Kyushu University researchers have made a groundbreaking discovery regarding aldosterone-producing adenomas (APAs), which are adrenal gland tumors responsible for high blood pressure. Through the application of advanced analysis techniques, they found that these tumors consist of at least four distinct cell types, including those capable of producing cortisol, the primary stress hormone in the body.
Their findings were published in PNAS during the week starting February 24th and shed light on why some APA patients experience unexpected health issues such as weakened bones. Moreover, these insights pave the way for novel treatment strategies to combat APAs.
Currenly, surgery is the only effective cure for APAs, a method that has remained unchanged over decades. To develop alternative therapies like drugs, it’s crucial to understand how tumors function at a molecular level and how different cell types interact within them.” says Maki Yokomoto-Umakoshi, the study’s first author and an Assistant Professor in the Department of Endocrine and Metabolic Diseases at Kyushu University Hospital.
Aldosterone-producing adenomas (APAs) are non-cancerous tumors that develop on top of the adrenal glands situated above the kidneys. These small glands produce essential hormones, such as aldosterone, cortisol, and sex hormones. Their location makes APAs a major contributor to primary aldosteronism—a condition characterized by excessive production of aldosterone leading to high blood pressure. Primary aldosteronism accounts for about 5-10% of all hypertension cases and is associated with higher risks of heart disease and stroke in patients compared to those with common hypertension.
“Without adequate treatment, these patients may develop severe health problems including cardiovascular diseases, diabetes, and bone weakness,” adds Yokomoto-Umakoshi. “This research provides a clearer understanding of APA composition and could lead to better management of this condition.”
The study focused on APAs caused by changes in the KCNJ5 gene responsible for approximately 40-70% of all these tumors. These mutations are usually associated with larger, earlier-onset tumors that exhibit symptoms not easily attributed to overproduction of aldosterone alone.
To gain deeper insights into APA composition and hormone secretion patterns, a multidisciplinary team led by Professor Yoshihiro Ogawa from Kyushu University collaborated with Osaka University, Kyoto University, and the University of Tokyo. Using advanced techniques for comprehensive analysis in unprecedented detail, they mapped out various cell types within these tumors along with their functions.
The research unveiled that APAs are more complex than initially believed; they contain at least four distinct cell types that start from stress-responsive cells evolving into aldosterone-producing or cortisol-producing cells. The latter then transform into stromal-like cells, aiding tumor growth. Special immune cells known as lipid-associated macrophages were found to be abundant in these tumors with potential roles in hormone production and tumor development.
“These diverse cell types within APAs can impact a patient’s health through various means—more than just hypertension caused by excess aldosterone,” explains Yokomoto-Umakoshi. “Symptoms like bone weakness induced by excessive cortisol are also significant.”
In the future, researchers plan to extend their analysis beyond KCNJ5-mutated APAs and explore other hormone-producing tumors using these advanced techniques. They hope that these findings will serve as a foundation for developing new drug treatments targeting specific aspects of APA biology.
“By better understanding APAs, we open up promising avenues for targeted therapies such as directly addressing lipid-associated macrophages or excess cortisol production,” concludes Yokomoto-Umakoshi. “This research brings us closer to more effective management and treatment options for patients with these tumors.”
