Medical therapy in mild autonomous cortisol secretion

Mild autonomous cortisol secretion (MACS) has an increasing prevalence with age and is associated with cardiometabolic comorbidity and increased mortality. Current guidelines recommend the majority of patients with MACS be managed conservatively, with select people referred for laparoscopic adrenalectomy. There are currently no licensed medications for MACS.

We aimed to systematically review the literature to map out the current available evidence on the use of medical therapy in the treatment of MACS and to assess the research gap. Additionally, we sought to establish the outcome measurements used, to inform the design of future prospective clinical trials.

We searched MEDLINE and EMBASE from conception as well as clinical trial registries to detect all original studies of medical treatments in MACS. Titles and abstracts were screened and full articles reviewed.

A total of 5369 results were found from the search strategy. Thirteen studies met the inclusion criteria, of which 8 were conference abstracts and 5 full-text studies were included in the final analysis. This included 2 studies of metyrapone and 3 studies that used mifepristone. Common outcome measures included blood pressure, glucose measurements, weight, and side effect data.

There is a considerable knowledge gap with regard to the medical management of MACS. Current available evidence consists of a handful of small, heterogeneous studies with a suggestion of a potential benefit in initiating mifepristone or metyrapone in this cohort. Our results highlight the urgent need for larger, prospective studies. To support this, we have provided suggestions for outcome measures.