Characteristics of preoperative steroid profiles and glucose metabolism in patients with primary aldosteronism developing adrenal insufficiency after adrenalectomy

Abstract

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy. Following surgery, most patients retain normal adrenal function, while some develop adrenal insufficiency (AI). To facilitate early detection and treatment of AI, we aimed to identify variables measured pre-operatively that are associated with post-operative AI. Variables obtained from 66 patients before and after surgery included anthropometrical data, clinical chemistry, endocrine work-up. LC-MS/MS steroid hormone profiles from tests before surgery (ACTH-stimulation, saline infusion, dexamethasone suppression) were obtained. Based on 78 variables, machine-learning methods were used in model fitting for classification and regression to predict ACTH-stimulated cortisol after surgery. Among the 78 variables, insulin concentration during pre-operative oral glucose tolerance test (OGTT) correlated positively, and dexamethasone suppressed glucocorticoids correlated negatively with ACTH-stimulated cortisol after surgery. Inclusion of LC-MS/MS measurements allowed construction of better models associated with the occurrence of AI in the training data, but did not allow reliable prediction in cross-validation. Our results suggest that glucocorticoid co-secretion (low insulin during pre-operative OGTT and insufficient suppression of glucocorticoids following dexamethasone) are correlated with the development of post-operative AI. Addition of steroid profiles improved the accuracy of prediction, but cross validation revealed lack of reliability in the prediction of AI.

Figure 1

Single variables correlating with post-operative stimulated cortisol. Pre-operative insulin at 60 min during oral glucose tolerance test (OGTT) is positively correlated with post-operative stimulated cortisol (A). Pre-operative stimulated cortisol is positively correlated with post-operative stimulated cortisol (B). Pre-operative ACTH test baseline estradiol is negatively correlated with post-operative stimulated cortisol (C). Pre-operative dexamethasone suppressed corticosterone is negatively correlated with post-operative stimulated cortisol (D).

Figure 2

Boxplots of differences between severe AI and adrenal sufficiency groups in individual variable (A–C); the classification of gradient tree boosting model in training data (D,E) and cross validation (F,G). *Represent p value smaller than 0.05, namely significant difference. Boxplot of pre-operative insulin at 60 min during oral glucose tolerance test (OGTT) (A). Boxplot of salivary cortisol at 20:00 (B). Boxplot of dexamethasone suppressed corticosterone (C).

Figure 3

Plot of the true value and predicted value by linear regression model without (A) and with (B) LC–MS/MS in cross validation.

Figure 4

Plot of the true value and predicted value by model-based-boosting model without (A) and with (B) LC–MS/MS in training data. Importance of variables in model-based-boosting model (C). Plot of the true value and predicted value by model-based-boosting model with LC–MS/MS in cross validation (D).