The human body has two adrenal glands, one atop each kidney as illustrated in the drawing above. These tiny organs produce hormones that help the body function correctly and are vital for immune system and stress response. The adrenal glands can often do their job even if they develop a tumor. Mostly the tumors are noncancerous and benign, but some are cancerous, or can cause other serious health problems. Adrenal cancer, although rare, has poor five-year survival rates: around 50% – 60% if removed early and only 10% – 20% if metastasized.

In a recent publication in The Lancet Diabetes & Endocrinology, a team of international researchers describes the epidemiology of adrenal tumors in Olmsted County, Minnesota. They used the Rochester Epidemiology Project, a medical research collaboration that allows population-based research on a level not possible anywhere else in the U.S. Based on those data, the authors recommend that all tumors, even those found secondary to the patient's main health concern, be fully evaluated for malignancy or contributions to hormone imbalance.

History of Endocrine Excellence

In the course of pursuing a doctoral degree at Aarhus University in Denmark, Andreas Ebbehøj, M.D., the study's first author, came to Mayo Clinic as a research trainee, specifically to study this topic.

"International collaboration is key in research, especially in the world of adrenal research," he says. "And what place could possibly be better to go than the birthplace of cortisone, discovered by Drs. Philip Hench and Edward Kendall; the home of living adrenal legends, such as Dr. William Young*; and last but definitely not least, the rising star and co-author of recent adrenal guidelines, Dr. Irina Bancos."

Pictured from left, Dr. Hench and Dr. Kendall. Researchers knew about chemicals released by the adrenal cortex for years, but research in this area spiked with World War II on the horizon in 1941. To learn more about the development of "compound E" ― now called cortisone ― read Dr. Kendall's Nobel lecture from 1950.

Irina Bancos, M.D., a Mayo Clinic endocrinologist, is the senior author of the study. She has clinical and research expertise in adrenal tumors and was concerned about the lack of epidemiology studies in adrenal tumors. She believed there was a substantial gap in what the medical community knew about these tumors.

"The simple but important thing we discovered was a population-based proportion of malignant tumors, which is very helpful when discussing management with a patient newly diagnosed with an adrenal mass," she says.

The Numbers

Medical record review yielded 1,287 people diagnosed with adrenal tumors from 1995 to 2017. Due to increased use of medical imaging, the researchers found that diagnoses of any kind of adrenal tumor became 10 times more common by the end of the 23-year period.

The study examined medical records collected as part of the Rochester Epidemiology Project. Using information collected by the project, researchers can identify what causes diseases; how diseases may progress over time; and how patients with certain conditions respond to surgery, medication or other interventions. Drs. Bancos, Ebbehøj and team used this resource to look at the prevalence of adrenal tumors in one area (Olmsted County) from the beginning of 1995 through 2017.

'Incidentalomas'

Some patients were diagnosed with adrenal tumors as a primary diagnosis, but many, especially in the later years of the study period, had incidentalomas — a combination of the word “incidental,” meaning that the tumor was found while the patient was being examined for something else, and the suffix "-oma," which means tumor.

Of the incidentaloma group — which accounted for about 81.5% of the tumors found — some had malignant adrenal masses (3.3%) and a smaller group had obvious signs of elevated hormones (1.9%). Because the benign tumors without apparent signs of hormone excess vastly outnumbered the other more dangerous tumor types, "unfortunately our job of diagnosing the patients who might benefit from adrenal surgery just got a lot harder," says Dr. Ebbehøj.

"We also found that the clinical presentation and tumor characteristics tells us a lot about the tumor and whether it is likely to be malignant or not. For example, adrenal tumors in children, or any patients with another type of cancer, should be considered malignant until proven otherwise." Larger tumors were more likely to be malignant, as well.

These findings are why Dr. Bancos and the team wanted to conduct this research.

"I commonly see adrenal incidentalomas not considered important," says Dr. Bancos. "In this study, we show that any adrenal mass should be properly evaluated for both malignancy and hormonal excess before dismissing this problem."

Dr. Bancos is a Mayo Clinic endocrinologist with a deep research interest in adrenal tumors and finding the best treatments for her patients. You can read her response to the question of "What is adrenal insufficiency?" on the Mayo Clinic News Network.

Call to Action

In addition to the findings about the type and prevalence of different adrenal tumors, the researchers learned about what diagnostic tools and treatments are employed across the health care community.

