Netherlands: Mild autonomous cortisol secretion (MACS) refers to adrenal tumours found incidentally with adrenocorticotropic hormone-independent cortisol hypersecretion without clinical signs of Cushing's syndrome.
Over Cushing's syndrome is known to be associated with cardiometabolic comorbidities and cortisol hypersecretion with increased risk of mortality, but there is no clarity on the association between MACS and these comorbidities, and the causality is disputed.

Researchers in recent research published in the European Journal of Endocrinology have highlighted the relevance of MACS since both cardiometabolic morbidities and mortality appeared to increase in patients with MACS compared to patients with non-functioning incidentalomas. They suggest that due to heterogeneous definitions, selective reporting, various outcomes, and missing data, there is a need to interpret the reported pooled estimates with caution.
The systematic review and meta-analysis revealed a higher prevalence of diabetes (Relative Risk (RR) 1.44), hypertension (RR=1.24), and dyslipidemia (RR=1.23) in patients with MACS.
Iris Pelsma, Departments and Internal Medicine, Division of Endocrinology Leiden University Medical Centre, Leiden, The Netherlands, and colleagues aimed to assess (1) comorbidities associated with, and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; >1.8ug/dL (>50 nmol/l) cortisol level cut-off after the 1mg dexamethasone suppression test) in a systematic review and meta-analysis.
For this purpose, the researchers searched seven databases up to July 2022. Eligible studies were cohort studies, randomized trials, and cross-sectional studies assessing comorbidities potentially attributable to mortality or cortisol excess in patients with adrenal incidentaloma with or without MACS or the effects of surgical or conservative management of MACS. To estimate pooled proportions, a random-effects meta-analysis was performed.
The researchers reported the following findings:
In 30 cross-sectional and 16 cohort studies (n=17,156 patients in total), patients with MACS had a higher prevalence of diabetes (Relative Risk (RR) 1.44), hypertension (RR=1.24), and dyslipidemia (RR=1.23).
All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n=5,921), was increased (HR=1.54).
Nine observational studies (n=856) and two randomized trials (n=107) suggest an improvement in glucometabolic control (RR=7.99, hypertension (RR=8.75 ), and dyslipidemia (RR=3.24) following adrenalectomy.
"Mild autonomous cortisol secretion is associated with multiple cardiometabolic comorbidities, whereas adrenalectomy of the causative adenoma appears beneficial," the researchers wrote.
"The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities," they concluded.
Reference:
Pelsma, I., Fassnacht, M., Tsagarakis, S., Terzolo, M., Tabarin, A., Sahdev, A., Marina, L., Lorenz, K., Bancos, I., Arlt, W., & Dekkers, O. M. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: Systematic review and meta-analysis. European Journal of Endocrinology. https://doi.org/10.1093/ejendo/lvad134