Surgery offers best cortisol control for adrenal Cushing’s syndrome
Study: Normalizing levels of hormone key to heart health in these patients
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Among adults with Cushing’s syndrome caused by tumors in both adrenal glands, surgery to remove the tumors led to the best cortisol control and the most favorable outcomes, according to a large international study.
However, the risk of death and the rates of cardiovascular events were similar across different treatment modalities, including surgically removing one or both of the adrenal tumors, cortisol-lowering medications, and symptom management.
Notably, patients who achieved complete biochemical remission, regardless of treatment, experienced fewer cardiovascular events. As such, researchers stressed that “any intervention should aim at normalising — not just lowering — excess cortisol concentrations.”
The study, “Effect of surgical versus conservative management on cardiovascular outcomes in patients with bilateral adrenal tumours and cortisol excess: an international, retrospective cohort study,” was published in the Lancet Diabetes and Endocrinology.
Excess cortisol drives disorders that increase risk of heart disease
Cushing’s syndrome is caused by prolonged exposure to high blood levels of the hormone cortisol, often due to tumors in the adrenal gland or, in the case of Cushing’s disease, the pituitary gland. Cortisol excess can drive metabolic disorders like obesity, diabetes, and high blood pressure, which collectively increase the risk of cardiovascular events such as heart disease and stroke.
A bilateral adrenalectomy, a surgical procedure to remove the cortisol-producing tumors from both adrenal glands, has been traditionally recommended for adrenal Cushing’s syndrome.
Even so, adrenal insufficiency, a serious and potentially life-threatening condition marked by too little cortisol, is a complication of this procedure. Instead, some studies suggest that a unilateral adrenalectomy, or the removal of one adrenal tumor, may reduce cortisol and improve cardiometabolic outcomes compared with managing symptoms alone.
To date, there isn’t a single standard treatment for adrenal Cushing’s, partly because of a lack of data comparing the effects of different therapies on cardiovascular outcomes.
To address this limitation, an international team of researchers across 13 countries evaluated outcomes in adults with bilateral adrenal tumours and cortisol excess by treatment strategy.
“To our knowledge, this is the first international and largest study to date investigating patients with bilateral adrenal tumours and cortisol excess,” the team noted.
Biochemical remission associated with fewer cardiovascular events
The researchers collected data from 105 adults with Cushing’s syndrome and 524 with mild autonomous cortisol secretion (MACS), a condition where adrenal tumors produce slightly too much cortisol, but without the apparent symptoms of full-blown Cushing’s syndrome. Women comprised more than half (68%) of the study’s population.
Metabolic conditions were common in both groups, with higher proportions of high blood pressure and type 2 diabetes among those with Cushing’s syndrome, and higher rates of altered blood fats in MACS patients.
The preferred first-line treatment for Cushing’s syndrome was a unilateral adrenalectomy (47%), followed by a bilateral adrenalectomy (24%). Among those with MACS, most (73%) received non-specific symptomatic therapy, followed by unilateral adrenalectomy (15%). During a median follow-up of 6.8 years, the same proportion of patients in both groups died (7%).
According to the data, there was no clear advantage of surgery, either unilateral or bilateral adrenalectomy, over conservative treatment in terms of all-cause mortality (death by any cause) or cardiovascular events.
However, those who achieved biochemical remission or cortisol control — regardless of treatment — experienced fewer cardiovascular events than those with uncontrolled cortisol.
Overall, biochemical remission rates were low, achieved in less than half (45%) of the adults with Cushing’s syndrome and in about 1 in 8 (13%) of those with MACS.
Our findings clearly indicate that any therapeutic intervention should aim at normalising, not just lowering, cortisol concentrations.
In addition to older age and previous cardiovascular events, smoking was identified as a key risk factor associated with death and cardiovascular events. The researchers noted that a high proportion of study participants were former or current smokers (69%).
Regarding surgical outcomes, all Cushing’s syndrome patients who underwent bilateral adrenalectomy achieved biochemical remission alongside a significant reduction in blood pressure. Among them, less than half (40%) experienced a nonfatal adrenal crisis, or severe cortisol deficiency.
In contrast, a unilateral adrenalectomy led to variable biochemical outcomes in both groups, with no meaningful improvement in cardiometabolic complications. Similar mixed outcomes were seen in a small number of patients who received steroidogenesis inhibitors, or medications that reduce the production of cortisol.
Finally, MACS patients given non-specific symptomatic therapies had a higher risk of cardiometabolic complications and death.
“Our findings clearly indicate that any therapeutic intervention should aim at normalising, not just lowering, cortisol concentrations,” the researchers wrote. “Effective management of [co-existing conditions], such as type 2 diabetes, and support for smoking cessation are crucial for improving outcomes.”
