MOLECU L AR TE STING AN D DIAG NOSING THYROID CANCE R

JANUARY 2024

THE LEADING MAGAZINE FOR

ENDOCRINOLOGISTSTHYROID CANCER
Diagnosis, Treatment,
Causes, and CareGETTING BACK TO NORMAL:
A look at a variety of newtreatment options forhypoparathyroidism
FOR YOUR INFORMATION:
Revealing new research highlights
thyroid cancer treatment
STANDARDIZED TESTING:
Why a universal risk stratification
system is needed for diagnosing
thyroid nodules

This image of a metastatic medullary thyroid carcinoma
to the liver was submitted by Anthony Y. Yin, MD,of the California Pacific Medical Center in San Francisco,as part of the Endocrine Society’s 2023 Endocrine
Images Art Competition, which celebrates the beauty of
endocrine science.

2024 ELECTION FOR

PRESIDENT-ELECT POSITION

Carol Lange, PhD
University of Minnesota
Minneapolis, MN

Jenny Visser, PhD
Erasmus University Medical Center
Rotterdam, The Netherlands

We encourage you to vote for our 2024 President-Elect.
Visit endocrine.org/election to learn more about thecandidates and cast your vote.
Questions? Contact election@endocrine.org or+1.202.971.3636 (or toll-free at +1.888.363.6274).
Ballots will be accepted throughThursday, February 29, 2024.

© 2024 ENDOCRINE SOCIETYIN THIS ISSUEJANUARY 2024

24 | Getting Back to Normal:

Options for Treating Hypoparathyroidism Endocrine News talks to
Aliya Khan, MD, about the debilitating effects of hypoparathyroidism, new treatment
guidelines she helped create, and exciting news from trials that showed promising
results that could allow these patients to have a much-improved quality of life, both
physically and psychologically.
BY DEREK BAGLEY

30 | Standardized Testing: Universal RiskStratification System Needed for Thyroid Nodules

18 | For Your Information
Recent Revelations on Thyroid Cancer
Treatment Thyroid cancer is the most common

endocrine cancer in the world with more than 62,000
newly diagnosed cases each year in the U.S. alone. Here,
we look at some of the latest research that includes a
study from Endocrine Reviews on radiation-induced thyroid
cancer; a JCEM Case Reports paper on false-positive
results in metastatic thyroid cancer; and a presentationfrom ENDO 2023 that looks at thyroid cancer survival.
BY KELLY HORVATH

2 | PRESIDENT’S VIEWPOINT
Harnessing the Power ofProfessional Development

4 | FROM THE EDITOR
Focusing on Thyroid Cancer

6 | TRENDS & INSIGHTS
Teprotumumab improves
proptosis in TED; Testosterone
therapy for transmasculine
individuals may be safer
than previously thought; andInvestigational drug restoresparathyroid function in raredisease.
BY DEREK BAGLEYEARLY-CAREER CORNER
With thyroid cancer patients often getting different — and sometimes conflicting— treatment recommendations from a variety of diagnostic tools, Priyanka Majety,
MD, talks to Endocrine News about why it’s time for clinicians to coalesce arounda single set of standards for these cases, which could potentially eliminate
unnecessary procedures.
BY DEREK BAGLEY

34 | Molecular Testing and the

Future of Diagnosing Thyroid Cancer
PRACTICE RESOURCES
Endocrine Society member and medical director for Endocrinology for Veracyte,
Joshua Klopper, MD, talks to Endocrine News about a new tool that may havethe potential to guide thyroid cancer management decisions by predicting tumor
behavior via molecular signatures.
BY KELLY HORVATH

11 | INTOUCH

38 | ADVOCACYJameson named interim
president at Penn; Remembering
John Nilson, PhD; andEndocrine Society weighs in on
Senate HELP hearing.

