Risk factors for adrenal insufficiency after adrenalectomy for mild autonomous cortisol secretion.

Aggarwal, Akanksha; Balkan, Ali Osman; Sistla, Divya; Mastandrea, Katherine; Dassanaike-Perera, Mikaela; Seethala, Raja R; Leung, Janet H; Yip, Linwah et al. · Surgery · 2026

retrospective_cohort · Level III

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Abstract

Although unilateral adrenalectomy can improve metabolic outcomes associated with mild autonomous cortisol secretion, it can also be associated with postoperative adrenal insufficiency. We aimed to look at the incidence and risk factors of suspected adrenal insufficiency in these patients. Adults undergoing unilateral adrenalectomy for mild autonomous cortisol secretion, defined by cortisol >1.8 μg/dL following 1-mg post-dexamethasone suppression test (post-DST), were included. Patients with adrenocortical carcinoma or Cushing syndrome were excluded. Suspected adrenal insufficiency was defined by a postoperative day 1 morning serum cortisol <10 μg/dL or requirement for glucocorticoid replacement. Predictors of suspected adrenal insufficiency were assessed using multivariable logistic regression. A total of 189 patients were identified: 160 had unilateral and 29 had bilateral disease. Overall, 48% developed suspected adrenal insufficiency (52.5% unilateral vs 24% bilateral). Median age, body mass index, adrenocorticotropic hormone, and dehydroepiandrosterone sulfate levels did not differ between the group that developed suspected adrenal insufficiency and the group that did not. However, the suspected adrenal insufficiency group had higher preoperative 1-mg post-DST cortisol levels: median (interquartile range) 5.5 (3.6-9.4) vs 3.3 (2.4-5.0) μg/dL (P < .01). Among unilateral cases, 65 patients had post-DST cortisol >5 μg/dL, of which 46 (71%) had suspected adrenal insufficiency postoperatively. On multivariable analysis (adjusted for age, sex, and adrenocorticotropic hormone), post-DST cortisol >5 μg/dL was associated with a 4-fold increased risk of glucocorticoid replacement beyond 1 year. Median (interquartile range) glucocorticoid treatment duration was 6 (2.0-20.5) months. Suspected adrenal insufficiency is common after unilateral adrenalectomy for mild autonomous cortisol secretion. Preoperative 1-mg post-DST cortisol is a strong predictor of adrenal insufficiency and should guide postoperative monitoring and clinical suspicion for adrenal insufficiency.