All About Adrenal: Analyzing Two Years of Research

ENDO_2022_4C

When the ENDO 2022 session “Clinical Year in Review: All Things Adrenal” gets underway, Gary Hammer, MD, PhD, will treat attendees to the series of advances that have been made in adrenal science and clinical practice over the last two years, from adrenal homeostasis, glucocorticoid biology, and adrenal insufficiency to Cushing’s, tumors, pheochromocytoma, and more.

The last time the annual meeting of the Endocrine Society was held in person was March 2019 in New Orleans, where the overall theme seemed to be collaboration — or more specifically, how big data sets could inform science and clinical care, and maybe, hopefully, one day go as far to cure all diseases.

It’s been more than three years since ENDO attendees gathered in the same convention center, and this meeting in Atlanta will feature a talk titled “Clinical Year in Review: All Things Adrenal” by Gary D. Hammer, MD, PhD, professor of Internal Medicine, Cell and Developmental Biology, and Molecular and Integrative Physiology at the University of Michigan in Ann Arbor, and past president of the Endocrine Society. (Hammer insists this isn’t his talk, but more on that later.)

The 45-minute session will cover some of the papers and studies on the adrenal gland that have come out in the past couple of years, covering pathophysiology, clinical questions, diagnosis, treatment, and more. Hammer says this talk is modeled on one Robert M. Carey, MD, gave at ENDO in 2011, when Carey was president of the Endocrine Society. Carey had asked 15 adrenal experts — including Hammer — to name their favorite papers from the past 18 months and then presented those. “I said, ‘We haven’t done this in 10 years. Let me go back at least five years and see what we’ve got,’” Hammer says.

There was plenty to choose from; in the past five years there have been more than 120,000 papers. And in the past two years especially, researchers and clinicians are discovering just how much big data is driving their work in the adrenal space. “This is an iterative process of discovery, and we’re learning more and more that big data and science is determining care,” Hammer says. “With that as a backdrop, I feel that as we move into the genomic era, I must talk about how science has impacted care and how care has impacted science.”

New Implications for Human Disease

Hammer tells Endocrine News that new and emerging technologies in single-cell biology have informed the medical community more and more about the growth and development of the adrenal gland. For instance, he says his lab has been focused on the interplay of the endocrine and paracrine systems. All organs have intrinsic paracrine systems embedded in them to regulate homeostatic control of stem cell renewal, while the endocrine system interfaces with the same organ, and scientists are finding that that intersection is where disease happens.

“We’re using big data sets now to be able to realize that disease is more prevalent and more nuanced than we thought, whether it’s adrenaline insufficiency, or hyperaldosteronism which is very complicated now. Big data has defined how we diagnose and treat disease, as we understand the genetics.”- Gary D. Hammer, MD, PhD, professor of Internal Medicine, Cell and Developmental Biology, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor; past president, Endocrine Society

And new technologies and research methods are starting to show it goes further than that. According to Hammer, biology studies using single-cell technologies have revealed the heterogeneity of even the fasciculata cortisol cells, where there’s at least 12 different populations of fasciculata cortisol cells that do different things, and that has implications for disease that show some polymorphisms in new mouse-determined unique clusters of the fasciculata. “That has implications for human disease,” Hammer says.

Hammer points to a paper published in the Journal of Clinical Investigation by Gerard Karsenty, MD, PhD, et al, showing that the bone hormone osteocalcin regulates the adrenal gland. Karsenty and his team used a mouse model to reveal that the bone-derived embryonic hormone influences lifelong adrenal functions and organismal homeostasis.

Then there’s the study led by Mitchell A. Lazar, MD, PhD, published in Cell Metabolism showing that glucocorticoid receptors vary by individual. Those variations are defined by polymorphisms, and those mutations affect how people respond to glucocorticoid therapy — using big data to again speak to the importance of personalized medicine. “Knowledge of the genetic variants that predispose individuals to metabolic side effects allows for a precision medicine approach to the use of clinically relevant [glucocorticoids],” Lazar and his team conclude.

“We’re using big data sets now to be able to realize that disease is more prevalent and more nuanced than we thought, whether it’s adrenaline insufficiency, or hyperaldosteronism which is very complicated now,” Hammer says. “Big data has defined how we diagnose and treat disease, as we understand the genetics.”

“I’m very excited about the possibility for all of us to gather and share advances across the scientific and clinical space live. What I hope to do in this review is to really show the advances of these last two or three years and really show how transformative the work has been despite the COVID epidemic.” – Gary D. Hammer, MD, PhD, professor of Internal Medicine, Cell and Developmental Biology, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor; past president, Endocrine Society

There can be a lot going on at these annual meetings, and attendees have to be judicious about what they sit down or tune in for. Clinicians might forego any basic science talk, and vice versa. But “Clinical Year in Review: All Things Adrenal” should have something for everyone. Hammer says he will cover adrenal homeostasis, glucocorticoid biology, adrenaline insufficiency, and then primary aldosteronism, Cushing’s, pheochromocytoma, and adrenal tumors, all from papers chosen by adrenal experts, which Hammer will then present. “I will be talking about basic science and how it impacts clinical care, and how the clinic has informed the scientific questions to ask over the last couple of years,” Hammer says.

Transformative Research

When Hammer took over as president of the Endocrine Society in 2020, the COVID-19 pandemic had just started to tighten its grip on the world, and he jokes that he was the “virtual president.” When ENDO 2020 had to pivot to an all-virtual platform, Hammer remained optimistic, saying at the time: “We envision that the meeting in 2021 will be a culmination of two years of outstanding endocrine science development, endocrine innovation, and clinical care. We will celebrate.”

And while it didn’t quite turn out that way, Hammer says he’s enthusiastic about this upcoming hybrid meeting and the things the endocrine community has continued to accomplish during such odd and difficult times. “I’m very excited about the possibility for all of us to gather and share advances across the scientific and clinical space live,” he says. “What I hope to do in this review is to really show the advances of these last two or three years and really show how transformative the work has been despite the COVID epidemic.”

Bagley is the senior editor of Endocrine News. In the April issue, he wrote about the possibility of how stem cell technology could potentially lead to a cure for diabetes.

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