2023: A Year in Advocacy
Accomplishments

16 | ENDOCRINE ITINERARY
Scientific meetings of interest
to endocrinologists from aroundthe world

www.endocrine.org
ABOUT THE COVER: Metastatic medullary thyroid carcinoma to the liver: The original image was a 400x hematoxylin and eosinstained slide for conventional light microscopy documenting pathology confirmation of metastatic medullary thyroid carcinoma
to the liver. The image was subsequently modified with solarizing effect and central ballooning expansion of the neoplastic
deposit. Peritumoral endothelialized capillaries are enhanced by aqua staining; and erythrocytes are further delineatedby magenta staining, capturing the inherent capacity for these rare malignancies to characteristically disseminate via theperipheral vascular system. Originally submitted by Anthony Yin, MD, Drayson Jaffee; Anthony Yin, MD; and Ian Jaffee, MD.

Follow us on Twitter:@Endocrine_News

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |1PRESIDENT’S VIEWPOINT

Harnessing the Power of Professional Development“ T

Throughout the year, we
provide opportunities to expand
your horizons and meet individuals
who share your interests.
We are making the most of digitalplatforms to allow you to accessthe resources you need atyour convenience.

”

he start of a new year offers an ideal time to reflect on our careergoals and what we need to do to achieve them. As your professional
home, the Endocrine Society offers a myriad of opportunities tohelp build your CV and advance your career.
This is an ideal time to register for our annual meeting, ENDO 2024, andstart thinking about ways you can make the most of your time in Boston,
Mass. The meeting will take place from June 1 to 4. Applications for manyof our ENDO travel grants and the Early Investigator Awards are due thismonth. These programs help ensure early-career researchers who havesubmitted abstracts can take advantage of ENDO’s amazing networking
opportunities and be exposed to emerging science.
Another way to meet your peers and build new professional relationships is
to attend our Type 1 Diabetes Fellows Series event, which precedes ENDO
2024. This program, which will be held May 30-31, provides comprehensive
education on type 1 diabetes care and gives fellows extensive opportunities
to connect with leading experts in the field. Applications are due this month,and fellows who are invited to attend will receive complimentary ENDO
2024 registration as well as a travel stipend. This is an excellent opportunity
to form new connections in an intimate setting.
ENDO 2024 also will feature a career fair, a full slate of Career Development
Workshops, and other opportunities for professional development. These
include the popular Early Career Forum, held the day before the meeting.
The Early Career Forum offers graduate and medical students, postdoctoraland clinical fellows, and internal medicine residents a unique opportunity toconnect with today’s leading endocrine professionals. The deadline to apply
is Jan. 20. We also will be hosting our second Endocrinology Mentor Day,
which is designed to educate medical students and residents from the Boston
area about the endocrinology field. We are proud to offer these opportunities
to position the next generation of endocrinologists for success.
There is still time to submit a late-breaking abstract for presentation at
ENDO 2024. Watch your inbox for announcements about the submission
process, which is scheduled to take place from March 19 to April 10.

2 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

In addition to ENDO, we offer numerous opportunities
for learning and career development throughout the year.
This spring, we’ll be holding our Future Leaders Advancing
Research in Endocrinology (FLARE) and Excellence in Clinical
Endocrinology Leadership (ExCEL) workshops. These inperson sessions allow early-career clinicians and researchers
from underrecognized groups to receive comprehensive
leadership training and mentorship. We inspire the next
generation of leaders with a space and caring network that
includes tools and contacts they need to set up and operate
successful labs and/or practices.
Throughout the year, we provide opportunities to expand yourhorizons and meet individuals who share your interests. We aremaking the most of digital platforms to allow you to access theresources you need at your convenience. Our DocMatter online
community gives you a venue to ask questions and collaborate
with fellow Society members in real time. Through our Special
Interest Groups, you can connect with peers who share yourpassion for specific endocrine topics and attend educational
webinars. Our Center for Learning makes it easy for you toaccess educational materials about a variety of topics and toearn the continuing education credits you need. And, you cansearch for new career opportunities on your schedule using our
EndoCareers site. These and a host of other tools are at yourdisposal as you look for ways to advance your career this year
and beyond.
You also have an important opportunity to influence thedirection of the Society. Voting is now open for our nextpresident-elect, whose term will begin in June 2024. This is yourchance to shape the future of the Society and our field, so please
make sure to cast your ballot!

