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Supported by an unrestricted educational grant from Corcept Therapeutics.
Spotlight On
Hypercortisolism in Resistant Hypertension
An underrecognized driver of resistant hypertension, increasingly documented in cardiology patients — distinct from the classic Cushing's syndrome phenotype
Prevalence
10–15 to ~40–49 cases per million person-years 1
Classic Cushing's syndrome (overt form)
27.3% (MOMENTUM, 297/1,086 patients)2,3
Non-classic hypercortisolism — resistant hypertension
23.8% (CATALYST, 252/1,057 patients)4
Non-classic hypercortisolism — difficult-to-control T2D
Age of Onset
Typically during the fourth to fifth decades of life.
ICD-10
E24.9
(Cushing's syndrome, unspecified) — no dedicated code exists for non-classic/mild autonomous cortisol secretion.
There is no established general-population prevalence for non-classic hypercortisolism — it has only been measured within at-risk clinical populations, which is itself part of the story: this isn't found by general screening, it's found by screening the patients already in front of you who aren't responding to standard treatment.
5 Facts you should know
FACT
Non-classic, mild hypercortisolism is increasingly recognized in common cardiometabolic conditions and looks nothing like the overt phenotype of classic Cushing's syndrome (moon face, striae, buffalo hump), which means it can be missed using classic diagnostic criteria alone
FACT
Patients with hypercortisolism-driven hypertension often present first to cardiology for resistant or difficult-to-control blood pressure, without any visible Cushingoid features
FACT
MOMENTUM, a large U.S. study of 1,086 adults with resistant hypertension, found endogenous hypercortisolism in 27.3% of patients using the 1-mg overnight dexamethasone suppression test (DST)
FACT
Excess cortisol raises blood pressure through several concurrent mechanisms, including mineralocorticoid receptor activation, renal sodium retention, upregulation of angiotensin II type 1 receptors, and impaired nitric oxide signaling
FACT
5
The 1-mg overnight DST — one bedtime dose of dexamethasone, one morning cortisol level — is the standard first-step screening test and can be ordered without a specialist referral
Interest over time
Google searches
Common signs & symptoms
Resistant hypertension
Blood pressure uncontrolled despite three or more antihypertensive agents, including a diuretic
No visible Cushingoid features
non-classic hypercortisolism frequently presents without moon face, striae, or buffalo hump
Comorbid difficult-to-control glucose
Prevalence is elevated in patients managing both resistant hypertension and difficult-to-control type 2 diabetes
Screening & Diagnosis
1-mg overnight DST
one bedtime dexamethasone dose, one morning cortisol level — you can order this directly, no referral needed to start
Positive threshold
Post-DST cortisol above 1.8 µg/dL
A positive result is a screen, not a diagnosis
it's your referral trigger, not a treatment decision point
Management Approach
A positive screen is a clear, concrete reason to refer to endocrinology for confirmatory testing
You are not expected to interpret borderline results or manage etiology — that's the referral's purpose
Continue managing hypertension and glucose control in parallel while the referral is pending
Clinical trials
| Title | Description | Phases | Status | Interventions | More Information |
|---|---|---|---|---|---|
| Study of the Prevalence of Endogenous Hypercortisolism in Patients With Resistant Hypertension (MOMENTUM) | This is a non-interventional study to assess the prevalence of endogenous hypercortisolism (eHC) in patients with resistant hypertension (rHTN) and will enroll approximately 1000 patients at approximately 45 sites in the United States (US). Each patient will have an initial visit for screening. Aft... | N/A | Completed | More Info | |
