Differences in morbidity and mortality between unilateral adrenalectomy for adrenal Cushing’s syndrome and bilateral adrenalectomy for therapy refractory extra-adrenal Cushing’s syndrome

Abstract

Purpose In selected cases of severe Cushing’s syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing’s syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing’s syndrome regarding postoperative outcomes. Methods We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008–2021. Patients with adrenal Cushing’s syndrome due to adenoma were compared with patients with ACTH-dependent Cushing’s syndrome (Cushing’s disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival. Results Of 83 patients with adrenalectomy for hypercortisolism (65.1% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing’s syndrome in 60 patients (72.2%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing’s disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0% vs. 33%; p < 0.001) and delayed recovery (median: 10.2% vs. 79.2%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2% vs. 25.0% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0% vs. 8.3%; p = 0.081). Conclusion While unilateral adrenalectomy for adrenal Cushing’s syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing’s syndrome or Cushing’s disease is a more complicated intervention with a mortality of nearly 10%.

Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France

“…Resection of the primary tumor may not possible in a number of cases such as occult and covert or metastatic ACTH-secreting tumors ( 2 , 4 , 11 , 12 ). Bilateral adrenalectomy has been proposed to control severe and intense CS ( 13-15 ); however, both general anesthesia and surgery are not always feasible or risk free in patients with multiple complications ( 2 , 11 , 12 , 15 , 16 ). For these patients, in agreement with Endocrine Society recommendations, first-line combinations therapy with steroid synthesis inhibitors such as metyrapone and ketoconazole have been shown to control hypercortisolism and are preferred by other teams to avoid lifelong adrenal insufficiency ( 17-21 ).…”