Symptoms Linked With Cardiovascular Risk More Prevalent in Subclinical Cushing’s, Review Finds

Symptoms associated with the risk of heart disease or stroke are common in people with asymptomatic tumors of the adrenal glands – called adrenal incidentalomas – particularly those that produce excess cortisol, a review of studies found.

Problems such as high blood pressure, impaired blood sugar regulation, abnormal lipid (fats) levels, and increased body weight were more prevalent in people with subclinical Cushing’s syndrome than in patients whose tumors were hormonally inactive, the review found.

Given these findings, the researchers made recommendations regarding treatment — including potential surgery — and follow-up approaches, many focusing on lifestyle changes, for each patient group.

The study, “Nonfunctioning and Subclinical Cortisol Secreting Adrenal Incidentalomas and their Association with Metabolic Syndrome: A Systematic Review,” was published in the Indian Journal of Endocrinology and Metabolism.

Adrenal incidentalomas (AIs) are asymptomatic tumors of the adrenal glands, which are located above the kidneys, that may or may not produce excessive cortisol. These tumors usually are discovered by accident during radiologic examination for other problems — hence the name incidentaloma.

Several studies have associated this type of tumor with symptoms of metabolic syndrome, including high blood pressure, abnormal amounts of lipids, or fats, in the blood, obesity, and dysregulation of blood sugar (glucose). All of these can raise the risk of cardiovascular disease, including heart attack or stroke.

Especially for AIs considered nonfunctional — those unable to secrete hormones like cortisol — the relationship with metabolic symptoms is less obvious and not well-understood. As such, long-term outcomes for these patients and best care practices remain controversial.

To collect the available knowledge about AIs and metabolic syndrome, researchers now conducted a literature search for publications on the topic. After screening for the most relevant studies, they selected a total of 18 reports for the final analysis, including 10 retrospective studies, five prospective, two cross-sectional, and one randomized controlled trial.

The studies were published between 2002 and 2017 and involved a total of 1,772 patients with AIs and the results of at least 12 months of follow-up. Among the participants, 58% had nonfunctioning AIs, and 28% had subclinical Cushing’s syndrome — excess cortisol without symptoms of Cushing’s syndrome. Most of the reports came from European countries.

The following systematic review revealed that high blood pressure, impaired blood glucose regulation, abnormal lipid levels, and increased weight — defined by increased body mass index, or BMI — were more common in people with subclinical AIs than in those with nonfunctioning AIs.

In individuals with subclinical disease, the prevalence of abnormal sugar metabolism ranged from 16.6% to 90%, high blood pressure from 33% to 85%, high BMI from 25% to 80%, and abnormal lipid levels from 9% to 90%.

In comparison, these symptoms were less common among patients with nonfunctioning AIs. Among those individuals, 9% to 27% had abnormal glucose metabolism, 24% to 86% had high blood pressure, 27% to 63% had high BMI, and 5% to 60% had abnormal lipid levels.

Surgery to remove the affected adrenal gland, called an adrenalectomy, was beneficial for patients with subclinical, cortisol-secreting tumors. In these people, the surgery helped reduce blood pressure and obesity, and improved control of blood sugar.

However, it did not reduce the risk of cardiovascular disease for those people with nonfunctioning AIs.

The findings support an “increased prevalence of components of metabolic syndrome in patients with subclinical cortisol secreting and nonfunctioning AIs,” the researchers said.

Adrenalectomy may be considered for patients with subclinical Cushing’s syndrome with mild levels of cortisol when medical treatments fail and there is a worsening of cardiovascular risk.

People with these conditions who cannot receive surgery “should be followed up clinically to detect, treat, and control cardiovascular risk factors,” the researchers said.

Surgery is not recommended for those with nonfunctional AIs who do not have high cortisol levels as this is “an area requiring further research,” the team said.

Instead, these patients should undergo detailed endocrine workups to identify those at high cardiometabolic risk. If needed, lifestyle changes and medical treatment should be advised for these patients, the investigators said.

The researchers also stressed that the available evidence to guide treatment decisions is still low, consisting of studies that are potentially biased and have limited reliability.

Given the increasing prevalence of subclinical cortisol-secreting and nonfunctioning AIs and their associated cardiometabolic complications, “there is a clear need for further studies and randomized controlled trials to guide future recommendations for therapy,” the researchers said.