Adrenalectomy vs Semaglutide for Autonomous Cortisol Secretion

(IMPACT-MACS Trial)

This trial explores how two treatments—adrenalectomy (surgical removal of an adrenal gland) and semaglutide (a medication for weight management)—affect people with mild autonomous cortisol secretion (MACS). Researchers aim to determine which treatment better improves insulin resistance and how they alter cortisol levels and other health factors like blood pressure and muscle strength. Participants with MACS will either undergo surgery or take semaglutide, while a control group without adrenal issues will also take semaglutide. Ideal candidates are adults with a known adrenal gland issue and mild cortisol imbalance, or those without adrenal issues but with cardiometabolic conditions like high blood pressure.

As an unphased trial, this study provides a unique opportunity to enhance understanding of treatment options for MACS.

The trial requires that your medication doses have been stable for at least 4 weeks before joining. It doesn't specify if you need to stop any current medications, but you should discuss your specific situation with the trial team.

Research shows that semaglutide is generally safe for use. Studies have found it effective for weight loss and other conditions, with a well-established safety record. Some individuals might experience mild side effects like nausea or vomiting, but these are usually manageable.

Adrenalectomy, the surgery to remove an adrenal gland, has been used for a long time. It is a standard treatment for certain conditions, and its safety is well-established.

Researchers are excited about these treatments for managing mild autonomous cortisol secretion (MACS) because they offer distinct approaches. Adrenalectomy, a surgical option, directly removes the adrenal gland, potentially resolving the source of excessive cortisol production. In contrast, semaglutide, a medication typically used for weight management, is being investigated for its ability to regulate cortisol levels without surgery. This drug offers a non-invasive alternative, which might be appealing for those who are not suitable candidates for surgery or prefer a medical approach. The combination of these options could provide more personalized treatment plans based on individual patient needs and responses.

This trial compares the effects of adrenalectomy and semaglutide on individuals with mild autonomous cortisol secretion (MACS). Research has shown that removing an adrenal gland through surgery, known as adrenalectomy, can improve various health outcomes in people with MACS, potentially balancing insulin levels and reducing issues related to cortisol, a stress hormone. Meanwhile, semaglutide, a medication often used for weight loss, has shown promise in helping people lose weight and manage cortisol levels. One study found that using semaglutide with another treatment led to significant weight loss and normalized cortisol levels. This trial studies both treatments to assess their impact on insulin resistance, cortisol patterns, and other health factors in people with MACS. This research offers hope that either option could provide meaningful benefits.¹⁶⁷⁸⁹