Key Points:
- Endogenous hypercortisolism is a treatable secondary cause of hypertension that contributes to resistant hypertension (rHTN). However, hypercortisolism has traditionally been considered rare, and its true prevalence in patients with rHTN has been uncertain.
- MOMENTUM, the first large, prospective, US-based study of hypercortisolism prevalence in rHTN, screened 1,086 patients with resistant hypertension at 50 US sites using the 1-mg overnight dexamethasone suppression test (DST).
- Hypercortisolism was present in 27.3% of patients with rHTN. Patients with hypercortisolism had significantly worse kidney function and higher rates of CKD progression, and numerically higher rates of cardiac disorders and diabetes. Markers of primary hyperaldosteronism were also present in approximately 20% of participants, with 6% demonstrating cortisol-aldosterone co-secretion.
- These findings suggest that screening for hypercortisolism alongside hyperaldosteronism should be considered in patients with resistant hypertension, as it represents a potentially treatable contributor to poor cardiometabolic outcomes in this population.
Resistant hypertension (rHTN), defined as blood pressure remaining above goal despite use of three or more antihypertensive medication classes including a diuretic, affects approximately 13% of patients with hypertension. Secondary endocrine causes such as primary hyperaldosteronism are increasingly recognized as contributors to rHTN. Endogenous hypercortisolism, or excess cortisol production, raises blood pressure through multiple pathways including RAAS activation, mineralocorticoid receptor stimulation, impaired vasodilation, and sympathetic nervous system activation, and is associated with an increased risk of myocardial infarction, stroke, and heart failure. However, much like primary hyperaldosteronism before it, hypercortisolism has historically been considered rare in this population. Prior to MOMENTUM, no large, robust, US-based study had assessed the prevalence of hypercortisolism among patients with resistant hypertension.
On March 29th 2026, the results of “Prevalence and Clinical Impact of Hypercortisolism in Individuals with Resistant Hypertension: Primary Results from the MOMENTUM Study” were presented at the American College of Cardiology Scientific Sessions in New Orleans, LA. The purpose of this study was to determine the prevalence of hypercortisolism among patients with rHTN and to characterize its associated clinical and laboratory features.
MOMENTUM was a prospective observational study conducted at 50 sites across the United States, funded by Corcept Therapeutics [NCT06829537]. Adults aged 18–80 years with rHTN based on 2017 AHA criteria – defined as systolic blood pressure (SBP) ≥130 mmHg despite use of ≥3 antihypertensive medication classes including a diuretic at maximally tolerated doses, or use of ≥4 medications from different classes irrespective of blood pressure – were eligible. Blood pressure was assessed using the mean of in-office automated devices measured three times without the investigator present. Each participant underwent a 1-mg overnight dexamethasone suppression test (DST) with hypercortisolism defined as a post-DST cortisol >1.8 µg/dL with adequate dexamethasone levels (≥140 ng/dL). Key exclusion criteria included white-coat hypertension, nonadherence to antihypertensive medications, systemic glucocorticoid exposure, eGFR <30 mL/min/1.73m², severe untreated sleep apnea, excessive alcohol use, and oral contraceptive use. Participants with hypercortisolism underwent additional evaluation including ACTH, cortisol levels, and non-contrast CT imaging of the adrenal glands. The primary endpoint was the prevalence of hypercortisolism.
Of 1,409 consented participants, 1,131 met eligibility criteria and 1,086 completed the DST. The mean age was 65 years, approximately 51% were female, 57% were White, 37% were Black or African American, and 26% were Hispanic or Latino. The mean systolic blood pressure was 140 mmHg, and participants were on a mean of approximately 4 antihypertensive medications; 59% were enrolled under the elevated SBP criterion and 41% under the ≥4 medications criterion.
The primary endpoint demonstrated that 27.3% of patients with rHTN had hypercortisolism (95% CI: 24.7%–31.1%). Among those with hypercortisolism, the mean post-DST cortisol was 4.2 µg/dL. On CT imaging, approximately 24% of patients with hypercortisolism had adrenal nodules, and 35% had adrenal enlargement.
Notably, there were no significant differences in age, race, ethnicity, blood pressure, or HbA1c. Those with hypercortisolism had a lower BMI (32.0 vs. 33.5 kg/m²; p=0.002) and lower waist circumference (106.9 vs. 109.3 cm; p=0.048), and were more likely to be male (56% vs. 46%; p=0.003). Patients with hypercortisolism also had significantly worse kidney function, with a lower mean eGFR (63.8 vs. 71.9 mL/min/1.73m²; p<0.0001) and a higher median urine albumin-to-creatinine ratio (234.7 vs. 139.9 g/kg; p<0.0001), and were significantly more likely to be in higher CKD progression risk categories (p<0.0001). Among those with eGFR <45, hypercortisolism prevalence was 43.6%. Cardiac disorders including atrial fibrillation (11.4% vs. 9.1%), coronary artery disease (12.8% vs. 9.5%), and heart failure (13.8% vs. 10.3%) were all numerically more common in those with hypercortisolism, though these differences were not statistically significant. Glucose above target (HbA1c ≥6.5%) was also numerically more common with hypercortisolism (40% vs. 34%), and those with hypercortisolism were on significantly more antihyperglycemic medications. Markers of primary hyperaldosteronism were present in 19.9% of all participants and in 21.5% of those with hypercortisolism; 5.9% of the total population demonstrated cortisol-aldosterone co-secretion.
Limitations include the geographic restriction to the United States, a low proportion of Asian participants, lack of differentiation between heart failure subtypes, the cross-sectional design without longitudinal follow-up for cardiovascular events, and the inability to establish causation. However, the prevalence finding of 27.3% is consistent with a prior smaller Brazilian study (26.5%) using similar enrollment criteria.
Deepak L. Bhatt, MD, MPH, MBA, Director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine, concluded: “MOMENTUM is the first, large US-based study in patients with resistant HTN assessing the prevalence of hypercortisolism. Screening for both hypercortisolism and hyperaldosteronism should be considered in patients with resistant hypertension.”