ENDO 2023
SESSION
RECORDINGSVIEW MORE THAN
150 SESSIONS AND
EARN UP TO 110 CME
CREDITSP U R C H A S E T O D AY

Stephen R. Hammes, MD, PhD
President, Endocrine Society© 2023 ENDOCRINE SOCIETY

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |3FROM THE EDITORJANUARY 2024

THE LEADING MAGAZINE FOR ENDOCRINOLOGISTS

Executive Editor: Mark A. Newman
mnewman@endocrine.org
Senior Editor: Derek Bagleydbagley@endocrine.org
Art Director/Production: Anthony S. Picco
aspicco.wixsite.com/graphicdesigner

Focusing on Thyroid CancerAs we start the year, we are devoting the lion’s share of the editorial
pages this month to thyroid cancer. From its diagnosis andtreatment to detailed studies about hypoparathyroidism, risk
stratification for thyroid nodules, and more. With thyroid cancer being
the most common endocrine cancer in the world, we thought it would beappropriate to devote this issue to its treatment and research.
New research from the world of thyroid cancer is featured in “For Your
Information: Recent Revelations on Thyroid Cancer Treatment,” by
Kelly Horvath on page 18. And, as is often the case, we are highlighting
research from two Endocrine Society journals as well as a presentationfrom ENDO 2023 in Chicago! Kelly has included a mesmerizing study
from Endocrine Reviews on radiation-induced thyroid cancer, a JCEM
Case Reports paper on false-positive results in metastatic thyroid cancer,
and a presentation from ENDO 2023 that looks at thyroid cancer
survival. According to Megan Haymart, MD, the Nancy Wigginton
Endocrinology Research Professor in Thyroid Cancer and a professorof medicine at the University of Michigan in Ann Arbor, we are now inan era of more personalized and tailored management of thyroid cancer.
“However, there are both advantages and disadvantages to less-intensive
treatment,” she says. “For example, although surgical risks are greaterwith more intensive treatment, the long-term follow-up is more difficultin patients who received less-intensive surgical or medical management(e.g., less use of radioactive iodine).”In “Getting Back to Normal: Options for Treating
Hypoparathyroidism” on page 24, senior editor Derek Bagley talks to
Aliya Khan, MD, about the debilitating effects of hypoparathyroidism,
as well as some new treatment guidelines she helped create. She also
discusses exciting news from trials that showed promising results that
could actually lead to a much-improved quality of life for these patients,
both physically and psychologically. Khan details one patient in particular
who found relief from his hypoparathyroidism after participating ina clinical trial of a prodrug that replaced parathyroid hormone. Thispatient’s symptoms were so severe that not only did he have recurrent

4 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

Art Director/Design: Catherine C. Neill,
CNJ Creative, saLLC
www.cnjcreative.com
Prepress & Printing: The Sheridan Groupwww.sheridan.com
Endocrine News is a registered trademark owned by the
Endocrine Society.
Endocrine News informs and engages the global endocrine
community by delivering timely, accurate, and trusted
content covering the practice, research, and profession of
endocrinology.

President: Stephen Hammes, MD, PhD
president@endocrine.org
President-Elect: John Newell-Price, MD, PhD, FRCP
j.newellprice@sheffield.ac.uk
Past-President: Ursula B. Kaiser, MDukaiser@bwh.harvard.edu
Secretary-Treasurer: Jeffrey Boord, MD
jeffrey.boord@parkview.com
Chief Communications Officer: Aaron Lohralohr@endocrine.org
The mission of the Endocrine Society is to advance excellencein endocrinology and promote its essential and integrative rolein scientific discovery, medical practice, and human health.

