TOPLINE:

In patients with cortisol-secreting bilateral adrenal tumors, bilateral surgical intervention achieved better biochemical control and comorbidity outcomes than unilateral adrenalectomy or medical management, despite similar mortality rates.

METHODOLOGY:

• Bilateral adrenal tumors are a clinically challenging condition that may present as overt Cushing syndrome or mild autonomous cortisol secretion (MACS), are associated with increased risks for cardiometabolic morbidity and mortality if untreated, and currently lack standardized treatment protocols.
• Researchers conducted a retrospective, international cohort study of 629 patients (median age, 62 years; 68% women) diagnosed between January 1, 2000, and January 31, 2022, with bilateral adrenal tumors of ≥ 10 mm and postdexamethasone serum cortisol levels of ≥ 50 nmol/L to evaluate mid-term and long-term clinical and biochemical outcomes by treatment strategy and diagnosis.
• The cohort consisted of 105 patients with Cushing syndrome and 524 patients with MACS; most patients with Cushing syndrome underwent surgery (81%), whereas most with MACS received nonspecific symptomatic treatment (73%).
• Primary endpoints encompassed all-cause mortality and clinical and biochemical remission rates; secondary endpoints were cardiovascular event incidence, prevalence of vascular and metabolic comorbidities, and adrenal crisis incidence.
• Patients had at least 36 months of clinical follow-up with available data on vital status, cardiovascular events, and adrenal crises.

TAKEAWAY:

• After a median follow-up duration of 8.1 years for patients with Cushing syndrome and 6.5 years for those with MACS, 7% of patients in each group had died; active smoking emerged as a key modifiable risk factor for mortality (hazard ratio [HR], 2.18; P = .030).
• In patients with MACS receiving nonspecific symptomatic treatment, increased baseline postdexamethasone cortisol levels were associated with an increased risk for mortality.
• Biochemical remission was achieved in 45% of patients with Cushing syndrome and 13% of those with MACS over a median follow-up duration of 6.8 years.
• Patients with Cushing syndrome or MACS who underwent bilateral adrenalectomy achieved complete biochemical remission, experienced improved arterial hypertension and no fatal adrenal crises, but showed no reduction in the risk for mortality or cardiovascular events; unilateral adrenalectomy and steroidogenesis inhibitor therapy yielded heterogeneous biochemical outcomes.
• Notably, 12% of patients with Cushing syndrome and 16% of those with MACS had at least one cardiovascular event after diagnosis, without substantial differences across treatments; smoking was a risk factor for new-onset cardiovascular events (HR, 1.8; P = .021).

IN PRACTICE:

“Current guidelines, while cautious, likely overestimate the surgical risks of bilateral adrenalectomy (including the risk of adrenal crisis) while underestimating the risk of uncontrolled hypercortisolism. More liberal use of bilateral adrenalectomy should therefore be recommended for patients with bilateral adrenal tumors and hypercortisolism to achieve biochemical remission,” experts wrote in an accompanying editorial.

SOURCE:

This study was led by Elisabeth Nowak, MD, Ludwig Maximilian University Hospital in Munich, Germany. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The follow-up duration may have been insufficient to detect differences in cardiovascular events and mortality. The retrospective design introduced potential imprecisions in classifying Cushing syndrome and MACS. Although all patients received standard medical care and specialized endocrine management, available data did not permit assessment of adherence to individual nonspecific symptomatic therapies.

DISCLOSURES:

This study received no direct funding. Some authors declared research contracts or grants to their institutions, consulting fees, participation on advisory boards, speakers’ honoraria and travel support, roles as clinical investigators, and leadership positions in professional societies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.