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

Xiao Wang,Lisa Sturm,Martin Bidlingmaier,Sonja L Kunz,Daniel A Heinrich,Felix Beuschlein,Olaf Uhl,Nina Heger,Martin Reincke

doi:10.1038/s41598-021-90901-4

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.

Highlights

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy
Our study identified several single features before surgery that significantly correlated with adrenal cortisol production after surgery, and correlated with ACTH stimulated cortisol after surgery in linear regression models
We demonstrated that adding information from steroid profiles determined by LC–MS/MS to conventional laboratory data could improve both, regression with ACTH stimulated cortisol after surgery and accuracy of classification of patients in the adrenal insufficiency (AI) and Adrenal sufficiency (AS) groups in our data

Summary

Introduction

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy. We recently have reported prevalence and clinical characteristics of insufficient glucocorticoid production in a subgroup of APA patients following unilateral adrenalectomy, resulting in transient or even prolonged adrenal insufficiency (AI) and rarely to a life-threatening adrenal crisis. Our hypothesis for the present study was that extending standard biochemical testing by dynamic endocrine tests combined with LC–MS/MS-based steroid profiling would allow us to better characterize the adrenal capacity of the patients, and thereby to predict the individual risk for development of AI following adrenalectomy. Our objectives were (a) to identify variables before surgery that correlate to cortisol production after surgery; (b) to determine the utility of LC–MS/MS steroid profiling before surgery to predict AI after surgery; and (c) to crossvalidate the performance of a prediction model established based on our data

Objectives

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Conclusion