Endocrine News® is published 12 times a yearby the Endocrine Society, 2055 L Street, NW,
Suite 600, Washington, DC 20036
Phone 202-971-3636 • Fax 202-736-9708
www.endocrine.org.
Print ISSN 2157-2089 Online ISSN 2157-2097
Copyright © 2024 by the Endocrine Society.
All rights reserved.
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kidney stones throughout his life, but he also experienced
seizures that limited his activities. “If you’re having seizures
and you don’t know when you could have a seizure, that
affects your ability to swim or do sports activities that otherpeople take for granted because they know they’re not goingto have a seizure,” she says, adding that he could have a
seizure while he was swimming and potentially drown.
Originally, when we envisioned the Early-Career Corner
department that launched last year, we thought it would
be quarterly, if that often. Turns out, it has been monthly
because the Endocrine Society’s early-career members arebusy! On page 30, Derek speaks with Priyanka Majety, MD,
in “Standardized Testing: Universal Risk Stratification
System Needed for Thyroid Nodules,” who discusses
why clinicians — not just endocrinologists, but generalpractitioners and other specialties as well — need tocoalesce around a single set of standards for evaluating
thyroid nodules. She says that in many cases, thyroid cancer
patients often get different, and even conflicting, treatment
recommendations from various diagnostic tools. One set ofstandards could bring that to an end.
The unpredictable nature of tumor behavior is the subjectof this month’s Practice Resources column by Kelly Horvathon page 24. In “Molecular Testing and the Future of
Diagnosing Thyroid Cancer,” Joshua Klopper, MD, themedical director for Endocrinology at diagnostics company
Veracyte, discusses a new tool that could help physicians maketreatment decisions by using molecular signatures to home inon how the tumor could react. Klopper refers to three separate
posters on the new tool that were presented in September at
the annual American Thyroid Association Annual Meeting inWashington, D.C.
Feel free to let us know what you think of this thyroid
cancer issue. This theme essentially evolved from the topic
being both timely as well as yielding various stories all
interconnected one way or the other. As usual, if you haveany other questions, comments, or ideas, let me know at:
mnewman@endocrine.org.

EVALUATE YOURK NOWLEDGE
WITH THE LEADING SELF-ASSESSMENT
PROGRAM IN PEDIATRIC ENDOCRINOLOGY• 100 brand-new case questions• A hard copy of the book to
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O RDER O N LIN E AT
EN DO C RIN E.O RG/S TO RE/P ES A P 2023- 20 24— Mark A. Newman, Executive Editor, Endocrine News© 2023 ENDOCRINE SOCIETYTRENDS & INSIGHTSBY DEREK BAGLEY
Senior Editor

Teprotumumab Improves
Proptosis in Thyroid Eye Disease

T“

These data
demonstrate that
teprotumumab
significantly
reduced proptosis
from baseline
with a higher rateof proptosis
response comparedwith placebo inpatients withlongstanding
TED and low
clinical diseaseactivity.

”

eprotumumab significantly improved
proptosis versus placebo in longstanding/
low-inflammation thyroid eye disease(TED) according to data from the first placebocontrolled trial of the drug that was recently
published in The Journal of Clinical Endocrinology& Metabolism. (Horizon Therapeutics funded thetrial and is marketing the drug as TEPEZZA.)
Researchers led by Raymond S. Douglas, MD, PhD,of the Department of Ophthalmology at Cedars
Sinai Medical Center in Los Angeles, point out
that early TED can lead to symptomatic chronic
disease, including proptosis, which canbe debilitating. In 2020, teprotumumab,
an insulin-like growth factor-1 receptor(IGF-1R) inhibitor, was the first drug
approved for TED treatment in the
U.S. and has been recommended as thefirst-line treatment for a wide group ofpatients with moderate to severe TED
presenting with active inflammationand significant proptosis and/or
diplopia.
“Althoughseveralobservational
reports have been published indicating
favorable effects of teprotumumab in awide group of patients with chronic TED, there are
no well-controlled study data with teprotumumabin patients with longer duration of TED without
active inflammation,” the authors write. “Wereport results of the first randomized, doublemasked, placebo-controlled trial in patients with
TED with low clinical activity. The objective of
this study was to investigate the efficacy, safety,
and tolerability of teprotumumab in patients withlong-duration TED and low disease activity asassessed by the [Clinical Activity Score (CAS)].”For this study, the researchers randomized 62

