IPM Take
Cardiology has spent years escalating therapies for hypertension, diabetes and obesity. But some patients may not only need more medication; they may need a different diagnosis. Hypercortisolism is moving from an endocrine niche into cardiometabolic risk discussions because cortisol excess can drive hypertension, hyperglycaemia, central adiposity and vascular risk. The danger is twofold: under-screening leaves patients untreated, while indiscriminate screening risks false positives, confusion and specialist bottlenecks. The answer is not screening everyone. It is building clear, risk-based pathways.
Executive Summary
A HCPLive expert discussion, featuring Deepak Bhatt, Stephen Greene, Martha Gulati and colleagues, focused on barriers to recognising and screening for hypercortisolism in cardiovascular practice. The panel discussed how recent evidence and expert recommendations may influence screening in patients with resistant hypertension and cardiovascular disease.
The discussion reflects a broader shift. Hypercortisolism, also known as Cushing syndrome when clinically established, is caused by excessive cortisol activity. It can contribute to hypertension, central obesity, hyperglycaemia, difficult-to-control type 2 diabetes, muscle weakness, fatigue, mood symptoms and increased cardiovascular risk.
Recent trial signals have raised attention. Corcept Therapeutics reported that MOMENTUM, a US study of patients with resistant hypertension, identified hypercortisolism in 27.3% of screened patients. CATALYST, a study in difficult-to-control type 2 diabetes, reported hypercortisolism in 23.8% of screened participants, with higher prevalence among those also taking multiple blood pressure medications. In the treatment phase of CATALYST, mifepristone improved glycaemic control and weight in patients with difficult-to-control type 2 diabetes and hypercortisolism.
These data are clinically provocative, but policy must move carefully. Screening requires accurate patient selection, appropriate biochemical testing, confirmatory endocrinology evaluation, interpretation of false positives and pseudo-Cushing states, and access to treatment. The Endocrine Society recommends treating cortisol-dependent comorbidities in established Cushing syndrome, but also recommends against cortisol-lowering treatment without an established diagnosis.
The policy message is clear: hypercortisolism should become part of the differential diagnosis in selected cardiometabolic patients, especially those with resistant hypertension or difficult-to-control diabetes. But health systems need protocols, not enthusiasm alone.
Why it matters
- Policymakers and public authorities: Secondary causes of cardiometabolic disease are often missed because care pathways are organised around common disease labels. Resistant hypertension pathways should include endocrine evaluation when clinically appropriate.
- Clinicians and providers: Cardiologists and primary care clinicians do not need to become endocrinologists, but they need clear triggers for suspicion, initial screening pathways and referral criteria.
- Endocrinologists: Broader screening will increase demand for confirmatory testing, interpretation and management. Endocrinology capacity must be part of implementation planning.
- Payers and HTA bodies: Coverage decisions should consider the value of targeted screening in high-risk groups, while avoiding waste from unfocused testing.
- Patients and advocates: Patients with resistant hypertension or difficult-to-control diabetes are often blamed for poor control. Some may have an unrecognised biological driver that requires specialist evaluation.
Resistant hypertension is often treated as a medication problem. Add another drug. Increase the dose. Check adherence. Blame salt. Blame weight. Blame the patient.
Sometimes that is the right clinical path. But sometimes the real problem is that the diagnosis is incomplete.
That is the message behind a new HCPLive expert discussion on hypercortisolism screening in cardiology. The panel focused on how recent clinical evidence and expert recommendations may influence recognition of cortisol excess in patients with resistant hypertension and cardiovascular disease.
This is not a small shift. It asks cardiology to look beyond the usual frame.
Hypertension is common. Type 2 diabetes is common. Obesity is common. Cardiovascular disease is common. Because these conditions are so common, health systems often treat them as routine. But cortisol excess can sit underneath the same clinical picture: high blood pressure, worsening glucose control, visceral adiposity, fatigue, mood symptoms, muscle weakness and elevated cardiovascular risk.
That overlap is exactly why hypercortisolism can be missed.
Classic Cushing syndrome may be recognisable. Milder or less typical hypercortisolism is harder. Patients may not look like textbook cases. They may simply appear to have difficult cardiometabolic disease despite escalating therapy.
Emerging data are now forcing a rethink.
At ACC 2026, Corcept Therapeutics reported results from MOMENTUM, a study that screened 1,086 patients with resistant hypertension across 50 US sites. According to the company, 27.3% had hypercortisolism using a standardised 1-mg dexamethasone suppression test. Corcept also reported that prevalence was 32.6% among patients with HbA1c of at least 7.5% who were taking three or more blood pressure medications.
CATALYST moved the same question into difficult-to-control type 2 diabetes. Published prevalence data reported endogenous hypercortisolism in 23.8% of participants with inadequately controlled type 2 diabetes. ADA later reported treatment-phase results showing that mifepristone reduced HbA1c by 1.5% compared with 0.2% with placebo in patients with difficult-to-control type 2 diabetes and hypercortisolism, with associated weight and waist reductions.
These findings are important, but they must be interpreted carefully.
MOMENTUM data were company-reported and presented at a conference. CATALYST is stronger because prevalence data were published in Diabetes Care, and treatment results were presented and published, but the field still needs longer-term outcomes, independent replication and clear implementation standards.
