Women with mild autonomous cortisol secretion are at greater risk for cardiometabolic disease

1. In patients with benign adrenal tumors, women are more likely to be diagnosed with mild autonomous cortisol secretion (MACS).

2. Patients with MACS have a higher prevalence and severity of cardiometabolic disease, namely hypertension and type 2 diabetes.

Evidence Rating Level: 2 (Good)

Study Rundown: While benign adrenal tumors are routinely incidentally discovered by imaging, not all these tumors have pathological effects, existing as nonfunctional adrenal tumors (NFAT). However, others overproduce steroids resulting in mild autonomous cortisol secretion (MACS) or Cushing’s syndrome (CS) if severe. The clinical impact of these diseases on cardiometabolic disease is poorly described. This study, therefore, sought to characterize the cardiometabolic disease burden and steroid excretion in this population via a cross-sectional study. Patients with benign adrenal tumors were classified with NFAT, MACS-1 (possible), MACS-2 (definite), or CS based upon clinical assessment and 1-mg overnight dexamethasone suppression test. Results revealed that MACS-2 and CS were more prevalent among women. Compared to patients in the NFAT group, patients with MACS-2 and CS were more likely to have hypertension, require antihypertensives, type 2 diabetes, and require insulin therapy. Taken together, this study supports that women with benign adrenal tumors are more likely to be diagnosed with MACS and are consequently at greater risk for hypertension and type 2 diabetes, warranting regular cardiometabolic assessment for this population. This study was limited by its cross-sectional study design and predefined clinical outcomes biased for cardiometabolic outcomes.

Click to read the study in Annals of Internal Medicine

Relevant Reading: Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis

In-Depth [cross-sectional study]: In this prospective, cross-sectional study, 1305 patients diagnosed with incidental benign adrenal adrenocortical adenoma were selected across 14 participating centers. Patients with other diagnoses of cortisol excess such as primary aldosteronism or on cortisol-altering medications were excluded. Following clinical assessment and 1-mg overnight dexamethasone-suppression, patients were categorized into having a nonfunctional adrenal tumor (NFAT) (morning serum cortisol <50 nmol/L), possible mild autonomous cortisol secretion (MACS-1) (morning serum cortisol: 50-138 nmol/L), definite MACS (MACS-2) (morning serum cortisol: >138 nmol/L), or Cushing’s syndrome (CS) (presence of overt clinical symptoms of CS). The results found that while women made up the majority of the study cohort (67.3%), the proportion of females was more pronounced in the MACS-2 (73.6%) and CS (86.2%) groups. With respect to cardiometabolic disease, patients in the MACS-2 group were more likely to have hypertension (adjusted prevalence ratio [aPR], 1.15; 95% confidence interval [CI], 1.04-1.27), require three or more hypertensives (aPR, 1.31; 95% CI, 1.02-1.68) and requirement for insulin therapy (aPR, 1.89; 95% CI, 1.01 – 3.52) when compared to patients in the NFAT group. The same trend was found with greater significance for those in the CS group. The prevalence of dyslipidemia was not found to be significantly different between all groups. Additionally, these findings were not found to be attributed to other factors such as 1-mg DSG results, the presence of bilateral tumor, or adrenal tumor size. Finally, urinary steroid profiling found that patients with MACS and CS were more likely to have lower excretion levels of androgen metabolites and increased excretion levels of glucocorticoids. Overall, this study supports increased cardiometabolic disease burden amongst women with MACS.

Image: PD

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