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Neuroendocrinology and Pituitary

ORF35-02 - Cortisol Secretion Following Total Bilateral Adrenalectomy: A Multicenter International Retrospective Cohort Study

Sunday, June 14, 2026
3:35 PM - 3:40 PM CT
Location: Room W187

Context: Total bilateral adrenalectomy (BLA) is an established definitive treatment for severe or refractory hypercortisolism or bilateral pheochromocytomas. BLA is generally assumed to result in lifelong primary adrenal insufficiency (PAI), however, reports of partial adrenal recovery and recurrent hypercortisolism challenge this assumption. The long-term frequency, timing, and clinical context of these outcomes remain poorly characterized.

Objective: To characterize long-term adrenal function following total BLA, including the frequency and timing of recovery of cortisol production and recurrent hypercortisolism, and identify factors associated with these outcomes.

Methods: We conducted a multicenter retrospective cohort study of patients treated with total BLA who had at least one documented cortisol assessment after January 1, 2000. Variables included demographic and clinical characteristics, indication for BLA, duration of follow-up, serial cortisol measurements, and adrenal-function status at the time of cortisol testing. Failed total BLA, defined as hypercortisolism documented within three months post-surgery, was excluded. Adrenal function outcomes were categorized as PAI, transition to normal adrenal function, or to recurrent hypercortisolism, based on longitudinal documentation.

Results: Among 635 patients (median age at BLA: 38 years [IQR 27–52]; 426, 67% women), the most common indication for BLA was hypercortisolism (478, 75%, ACTH-dependent in 370, 58%, ACTH-independent in 85, 13%, and unknown subtype in 23, 4% patients), followed by bilateral pheochromocytoma (129, 20%), and other indications (28, 4%). Median follow-up from BLA to last cortisol assessment was 4.8 years (IQR 1.0-12.3).

Overall, 620 patients (98%) remained in PAI throughout follow-up. A change in adrenal function was observed in 15 patients (2%), including transition to normal adrenal function in 2 (0.3%), and transition to recurrent hypercortisolism in 13 (2%). Among patients whose indication for BLA was hypercortisolism, the cumulative 10-year incidence of recurrent hypercortisolism was 3.3% (95% CI: 1.7%-5.6%), occurring exclusively in patients with ACTH-dependent disease. Age, sex, and surgical expertise were not associated with recurrent hypercortisolism, P>0.05 for all).

In 623 patients with known clinical status of PAI, 546 (88%) had stable clinical course, however 77 (12%) patients reported periods of instability, including 28 (5%) with hospitalizations and adrenal crises. Of 74 patients who died during follow up, 4 (5%) were related to adrenal crisis.

Conclusion: In this large multicenter cohort with extended follow-up, the vast majority of patients undergoing total BLA remained in stable PAI. Recurrent hypercortisolism was documented in 3% of patients with BLA for hypercortisolism, all in patients with ACTH-dependent disease.