Associations of age, BMI, and renal function to cortisol after dexamethasone suppression in patients with adrenal incidentalomas

INTRODUCTION: The specificity of cortisol after 1 mg dexamethasone (cortisol(DST)) ≥50 nmol/L as a criterion for mild autonomous cortisol secretion (MACS) is approximately 85% in patients with adrenal incidentalomas (AI). The aim was to study the associations of cortisol(DST) to age, BMI, and renal function. METHODS: We studied 1,129 patients with AI examined from 2005 to 2015 at Skåne University Hospital and Helsingborg Hospital. The covariates studied were gender, age, BMI, estimated glomerular filtration rate (eGFR), treatment with inhalation steroids, size of the AI, and size of the smallest AI in patients with bilateral AI (set to 0 in unilateral AI). We used machine learning models to uncover potential nonlinear associations. They were trained to fit the data and examined using feature importance analysis and partial dependence plots. Partial dependence plots show the marginal effect on cortisol(DST) of a covariate averaging over other covariates. RESULTS: Cortisol(DST) was strongly associated with the size of the AI and weakly associated with age, BMI, and eGFR according to the feature importance analysis. The partial dependence plots indicated relatively linear relationships for cortisol(DST) to age (positively) and eGFR (negatively). The association between cortisol(DST) and BMI was nonlinear. At BMI below 30 kg/m(2), cortisol(DST) was negatively associated with BMI, but it was unchanged at higher BMI levels. Using linear regression, we found that cortisol(DST) increased by 11% (95% CI, 7%–14%) for each 10-year increase in age. In patients with a BMI below 30 kg/m(2), cortisol(DST) increased by 23% (95% CI, 16%–31%) for each 5 kg/m(2) decrease in BMI. We found no association at BMI levels above 30 kg/m(2). Cortisol(DST) increased by 9% (95% CI, 6%–11%) for each 10 ml/min/1.73m(2) decrease in eGFR. CONCLUSIONS: Cortisol(DST) is positively associated with age, negatively with BMI if below 30 kg/m(2), and negatively with eGFR. These associations should be considered before diagnosing MACS.