High Cortisol Levels in Subclinical Cushing’s Syndrome Patients Linked to Risk of Metabolic Disease, Study Suggests

Elevated cortisol levels in people with subclinical Cushing’s syndrome appear to increase their likelihood of metabolic disease — a group of factors that raise the risk of heart disease — even though these patients don’t have the typical weight gain seen in overt Cushing’s syndrome, a study suggests.

Results of the study were presented at the 2019 Endocrine Society Annual Meeting in New Orleans, in a poster titled, “Clinical Characteristics and Metabolic Features of Patients with Subclinical Cushing’s Syndrome and Its Correlation with Cortisol Level.”

In Cushing’s syndrome, too much cortisol circulates in the body, leading to weight gain, fat deposits, fragile skin, and stretch marks. When a person has excess cortisol but lacks these symptoms, they are diagnosed with subclinical Cushing’s syndrome. However, the characteristics of subclinical Cushing’s syndrome are less understood, and the lack of these common symptoms makes diagnosis and monitoring more clinically challenging.

Since these patients do not have the typical weight gain of overt Cushing’s syndrome, it is unclear if they are also at higher risk of metabolic disease.

To find out, researchers at Nanjing University Medical School in China evaluated the clinical characteristics and metabolic features of subclinical Cushing’s syndrome to determine how cortisol levels correlate.

They analyzed data from 61 patients with overt Cushing’s syndrome, 45 patients with subclinical Cushing’s syndrome, and 52 patients with non-functioning pituitary adenomas — benign tumors in the pituitary gland that do not produce excess hormones — who were used as controls.

Researchers found no difference in age, gender, and body mass index (BMI; a measure of body fat) between the control group and patients with subclinical Cushing’s syndrome. But compared with subclinical Cushing’s syndrome patients, Cushing’s syndrome was more common in younger people (53 vs. 44 years) and in female patients (68.9% vs. 83.6%).

Interestingly, the prevalence of metabolic risk factors was higher among subclinical Cushing’s syndrome patients than in control patients. Factors such as diabetes mellitus (57.8% vs. 32.7%), hypertension (73.3% vs. 53.8%), and low bone mass (41.2% vs. 19.2%) were all more common in subclinical patients.

No significant differences in the incidence of metabolic disease was observed between subclinical and overt Cushing’s patients, suggesting that patients are at higher risk of heart disease even if they don’t show physical signs of Cushing’s syndrome.

Researchers then examined if these metabolic features had any correlation with the patients’ cortisol levels.

First, they found that both subclinical and overt Cushing’s patients had some sort of deregulation in their cortisol circadian rhythm, which is the body’s 24-hour internal clock.

Cortisol levels normally drop during the night — reaching their lowest level around midnight — and after treatment with dexamethasone. However, cortisol levels instead remained elevated in subclinical Cushing’s syndrome patients. This deregulation in the cortisol cycle was even more prominent in overt Cushing’s patients.

The team then found that cortisol levels in subclinical patients were linked to an increase in metabolic risk factors, including higher blood pressure, elevated glucose levels, and a rise in HbA1c — a marker of diabetes mellitus. 

These results show that patients with subclinical Cushing’s syndrome have an increased prevalence of metabolic risk factors, the researchers concluded, adding that evaluating levels of cortisol may help in treatment decision-making, and selecting patients for conservative management versus surgery.