The worst response would be to ignore the signal.
The second-worst response would be to turn it into uncontrolled screening enthusiasm.
Hypercortisolism testing is not the same as checking a lipid panel. Screening can produce false positives, especially when clinical context is poor. The 1-mg overnight dexamethasone suppression test is a standard approach, but interpretation has caveats. Dexamethasone metabolism, medications, alcohol use, depression, poorly controlled diabetes, pregnancy, kidney failure and other factors can complicate results. Late-night salivary cortisol and urinary free cortisol also require careful collection and interpretation.
A positive screen is not the end of the pathway. It is the beginning.
This is where policy matters.
If cardiology starts screening selected patients for hypercortisolism, health systems need to answer operational questions immediately. Which patients qualify? Resistant hypertension only? Resistant hypertension plus diabetes? Difficult-to-control diabetes plus multiple antihypertensives? Younger patients with severe disease? Patients with adrenal incidentalomas? Patients with classic Cushing features?
Who orders the test? Who explains it? Who follows the result? Who confirms the diagnosis? Who rules out pseudo-Cushing states? Who treats the patient? Who monitors cardiovascular risk during and after endocrine treatment?
Without answers, screening becomes chaos.
This is why the HCPLive discussion is useful. It does not only ask whether cortisol excess matters. It asks how screening could actually be implemented, including clinician education, patient awareness and workflow prompts.
The cardiologist’s role should be suspicion and pathway activation, not solo endocrine diagnosis.
Cardiology is already dealing with a wave of secondary and precision diagnoses: primary aldosteronism, sleep apnoea, chronic kidney disease, familial hypercholesterolaemia, lipoprotein(a), genetic cardiomyopathies, transthyretin amyloid cardiomyopathy, endocrine hypertension and cardio-kidney-metabolic disease. Hypercortisolism belongs in that broader movement.
The common thread is that cardiology is no longer just treating events. It is being asked to identify upstream mechanisms.
That is good medicine. It is also a workforce problem.
Most cardiology clinics are not built to handle endocrine screening pathways. Primary care is under pressure. Endocrinology capacity is limited. Many patients with resistant hypertension already struggle with access, adherence, cost, transport and fragmented follow-up.
Adding a new screening expectation without building infrastructure will fail.
A serious pathway should include three layers.
First, risk-based identification. Screening should target patients where suspicion is justified, such as resistant hypertension, difficult-to-control type 2 diabetes, adrenal incidentaloma, characteristic Cushing features, unexplained hypokalaemia, early severe disease or cardiometabolic disease that remains poorly controlled despite appropriate therapy.
Second, standardised testing and interpretation. Clinicians need simple protocols for initial testing, medication review, timing, repeat testing and referral. Electronic health record prompts could help, but only if they are specific enough to avoid alert fatigue.
Third, specialist confirmation and treatment. Endocrinology should confirm diagnosis and guide management. The Endocrine Society recommends normalising cortisol levels or cortisol action in patients with overt Cushing syndrome and treating cortisol-dependent comorbidities, but it also recommends against treatment without an established diagnosis.
That caution is essential.
The existence of a treatable endocrine cause does not mean every difficult patient has it. It means cardiology should stop assuming that every difficult case is just ordinary hypertension or diabetes.
The treatment landscape also needs honesty.
Mifepristone is FDA-approved to control hyperglycaemia secondary to hypercortisolism in adults with endogenous Cushing syndrome who have type 2 diabetes or glucose intolerance and have failed surgery or are not surgical candidates. It is not approved for ordinary type 2 diabetes unrelated to endogenous Cushing syndrome. Other cortisol-directed therapies and surgery may be relevant depending on cause, severity and patient profile.
Recent regulatory history also shows why caution matters. FDA declined to approve relacorilant for hypertension secondary to hypercortisolism in December 2025, citing the need for additional evidence of effectiveness for a favourable benefit-risk assessment. That does not erase the screening signal, but it reminds policymakers that diagnosis and treatment evidence must be kept separate.
Screening can identify patients. Treatment must still prove benefit.
The policy opportunity is larger than one drug or one company.
Resistant hypertension remains a major cardiovascular risk problem. Difficult-to-control diabetes remains a major cardiometabolic problem. If a meaningful subgroup has unrecognised cortisol excess, then current care pathways are missing a reversible driver of risk. That would make hypercortisolism screening a precision medicine issue, not just an endocrine niche.
But precision medicine must be disciplined.
The goal should not be more testing. The goal should be better targeting.
The right patients should be screened. Positive results should be confirmed. Patients should be referred. Cardiometabolic risk should be managed while the endocrine work-up proceeds. Payers should cover appropriate testing and specialist evaluation. Data systems should monitor who is screened, who is diagnosed, who is treated and whether outcomes improve.
This is how a signal becomes a pathway.
The future of cardiometabolic care will not only be GLP-1s, SGLT2 inhibitors, renal protection and lipid lowering. It will also be identifying the hidden biology behind patients who do not respond as expected.
For some, cortisol may be part of that biology. Cardiology does not need to own hypercortisolism. But it can no longer afford not to look for it.
