Asymmetry in adrenal gland volume predicts postoperative adrenal insufficiency in patients with bilateral macronodular adrenal hyperplasia, study shows
Presenter: Kelcie Lushefski, MD, Mayo Clinic, Rochester, MN
Volume of resected adrenal gland predicts development of adrenal insufficiency in patients with bilateral macronodular adrenal hyperplasia (BMAH). Presented April 24, 2026.
In patients with bilateral macronodular adrenal hyperplasia (BMAH), a substantial imbalance in gland volume may predict development of adrenal insufficiency following unilateral adrenalectomy, according to study results presented at AACE 2026.
“Adrenal insufficiency is more likely to develop postoperatively when there is significant asymmetry between sizes of the resected gland versus remnant gland,” study author Kelcie Lushefski, MD, said in an interview.
Postoperative adrenal insufficiency was more common when the resected gland was at least twice the volume of the contralateral gland, according to the analysis of 58 adults who underwent unilateral adrenalectomy at Mayo Clinic.
Marked volume asymmetry, defined as a resected-to-remnant ratio of 2 or greater, was associated with a 74.1% incidence of postoperative adrenal insufficiency, compared with 45.2% among patients not meeting that criterion, according to results of the single-center retrospective analysis.
Treatment implications
The findings could have important implications for management of BMAH, a relatively rare cause of Cushing syndrome.
Management of BMAH has not been extensively studied, the authors noted.
Traditional approaches have included medical therapy and bilateral adrenalectomy. However, both are less than ideal. Medical therapy is often poorly tolerated, while bilateral adrenalectomy causes permanent adrenal insufficiency, Dr. Lushefski said.
By contrast, unilateral adrenalectomy may represent a less aggressive and better tolerated option, according to Dr. Lushefski, particularly in patients with significant asymmetry in the sizes of their glands.
The contralateral gland generally preserves enough function to avoid lifelong steroid replacement; however, temporary adrenal insufficiency remains a known risk.
“In our practice, all patients undergoing unilateral adrenalectomy for bilateral cortisol excess are tested on postoperative day 1 to determine whether adrenal insufficiency is present, and if so, then steroid replacement therapy is initiated,” Dr. Lushefski said.
Criteria for selecting the optimal side for resection in BMAH are not standardized, and data to guide the decision have been limited.
Relevant findings
The Mayo cohort included adults who underwent unilateral adrenalectomy for BMAH between January 1, 2020, and September 1, 2025. Patients were assessed for adrenal insufficiency on postoperative day 1 using morning cortisol or cosyntropin stimulation testing.
Adrenal insufficiency was defined as a morning cortisol level less than 10 µg/dL, or a stimulated cortisol level less than 18 µg/dL after cosyntropin administration. Resected and nonresected adrenal gland volumes were evaluated using portal venous phase computed tomography.
The median age was 61.5 years (range 42–84), and the median body mass index was 32.4 kg/m² (range 19.9–51.1). Forty-four patients (76%) were female.
Postoperative adrenal insufficiency occurred in 34 (59%) of the 58 patients. Among those, 30 patients (88%) recovered during follow-up at a median duration of 2.9 months. At last follow-up, 6 patients (22%) remained on glucocorticoid replacement therapy.
Individual resected and remnant gland volumes were not significantly different between patients who did and did not develop postoperative adrenal insufficiency. Marked asymmetry, however, was associated with a higher incidence of the complication: 20 of 27 patients (74.1%) in that group developed adrenal insufficiency, compared with 14 of 31 patients (45.2%) without marked asymmetry (odds ratio 3.47, P = .034).
Implications for practice
These findings point to a link between gland size and mild autonomous cortisol secretion (MACS) in BMAH, according to Dr. Lushefski.
“MACS in BMAH is associated with adrenal gland size, such that removal of a relatively larger gland, while leaving behind a relatively smaller gland, will more likely result in the development of postoperative adrenal insufficiency,” she explained.
This difference becomes most apparent when there is a volume difference of greater than or equal to 2:1 in gland size, she added.
Counseling patients before surgery is important, given the variability in recovery, Dr. Lushefski added.
“It is important to set clear expectations prior to surgical intervention,” she said. “Although most patients will require only short-term glucocorticoid replacement, some may take longer to recover.”
Disclosures
Dr. Lushefski reported no disclosures in her presentation abstract.
References
Lushefski K, Farsi S, Wang L, et al. Volume of resected adrenal gland predicts development of adrenal insufficiency in patients with bilateral macronodular adrenal hyperplasia (BMAH). Endocrine Pract 2026; 32(suppl). https://doi.org/10.1016/j.eprac.2026.03.011