Adrenocortical Adenoma

Researchers have uncovered a surprising layer of complexity in aldosterone-producing adenomas -- adrenal gland tumors that drive high blood pressure. Using cutting-edge analysis techniques, they discovered that these tumors harbor at least four distinct cell types, including ones that produce cortisol, the body's main stress hormone. Their findings not only explain why some patients with these tumors develop unexpected health issues, like weakened bones, but also pave the way toward new treatment strategies. Kyushu University researchers have uncovered a surprising layer of complexity in aldosterone-producing adenomas (APAs) -- adrenal gland tumors that drive high blood pressure. Using cutting-edge analysis techniques, they discovered that these tumors harbor at least four distinct cell types, including ones that produce cortisol, the body's main stress hormone. Published in the week beginning 24 February in PNAS, their findings not only explain why some patients with APAs develop unexpected health issues, like weakened bones, but also pave the way toward new treatment strategies. "Currently, the only way to cure APAs is through surgery to remove the tumor, and this hasn't changed for decades," says first author of the study, Assistant Professor Maki Yokomoto-Umakoshi, from the Department of Endocrine and Metabolic Diseases at Kyushu University Hospital. "To develop new treatment models, such as drug treatments, we urgently need to understand how these tumors work at the molecular level, and how the different cell types interact with each other." APAs are benign (non-cancerous) tumors that develop on the adrenal glands -- small glands on top of the kidneys that produce important hormones, such as aldosterone, cortisol and sex hormones. Due to their location, APAs are a major cause of primary aldosteronism, a condition in which excessive production of the hormone aldosterone leads to high blood pressure. Primary aldosteronism is responsible for about 5-10% of high blood pressure cases, and patients with APAs have a higher risk of heart and blood vessel problems compared to people with common high blood pressure. "Without proper treatment, patients can develop serious health problems like heart disease, diabetes, and bone weakness," adds Yokomoto-Umakoshi. In this study, the researchers focused on APAs caused by changes in a gene called KCNJ5. This mutation, which accounts for around 40-70% of all cases of these tumors, is typically associated with larger tumors that form at a younger age, as well as more severe symptoms that cannot simply be explained by overproduction of aldosterone. However, the cellular makeup of KCNJ5 tumors, as well as which other hormones the tumors might secrete, has previously proven difficult to study. To gain a deeper understanding of APAs, the research team, led by Professor Yoshihiro Ogawa from Kyushu University and in collaboration with Osaka University, Kyoto University, and the University of Tokyo, applied a combination of advanced techniques, providing the first comprehensive view of APAs in unprecedented detail. The researchers were able to map where different cell types were located within these tumors, and how they work together. Furthermore, the techniques allowed the researchers to reveal diverse genetic variation within different regions of APAs and identify exactly which hormones the tumors were producing. The study revealed that APAs are more complex than previously thought, consisting of at least four distinct cell types. The tumor starts with cells that respond to stress, which can then develop into either cells that make aldosterone, or cells that make cortisol. The cortisol-producing cells can then further develop into stromal-like cells that help the tumor to grow. The researchers also discovered that special immune cells called lipid-associated macrophages were more abundant within the tumor, with a potential role in influencing hormone production and tumor growth. "Overall, these tumors contain diverse hormone-producing cells that can affect patient's health in different ways -- not just through high blood pressure, but also through other symptoms caused by excess cortisol, like bone weakness," explains Yokomoto-Umakoshi. In the future, the researchers plan to use these techniques to extend their analysis to other types of APAs, as well as to other tumors that produce excess hormones. They also hope that their current findings help set the stage for developing future drug treatments for APAs. "Now we understand more about APAs, it opens up promising new treatment strategies, such as directly targeting lipid-associated macrophages or excess cortisol," concludes Yokomoto-Umakoshi.

