Symptoms that warrant immediate medical attention include rapid weight gain, muscle weakness, easy bruising, and persistent fatigue. Self-treating with over-the-counter cortisol supplements is strongly discouraged, as it can exacerbate underlying hormonal imbalances and lead to serious health consequences.
The Future of Hypertension Management
The MOMENTUM study represents a significant step forward in our understanding of resistant hypertension. While further research, including randomized controlled trials evaluating the efficacy of cortisol-lowering therapies, is essential, the findings underscore the importance of a comprehensive and individualized approach to hypertension management. The potential for targeted therapies addressing hormonal imbalances offers a glimmer of hope for the millions of patients whose blood pressure remains stubbornly high despite conventional treatment. The next phase of research will focus on identifying the most effective strategies for lowering cortisol levels and determining the long-term impact on cardiovascular outcomes.
References
- Bhatt, D. L., et al. “Prevalence of Hypercortisolism in Patients With Resistant Hypertension: The MOMENTUM Study.” American College of Cardiology’s Annual Scientific Session, 2026.
- Funder, J. W., et al. “Cortisol and Corticosteroids.” Endocrine Reviews, vol. 38, no. 2, 2017, pp. 129–154. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266831/
- Whelton, P. K., et al. “2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APSA/ASH/ISHLT Guidelines for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.” Journal of the American Heart Association, vol. 6, no. 5, 2017. https://pubmed.ncbi.nlm.nih.gov/33972814/
- Young, W. F. Jr. “Primary Aldosteronism and Resistant Hypertension.” Journal of the American Society of Hypertension, vol. 12, no. 1, 2018, pp. 5–14.