"Most previous studies on adrenal tumors have been conducted at specialized endocrine centers by physicians who know the diagnostic guidelines by heart or even co-authored them," says Dr. Ebbehøj.

By using data from the Rochester Epidemiology Project, the team was able to include all patients from the community diagnosed with an adrenal tumor by all different types of health care providers.

"We were quite shocked when we learned that only 15.2% of patients had undergone the recommended biochemical testing for hormonal excess," say Dr. Ebbehøj.

A self-professed "adrenal nerd," Dr. Ebbehøj says he understands why this type of testing might be overlooked. After all, many of the tumors found are incidental to a work-up for cancer or other "acute unpleasantries." However, because many other chronic conditions, such as diabetes, osteoporosis and cardiovascular diseases, can be caused by excess hormones, he urges colleagues to send patients for an endocrine work-up. "An adrenal incidentaloma offers the physician a chance to prevent or even cure a patient from these diseases, but only if properly worked up. Otherwise, the discovery ends up being a wasted opportunity."

"In this particular case, the question of how common the dangerous adrenal subtypes are out of all the adrenal incidentalomas is key," says Dr. Ebbehøj, who is pursuing a doctoral degree at Aarhus University in Denmark. Photo Credit: Ida Marie Jensen, Aarhus University

"Our message is, again, to recognize the adrenal mass as a problem that needs full investigation at the time of discovery," reiterates Dr. Bancos.

The Value of Epidemiological Research

This study is an example of descriptive epidemiology, examining incidence, prevalence, morbidity and mortality. It describes the scope of adrenal tumors, which helps shared decision-making with patients. Prognosis, or the likely course and outcomes of a disease, are part of physician-patient conversations when deciding how to proceed.

"In this particular case, the question of how common the dangerous adrenal subtypes are out of all the adrenal incidentalomas is key," says Dr. Ebbehøj. "For example, you see a patient with an adrenal incidentaloma. It does not appear to produce hormones, and it does not seem to be malignant. But should you recommend a follow-up CT scan and repeated biochemical testing to be sure, when you know this means extra radiation, patient anxiety and costs? Or should you recommend surgery to be on the safe side? We need good epidemiological data to design rational guidelines that can balance between benefits and harms."

Dr. Bancos says she uses the results of this research daily when talking with her patients. "Clear understanding of the risk is very helpful in shared decision-making on the next steps in management."

"Outside the clinic, I agree with Andreas that epidemiology data is extremely important for development of guidelines and proposing intervention. Understanding what test needs to be done, and which time and in which sequence, is not only likely to achieve better health outcomes to our patients, and standardize and assure appropriate care, but will also save health care costs."

The researchers hope their study can be an example to other specialties and spur understanding of the broader presentation of particular conditions. Patients seen at an academic medical center such as Mayo Clinic or Aarhus University Hospital do not represent the overall patient group that is being managed by primary and secondary health care providers.

"Just like we need to include different sexes and races in our research, we should also consider whether our results are applicable outside our own specialized niches," says Dr. Ebbehøj.

"I completely agree," says Dr. Bancos. And now that she has evidence expanding the understanding of adrenal tumors, she hopes to see widespread practice change.

— Elizabeth Zimmermann, December 2020

*Dr. Young holds the Tyson Family Endocrinology Clinical Professorship, in Honor of Vahab Fatourechi, M.D.; Dr. Khosla is the Dr. Francis Chucker and Nathan Landow Research Professorship; and Dr. Rocca holds the Ralph S. and Beverley E. Caulkins Professorship in Neurodegenerative Diseases Research.

Authors who are currently affiliated with Mayo are Dr. Bancos, Dingfeng Li, M.D.; Ravinder Jeet Kaur, M.B.B.S.; Catherine Zhang, M.D.; Sumitabh Singh, M.B.B.S.; Elizabeth Atkinson; Sara Achenbach; Sundeep Khosla, M.D.*; William Young Jr., M.D.; and Walter Rocca, M.D. * Other authors are Dr. Ebbehøj of Aarhus University Hospital in Denmark, as well as Taoran Li, M.D., Mount Sinai Morningside, New York; and Wiebke Arlt, M.D., University of Birmingham and University Hospitals Birmingham NHS Foundation Trust in the United Kingdom. Assistance for this project was provided by Barbara Abbott and colleagues from the Rochester Epidemiology Project. Funding and other support were provided by the National Institutes of Health and the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The study was accompanied in The Lancet Diabetes & Endocrinology by an editorial, "Understanding the Epidemiology of Adrenal Tumours."