Predicting postoperative hypocortisolism in patients with non-aldosterone-producing adrenocortical adenoma: a retrospective single-centre study
Authors: Bonaventura I. , Tomaselli A. , Angelini F. , Ferrari D. , De Alcubierre D. , Hasenmajer V. , Sbardella E. , Cozzolino A. , Paganini A. M. , Isidori A. M. , Minnetti M. , Pofi R. 
Published: February 2024

Abstract
Background
Limited information exists on postoperative hypocortisolism and hypothalamus–pituitary–adrenal axis recovery in patients with adrenal incidentaloma following unilateral adrenalectomy. We evaluated frequency of postoperative hypocortisolism and predictors for recovery in non-aldosterone-producing adrenocortical adenoma patients after unilateral adrenalectomy.

Methods
A retrospective analysis of 32 adrenal incidentaloma patients originally included in the ITACA trial (NCT04127552) with confirmed non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy from September 2019 to April 2023 was conducted. Preoperative assessments included adrenal MRI, anthropometrics, evaluation of comorbidities, adrenal function assessed via ACTH, urinary free cortisol, and 1 mg dexamethasone suppression test. ACTH and serum cortisol or Short Synacthen test were performed within 6 days, 6 weeks, 6 months, and a year after surgery.

Results
Six days postoperative, 18.8% of patients had normal adrenal function. Among those with postoperative hypocortisolism, 53.8% recovered by 6 weeks. Patients with earlier adrenal recovery (6 weeks) had lower preoperative 1 mg dexamethasone suppression test (median 1 mg dexamethasone suppression test 76.2 [61.8–111.0] nmol/L vs 260.0 [113.0–288.5] nmol/L, p < 0.001). Univariate analysis showed preoperative 1 mg dexamethasone suppression test negatively related with baseline ACTH levels (r = − 0.376; p = 0.041) and negatively associated with the 6-week baseline (r = − 0.395, p = 0.034) and 30-min cortisol levels during Short Synacthen test (r = − 0.534, p = 0.023). Logistic regression analysis demonstrated preoperative 1 mg dexamethasone suppression test as the only biochemical predictor for 6-week adrenal recovery: ROC curve identified a 1 mg dexamethasone suppression test threshold of 131 nmol/L predicting 6-week recovery with 89.5% sensitivity and 72.7% specificity (AUC 0.87; 95% CI 66.9–98.7, p < 0.001). Other preoperative assessments (tumor size, ACTH levels and anthropometrics) were not associated with postoperative hypothalamus–pituitary–adrenal axis function, but the presence of diabetes was associated with a lower probability of recovery (OR = 24.55, p = 0.036). ACTH levels increased postoperatively in all patients but did not predict hypothalamus–pituitary–adrenal axis recovery.

Conclusions
The preoperative 1 mg dexamethasone suppression test cortisol value and presence of diabetes are the only relevant predictor of hypothalamus–pituitary–adrenal axis recovery in patients with non-aldosterone- producing adrenocortical adenoma undergoing surgery, regardless other clinical and biochemical variables. Notably, pre- and postoperative ACTH levels did not predict hypothalamus–pituitary–adrenal axis recovery. These findings point towards the potential for saving resources by optimizing their allocation during follow-up assessments for patients with non-aldosterone-producing adrenocortical adenoma undergoing unilateral adrenalectomy.