Clinical consequences of hypercortisolism

Hypercortisolism is associated with significant clinical consequences, including morbidity and mortality. When left untreated, classically described overt Cushing syndrome is associated with 50% mortality in as few as 5 years.1 There is a wide spectrum of clinical manifestations at any given level of hypercortisolism.2 Even when clinical signs of classically described overt Cushing syndrome are not present, patients with adrenal adenomas and less severe hypercortisolism showed an increased risk of cardiovascular events and mortality.3 A recent retrospective study showed that the survival rate for all-cause mortality in patients with post-dexamethasone suppression test (DST) cortisol levels ≥1.8 ug/dL was 57% compared with 91.2% in those with post-DST <1.8 ug/dL.4
excess cortisol secretion is linked to lower survival rates

Risk of cardiovascular events

Even when clinical signs of classically described overt Cushing syndrome are not present, patients with adrenal adenomas and less severe hypercortisolism showed an increased risk of cardiovascular events and mortality. A retrospective, single-center study analyzed the risk of cardiovascular events in patients who were grouped based on their post-DST cortisol levels.4

Patient Groups Based on DST Levels4

baseline versus study end DST levels
baseline versus study end DST levels
baseline versus study end DST levels

Incidence of New Cardiovascular Events at End of
Follow-Up4

patients with cardiovascular diseases worsened
DST=overnight dexamethasone suppression test.
The above graph information was gathered during a 15-year, retrospective, single-center study analyzing 198 consecutive patients with adrenal adenomas. Individuals were assessed every 18 to 30 months for the first 5 years. The mean follow-up period was 7.5 years (range: 26 months to 15 years). New cardiovascular events were defined as nonfatal acute myocardial infarction, percutaneous transluminal coronary angioplasty, and surgical bypass for ischemic heart disease, or ischemic stroke, which occurred during the study.

Adenoma size and elevated risk5

In another multicenter study, a correlation was found between the size of adrenal adenomas and the elevated risk of hypercortisolism and cardiovascular events.

The study observed 206 patients with adrenal adenomas over a 5-year period. Baseline cortisol measurements confirmed hypercortisolism in 24 of the patients (DST cortisol >1.8 µg/dL).

At follow-up, patients with an adenoma ≥2.4 cm in size were more likely to develop hypercortisolism over time. An additional 15 patients (8.2%) progressed into hypercortisolism by study end.

Patients with hypercortisolism were found to be at elevated risk of cardiovascular events.

Adenoma Diameter ≥2.4 cm and DST Cortisol >1.8 μg/dL Confer Elevated Risk5

prevalent versus incident cardiovascular events
DST=overnight dexamethasone suppression test.
*An odds ratio (OR) is the measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared with the odds of that outcome occurring in the absence of that exposure.
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Learn more about recent studies that evaluated the risk of cardiovascular events and mortality in patients with hypercortisolism.

Risk of osteoporosis

Excess cortisol promotes bone loss. Hypercortisolism can impact bone mineral density, bone architecture, and bone remodeling, which affects bone strength.6

Burden of disease

Hypercortisolism is associated with persistent physical morbidity. CV risk, fatigue, muscle disease (myopathy), and bone fragility negatively impact well-being and quality of life (QoL).7

Excess cortisol can greatly diminish a patient’s quality of life by aggravating several physical and psychological conditions.

>80%

of patients experience weight gain7

≥70%

experience depression, psychosis, and cognitive dysfunction8

~66%

fulfill at least 3 criteria for metabolic syndrome9

38%-50%

experience osteoporosis10

Time to diagnosis impacts QoL

Predictors for a lowered QoL in patients with hypercortisolism include a delay in getting an accurate diagnosis and the need to see multiple physicians before an accurate diagnosis is made.7

Patient Story

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“It was scary to know that I had a rare disease. ...However, more than anything, I was so relieved to finally know that I wasn’t crazy…”

Read Jenny's Story
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Screening & Diagnosis