6 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

adult participants who have had TED for two to
10 years. Forty-two patients received intravenous
teprotumumab once every three weeks for a totalof eight infusions, while 20 received placebo. At
week 24, proptosis improvement was greater withteprotumumab than with placebo. “Patients inthis trial had a statistically significant decrease, asassessed by [least squares] mean changes in mmof proptosis and a higher percentage of patientswith a 2-mm reduction from baseline (62%)
as compared with placebo,” the authors write.
(Adverse effects like hyperglycemia and hearing
impairment were also noted, as in previous

teprotumumab trials.)“The results from this randomized controlled
study add to the increasing body of literature fromreal-world clinical practice on teprotumumab's
efficacy in treating TED,” the authors conclude.
“These data demonstrate that teprotumumab
significantly reduced proptosis from baseline
with a higher rate of proptosis response comparedwith placebo in patients with longstanding TED
and low clinical disease activity.”Testosterone Therapy forTransmasculine Individuals May Be
Safer Than Previously ThoughtAcommon concern about gender-affirming
hormone therapy for transmasculine
people is the risk of red blood cell volume
changes and erythrocytosis, a high concentrationof red blood cells, with the use of prescribedtestosterone. However, Mount Sinai researchers
have found that testosterone treatment may
be safer than previously reported, with results
published recently in The Journal of Clinical
Endocrinology & Metabolism.
Mount Sinai researchers from the Division of
Endocrinology and Center for Transgender
Medicine and Surgery examined the relationshipbetween the use of testosterone as part ofgender-affirming hormone therapy (GAHT)
for transmasculine individuals and changes inhematocrit. The study of a large North Americancohort is the largest on this subject to date.
“A major concern of patients, providers, andparents is the safety of hormone therapy fortransgender and gender-diverse people. The
findings from this study represent very importantreassurance regarding the safety of testosterone
as masculinizing treatment,” says senior author
Joshua Safer, MD, FACP, executive director of theMount Sinai Center for Transgender Medicine
and Surgery, professor of Medicine at the Icahn
School of Medicine at Mount Sinai, New York,
N.Y. “Providers should feel more comfortableprescribing testosterone when it is indicated.
Patients and the families of patients should feelreassured regarding at least this one source ofanxiety about treatment.”
The researchers conducted a cross-sectional
analysis of serum-based testosterone andhematocrit levels in 6,670 transmasculine
patients who were prescribed testosterone for
GAHT through Plume, a virtual provider ofgender-affirming care across 45 states. Patientswere included if they had an active prescription

from Plume for a testosterone product as partof their GAHT regimen, and recent hematocrit
and testosterone laboratory values available foranalysis. The total testosterone was measured
using liquid chromatography-mass spectrometry,and hematocrit was calculated as part of acomplete blood count. The hematocrit andtestosterone laboratory values were collected aspart of the same blood sample, typically midweek after a weekly injection, for all patients using
injectable forms of testosterone.
Researchers found that higher testosterone levels
were associated with higher hematocrit levels;
however, the magnitude of change in hematocrit
was small and unlikely to be clinically meaningful.
Only 8.4% of transmasculine individuals in the
study had a hematocrit greater than 50%, andless than 1% had a hematocrit greater than 54%,
the level at which treatment for erythrocytosis is
recommended, often using phlebotomy. These
numbers are lower than those previously reported
in smaller studies, and the finding of such a small
degree of change in hematocrit and a lower risk oferythrocytosis should provide more assurance tothose prescribing and using testosterone as GAHT.
“Our study found that the numbers of patients on
testosterone therapy with abnormal red blood cell
elevations were lower than previously reported insmaller studies. It’s noteworthy that in the largest
North American cohort reported to date, less than
1% of transmasculine individuals had a hematocrit
level where medical interventions might berequired. These results should help providers feel
more comfortable prescribing testosterone as partof GAHT,” says the first and corresponding author,
Nithya Krishnamurthy, a second-year medical
student at Icahn Mount Sinai. “This work suggests
a need to assess the influence of other factors thatcan lead to secondary erythrocytosis, such as being
overweight, smoking tobacco, or using alcohol.”“

A major concernof patients,
providers, andparents is the safetyof hormone therapy
for transgenderand gender-diverse
people. The
findings fromthis study representvery importantreassurance
regarding thesafety of
testosterone as
masculinizing
treatment.

