ADRENAL INCIDENTALOMAS

Patients with bilateral adrenal incidentalomas appear more likely to have subclinical Cushing syndrome compared with those with unilateral incidentalomas, but surgery may not be the best approach to management, according to a study published onlineJuly 22 in JAMA Surgery.

Although evidence suggests subclinical Cushing syndrome is undertreated and the laparoscopic resection of unilateral lesions improved outcomes in a previous study, "patients with bilateral lesions are more complex because the laterality of cortisol hypersecretion must be determined before surgical intervention," write Jesse D. Pasternak, MD, from the University of California, San Francisco, and colleagues. Given the lack of long-term outcomes data for resection in bilateral patients, surgeons must consider the morbidity risk for adrenalectomy in these patients, which is estimated to be as high as 18% for bilateral adrenalectomy, the authors write.

The researchers retrospectively analyzed a cohort of 500 patients with adrenal disease referred to an academic multidisciplinary adrenal conference at a university hospital between July 2009 and July 2014. Only two of the 135 patients with incidentalomas, both unilateral, had adrenocortical carcinoma. Among the 23 patients (17%) with bilateral incidentalomas, average age was 58.7 years. Lesions on the right side had a mean size of 2.4 cm, which was similar to the mean size of 2.8 cm on the left.

Subclinical Cushing syndrome occurred in five (21.7%) of those patients with bilateral incidentalomas, including most of the seven (30.4%) bilateral patients with hormonal hypersecretion, compared with seven (6.2%) of the 112 patients with unilateral incidentalomas (P = .009). Among the patients with bilateral lesions and subclinical Cushing syndrome, none had diabetes, two had hypertension, and two were obese. Mean follow-up for these patients, which is still ongoing, is 4.6 years.

Meanwhile, 4.3% of the bilateral patients had pheochromocytoma compared with 19.6% of unilateral patients (P = .003). Hyperaldosteronism prevalence was similar across both patients, at 4.3% in bilateral and 5.4% in unilateral patients. Only one patient with bilateral lesions, the patient with pheochromocytoma, underwent a unilateral resection.

"The management of patients with bilateral incidentalomas presents a clinical challenge and is optimized with a multidisciplinary and experienced approach that is highlighted beautifully in this high-volume tertiary-center study," write Linwah Yip, MD, and Sally E. Carty, MD, from the University of Pittsburgh in Pennsylvania, in an accompanying commentary.

"[T]he results suggest that...a benign course is the rule and that mild hypercortisolism does not progress discernibly."

Dr Yip and Dr Carty note that the imprecise thresholds used to define autonomous hypercortisol production and poorly defined outcome measures have prevented clear understanding of patients with asymptomatic hypercortisolism.

"The study results thus also emphasize that better quality data for patients with subclinical Cushing syndrome will be essential to guide future management algorithms, including indications for surgery when both adrenals are incidentally abnormal on imaging," they write.

The complexity and nuance required in evaluating patients with bilateral lesions means surgery is not always indicated, regardless of evidence of hormonal hypersecretion.

"A multidisciplinary approach can help us appropriately identify those patients who do require an adrenalectomy, and the findings of this report exemplify objectively that restraint can often be the better part of valor," Dr Yip and Dr Carty conclude.

The authors and commentators have disclosed no relevant financial relationships.

JAMA Surg. Published online July 22, 2015. Article abstract, Commentary extract