| Study to Determine the Prevalence of Hypercortisolism in Patients With Type 2 Diabetes and Treatment With Korlym® (Mifepristone) (CATALYST) | This is a Phase 4 study with 2 parts: Part 1 (Prevalence Phase) is non-interventional and will assess the prevalence of hypercortisolism in a population with difficult to control type 2 diabetes (T2D) (hemoglobin A1c ≥7.5%) despite receiving standard-of-care therapies. Part 2 (Treatment Phase) is a... | Phase 4 | Completed | Drug: Mifepristone 300 MG [Korlym] Drug: Placebo for mifepristone | More Info |
| A Study to Evaluate the Safety and PK of CRN04894 for the Treatment of Cushing's Syndrome | A Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with CRN04894 (an adrenocorticotropic hormone \[ACTH\] receptor antagonist) in participants with ACTH-dep... | Phase 1, Phase 2 | Recruiting | Drug: atumelnant | More Info |
| A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement | The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach). The investigators are also evaluating new biomarker steroids... | Recruiting | Drug: Osilodrostat | More Info | |
| Combination Osilodrostat and Cabergoline in Cushing's Disease | Cushing disease remains a challenging endocrine disorder in which persistent or recurrent hypercortisolism often requires medical therapy after surgery or when surgery is not feasible. Combination medical therapy has emerged as a rational strategy to improve biochemical control through complementary... | Phase 4 | Enrolling by invitation | Drug: osilodrostat Drug: osilodrostat and cabergoline | More Info |
| Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS) | To characterize the impact of Isturisa on clinical features and comorbidities associated with MACS. The investigators hypothesize that patients treated with Isturisa will exhibit significantly better metabolic indicators (such as fasting glucose, HbA1c, and lipid profile), blood pressure, weight, bo... | Phase 4 | Recruiting | Drug: Osilodrostat (Isturisa) | More Info |
| Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome | This is an open-label extension study to evaluate the long-term safety of relacorilant in patients with endogenous Cushing syndrome who successfully completed participation in a Corcept-sponsored study of relacorilant and may benefit from continuing treatment. | Phase 2 | Active | Drug: relacorilant | More Info |
| Effect of Metyrapone on Cardiovascular Risk Factors in Patients With Adrenal Incidentalomas and Cushing's Syndrome | Drug interventional, controlled, randomized open-label, parallel-group, multicenter study in patients with bilateral adrenal incidentalomas associated with subclinical Cushing's syndrome | Phase 4 | Recruiting | Drug: Metarapone Drug: Standardized antihypertensive therapy | More Info |
| Metyrapone for Mild Autonomous Cortisol Secretion (MACS) | The purpose of this study is to find out whether the study drug, metyrapone, is safe and effective in treating participants with Mild Autonomous Cortisol Secretion (MACS). | Phase 2 | Active | Drug: Metyrapone | More Info |
| Desmopressin Stimulation Test Performance in ACTH-Dependent Cushing Syndrome | Background: Cushing syndrome (CS) is a set of diseases that develop when the body produces too much adrenocorticotropic hormone (ACTH). ACTH stimulates the production of a hormone called cortisol. Excess cortisol can cause serious issues, such as diabetes, high blood pressure, weight gain, and mood... | Phase 2 | Recruiting | Drug: Desmopressin Drug: Dexamethasone | More Info |
| Diagnostic Value of CXCR4-targeted PET/CT in ACTH-dependent and Independent Cushing's Syndrome | In previous clinical practice, 68Ga-Pentixafor PET/CT has demonstrated promising diagnostic utility in various neuroendocrine tumors by targeting CXCR4, a chemokine receptor overexpressed in several ACTH-secreting neoplasms. Building on this, and leveraging the Nuclear Medicine expertise at Peking U... | Phase 1, Phase 2 | Recruiting | Drug: 68Ga-Pentixafor | More Info |
| Long-Term Follow-Up of Survivors of Pediatric Cushing Disease | Background: The pituitary gland produces hormones. A tumor in this gland can cause it to produce too much of the hormone cortisol. Too much cortisol in the body causes Cushing disease. This disease causes many problems. Some of these problems might persist after the disease is cured. Objective: T... | Recruiting | More Info |