TAMPA, Fla., Nov. 8, 2024 /PRNewswire/ -- In honor of National Day of Radiology, the Carling Adrenal Center spotlights new radiology techniques for adrenal tumor diagnosis and treatment. These novel procedures allow almost all patients with adrenal tumors to have much smaller operations which are curative in the vast majority of patients. With a focus on adrenal vein sampling (AVS), CT, MRI, and PET scans, the center provides critical diagnostic services for conditions like primary hyperaldosteronism (Conn's syndrome), primary hypercortisolism (Cushing's syndrome), adrenal adenomas, pheochromocytomas, and adrenal cancers. Continue Reading "As the world's highest volume adrenal hospital, our priority is ensuring each patient has access to the most precise and targeted diagnostic options," says Dr. Tobias Carling, founder of the Carling Adrenal Center and one of the most experienced adrenal surgeons globally. "Novel techniques we use for imaging and adrenal vein sampling allow us to tailor treatment to each patient's unique needs, often providing clarity that leads to life-changing decisions." As the world's highest volume adrenal hospital, our priority is ensuring each patient has access to the most precise and targeted diagnostic options. Post this Adrenal Vein Sampling: The Key to Personalized Treatment For patients with primary hyperaldosteronism, AVS is sometimes essential in identifying whether excess aldosterone production originates from one or both adrenal glands. This precision allows doctors to tailor treatment, offering surgery for unilateral cases while recommending medication for bilateral cases. Dr. Karan Patel, a leading specialist in AVS, has made the Carling Adrenal Center one of the highest-volume centers for this procedure worldwide, advancing patient care and treatment precision. "With our extensive experience in AVS, we help ensure that each patient receives the most targeted treatment possible," says Dr. Patel. "For many, AVS is the deciding factor in their care plan." However, AVS may not be necessary for all patients. For instance, younger patients with clear unilateral adrenal masses might proceed with treatment based on imaging alone. By tailoring AVS recommendations to individual cases, the Carling Adrenal Center helps avoid unnecessary procedures and focuses on providing optimal care. The Role of Advanced Imaging in Adrenal Health Beyond AVS, the Carling Adrenal Center utilizes advanced imaging to diagnose and manage adrenal conditions: CT Scans are the initial diagnostic tool, giving insights into the size, density, and shape of adrenal masses. MRI Scans provide enhanced resolution and are ideal for patients with complex cases or contrast allergies. PET Scans identify the metabolic activity of tumors, especially useful for detecting metastases in adrenal cancer and pheochromocytomas. Each of these tools plays a unique role in the diagnostic process, ensuring that patients at the Carling Adrenal Center receive the most accurate assessments and treatment guidance. Adrenal Disorders: From Benign to Life-Threatening The Carling Adrenal Center treats a range of adrenal disorders, from benign adenomas to aggressive cancers and hormone-secreting tumors: Adrenal Adenomas may require no treatment if non-functional but need to be removed if producing cortisol or aldosterone, which can lead to conditions like Cushing's syndrome or primary hyperaldosteronism. Pheochromocytomas are tumors causing hypertension, palpitations, and other symptoms, often identified through MRI and PET scans. Cushing's Syndrome results from excess cortisol production, often due to adrenal tumors. It can lead to weight gain, high blood pressure, and other metabolic issues, making early diagnosis critical. Adrenal Cancer is rare but aggressive, requiring immediate diagnosis and treatment, often guided by CT and PET scan imaging. Celebrating National Day of Radiology: The Importance of Imaging in Adrenal Care National Day of Radiology serves as a reminder of the value of imaging in modern medicine. The Carling Adrenal Center is committed to educating patients about these technologies and the diagnostic advancements in adrenal care, ensuring they receive the best possible outcomes through precise, expert-led imaging. For more information on adrenal imaging and adrenal vein sampling, visit . About the Carling Adrenal Center: Founded by Dr. Tobias Carling, one of the world's leading experts in adrenal gland surgery, the Carling Adrenal Center is a worldwide destination for the surgical treatment of adrenal tumors. Dr. Carling spent nearly 20 years at Yale University, including 7 as the Chief of Endocrine Surgery before leaving in 2020 to open to Carling Adrenal Center, which performs more adrenal operations than any other hospital in the world. | (813) 972-0000 About Hospital for Endocrine Surgery The Hospital for Endocrine Surgery is a campus of HCA Florida South Tampa Hospital focused on compassionate patient care and highly specialized treatment of endocrine tumors. We provide a wide array of services necessary for the diagnosis and surgical treatment of tumors of the thyroid, parathyroid and adrenal glands. Our team includes doctors, surgeons, nurses and technicians who have dedicated their careers to delivering the highest cure rates using the most advanced techniques available. HCA's Hospital for Endocrine Surgery is the nation's highest volume hospital for thyroid, parathyroid, and adrenal tumors and cancers. Media Contact: Julie Canan Director of Marketing, Carling Adrenal Center (941) 468-3002 [email protected] SOURCE Carling Adrenal Center WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Corcept Therapeutics announced Wednesday that its experimental treatment for Cushing’s syndrome missed the primary endpoint in a Phase 3 trial intended to support its FDA submission. While patients with hypertension who received relacorilant in the GRADIENT trial saw statistically significant improvements in mean systolic blood pressure from baseline over 22 weeks, the difference between relacorilant and placebo patients was not statistically significant. Corcept’s stock $CORT was down 7% in premarket trading Thursday. Relacorilant did meet a handful of secondary endpoints in GRADIENT, including hyperglycemia and body weight. Patients in this study had a type of Cushing’s syndrome caused by an adrenal adenoma or adrenal hyperplasia, CEO Joseph Belanoff said during its third-quarter results call with investors. Cushing’s syndrome occurs when there is too much cortisol in the body, putting patients at risk for a range of symptoms from weight gain to high blood pressure. The company previously reported that relacorilant met its primary endpoint in a pivotal study called GRACE, showing that patients who remained on the drug after an initial open-label phase maintained improvements compared to those who got placebo and saw their symptoms worsen, Corcept said. “We’re very confident with submitting an NDA based upon the GRADIENT data, but it’s not just the GRADIENT data,” Corcept’s chief development officer Bill Guyer told investors, according to an AlphaSense transcript. “GRADIENT, from its inception, was always designed to be supportive of GRACE, and GRACE was always going to be our pivotal study. And that’s our agreement with the FDA.” The company also touted that relacorilant was well-tolerated in GRADIENT, with no sign of side effects caused by other Cushing’s treatments, including hypokalemia (low potassium levels), endometrial hypertrophy (thickening of the uterine lining) or related vaginal bleeding, and others. Corcept lost a patent fight with Teva earlier this year over its currently marketed Cushing’s syndrome drug Korlym. On the investor call, Corcept’s endocrinology president Sean Maduck said relacorilant “is going to be even better” than Korlym. “It doesn’t have the off-target progesterone effects that we see with Korlym,” Maduck said.