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Clinical consequences of hypercortisolism

Excess cortisol activity can lead to serious health consequences, increasing the risk of type 2 diabetes, hypertension, obesity, and cardiovascular disease.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 have an increased risk of CV events and mortality.3

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Cardiovascular events and mortality

Hypercortisolism is associated with significant clinical consequences, including morbidity and mortality1

  • 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. Mean follow-up period was 7.5 years (range: 26 months to 15 years)
  • Patients were grouped based on their post-dexamethasone suppression test (DST) cortisol levels at baseline and at study end

Patients who were diagnosed with classically described overt Cushing syndrome were excluded from the study.

Related Reading

Cardiovascular events and mortality in patients with adrenal adenomas and excess cortisol secretion

Guido Di Dalmazi, Valentina Vicennati, Silvia Garelli, et al

Read Article Summary >


Worsening cortisol secretion patterns over time1

  • At the end of follow-up, patients with DST ≥1.8 μg/dL, and those with a worsened secretion pattern had a higher incidence of cardiovascular disease (CVD) than patients with DST <1.8 μg/dL
  • Post-DST cortisol levels related to all-cause mortality independently of all other risk factors
Circle graphs depicting cortisol levels in patients with Cushing’s disease based on DST results.
Two pie charts showing data from both baseline and end of study. At baseline, 129 patients had DST <1.8 µg/dL; 59 patients had DST 1.8-5.0 µg/dL; and 10 patients had >5 µg/dL. At the end of the study, 114 patients had DST <1.8 µg/dL; 61 patients had DST 1.8-5.0 µg/dL; 10 patients had >5 µg/dL; and 23 patients had worsened or moved up at least 1 category.
DST=overnight dexamethasone suppression test.

Related Reading

Effects of cortisol levels on mortality rates in patients with adrenal adenomas

Miguel Debono, Mike Bradburn, Matthew Bull, Barney Harrison, Richard J. Ross, John Newell-Price

Read Article Summary >

Patients whose post-DST cortisol levels worsened were 4 times more likely to have a CV event.1

Incidence of new cardiovascular events* at end of follow-up1

Bar graph showing likelihood of cardiovascular event when Cushing’s disease is left untreated Bar chart showing that at the end of follow-up, patients who had DST ≥1.8 µg/dL (n=61) had a higher incidence of cardiovascular diseases (16.7%) than patients with <1.8 µg/dL (n=114; 6.7%). Patients with worsened Cushing disease (n=23) had a 28.4% incidence of cardiovascular disease.

Survival rates for all-cause mortality in patients with adrenal adenomas1

Chart shows survival rate for all-cause mortality in patients with adrenal adenomas based on DST results. Bar chart showing that the survival rates for all-cause mortality in patients with adrenal adenomas was 91.2% for patients with DST <1.8 µg/dL and 57% for patients with ≥1.8 µg/dL.
DST=overnight dexamethasone suppression test.
 *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.

Even when clinical signs of classically described overt Cushing syndrome are not present, patients with adrenal adenomas and less severe hypercortisolism have an increased risk of CV events and mortality.1

Increased risk for cardiovascular disease4

Annual rate of CV events higher in patients with hypercortisolism4

  • Retrospective, multicenter study analyzing 206 patients with adrenal adenomas. Follow-up time of ≥5 years (median: 72.3 months; range: 60 to 186 months)
  • In this study, patients were considered to have hypercortisolism if post-DST cortisol levels were >5 μg/dL, or if they had at least 2 of the following: urinary-free cortisol greater than the upper limit of normal; low adrenocorticotropic hormone (ACTH <10 pg/mL); or post-DST cortisol levels >3 μg/dL

Patients who were diagnosed with classically described overt Cushing syndrome were excluded from the study.

Chart at the beginning of the study showing risk of cardiovascular rates associated with hypercortisolism diagnosis
Bar chart showing that the annual rate of cardiovascular events was 3.1% in patients with hypercortisolism, compared with 1.2% in patients without hypercortisolism.
A chart for “after” the study showing risk of cardiovascular events for patients with untreated hypercortisolism.
Bar chart showing that the rate of cardiovascular events at the end of the follow-up period was 20.5% in patients with hypercortisolism, compared with 8.4% in patients without hypercortisolism.

Rate of cardiovascular events4

  • Patients with hypercortisolism were 2.7 times more likely to experience new CV events during the follow-up period
  • Patients with hypercortisolism at baseline were 3.1 times more likely to have had a previous CV event than those without hypercortisolism at baseline
    • The same analysis showed that patients with type 2 diabetes at baseline were 2 times more likely to have had a previous CV event than those without type 2 diabetes at baseline
  • At the end of follow-up, patients with hypercortisolism had a higher prevalence of arterial hypertension and type 2 diabetes than patients without hypercortisolism

Related Reading

Increased cardiovascular disease risk in patients with hypercortisolism

Valentina Morelli, Giuseppe Reimondo, Roberta Giordano, et al

Read Article Summary >

Adenoma diameter ≥2.4 cm and DST cortisol >1.8 μg/dL confers elevated risk.4

Development of hypercortisolism based on adrenal adenoma size4

Results from study showing patients with existing adrenal adenomas went on to develop hypercortisolism. Bar chart showing that during follow-up, 14.3% of patients with an adrenal adenoma ≥2.4 cm at baseline developed hypercortisolism, while only 3.8% of patients with an adrenal adenomal <2.4 cm developed hypercortisolism.
*Four of the 105 patients (3.8%) without hypercortisolism at baseline and with an adenoma <2.4 cm developed hypercortisolism during follow-up.
†Eleven of the 77 patients (14.3%) without hypercortisolism at baseline and with an adenoma ≥2.4 cm developed hypercortisolism during follow-up.

Adrenal adenoma size ≥2.4 cm associated with increased risk of developing hypercortisolism4

  • Over the study period, 8.2% of patients with adrenal adenomas developed hypercortisolism, the risk being particularly increased in patients with an adenoma size ≥2.4 cm
  • Those with adenomas ≥2.4 had an increased risk of CVD

In patients with an adrenal adenoma ≥2.4 cm, clinical and biochemical follow-up is required due to the potential development of hypercortisolism and its related consequences.4

Related Reading

Increased risk of cardiometabolic comorbidities in patients with adrenal incidentalomas with and without autonomous cortisol secretion

Yasir Elhassan, Fares Alahdab, Alessandro Prete, et al

Read Article Summary >

Risk of osteoporosis

Excess cortisol promotes bone loss. Hypercortisolism can impact bone mineral density, bone architecture, and bone remodeling, which affects bone strength.5

Burden of disease

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

>80%

of patients experience weight gain6

≥70%

experience depression, psychosis, and cognitive dysfunction7

~66%

fulfill at least 3 criteria for metabolic syndrome8

38%‒50%

experience osteoporosis9

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.6

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…”

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