”

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |7Investigational Drug Restores
Parathyroid Function in Rare Disease“

It wasamazing to seethat every
participant
responded to thetreatment.
In literally
minutes after
taking the
medication
orally, the levelsof parathyroid
hormone increased
dramatically.

An investigational drug, encaleret, restoredcalcium levels in people with autosomal
dominant hypocalcemia type 1 (ADH1).
Results from the clinical trial, which was led byclinician-scientists from the National Institute of
Dental and Craniofacial Research (NIDCR) at the
National Institutes of Health’s Clinical Center, arepublished in the New England Journal of Medicine.
In the mid-phase clinical trial, 13 participants with
ADH1 received oral doses of the investigational
drug for about 24 weeks. By the end of the trial,”

the treatment restored every participant’s blood
calcium level to normal, and urine calcium
approached normal levels. Levels of parathyroid
hormone also normalized.
“It was amazing to see that every participant
responded to the treatment. In literally minutes
after taking the medication orally, the levels ofparathyroid hormone increased dramatically,”
says senior author and NIDCR endocrinologist
Michael Collins, MD.
“Conventional therapy is to raise the blood
calcium level with calcium supplements andactivated vitamin D,” says principal investigatorand NIDCR pediatric endocrinologist Rachel
Gafni, MD. “However, too much of an increase

8 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

could cause kidney stones or damage kidney
tissues, leading to kidney failure in worst-casescenarios. The patients need better treatments, so
we’re not constantly walking on a tightrope.”
Encaleret is thought to exert its effects by acting on
faulty calcium-sensing receptors that are peppered
throughout the kidneys and the parathyroid
glands. In healthy people, these receptors act likethermostats to monitor and control calcium levels.
However, in patients with ADH1, the receptors are
too sensitive and falsely interpret normal blood
calcium levels as high. As a result,the parathyroid glands do not makeenough parathyroid hormone, andthe kidneys flush too much calcium
out of the body. This leads to low
calcium levels in the blood and highlevels in the urine.
Encaleret appeared to be safe andcaused no serious side effects.
However, because parathyroid
hormone raises blood calcium levels
in part by drawing calcium fromthe bones, the researchers noted aneed to assess the treatment’s long-term effects
on the skeleton. The researchers also speculate
encaleret may have broader implications. An
ongoing clinical trial led by Collins and NIDCR
staff clinician Iris Hartley, MD, is testing whether
the treatment can help correct calcium levels
in people whose parathyroid glands have beendamaged by surgery.
“Because ADH1 can be passed on to offspring, theparticipants are not just doing this for themselves;it’s for their children, grandchildren, and greatgrandchildren,” Gafni says. “One day, hopefully,
we’ll be writing prescriptions for an effective
treatment thanks to them.”

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ENDOCRINE SOCIETY PRESENTSENDOCRINE DISCOVERC O M I N GS O O NT O

AD E V I C E

N E A RY O UThe Endocrine Society is excited to introduce Endocrine Discover, a powerful online search and discovery
tool developed with our technology partners. Soon, users will have access to a powerful platform thatenables real-time searches and curated collections across all Endocrine Society content, including:

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This innovative tool will enable users, from a single interface, to search for and discover key words and other meta-datain the wealth of information produced through the Endocrine Society’s multiple channels, then either proceed to view thefree-to-view content, use their member ID to view content that is access-controlled, or contact the Society.

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For content licensing inquiries, contact licensing@endocrine.org.

© 2024 ENDOCRINE SOCIETYBERS
MEM thein

INTOUCHS

NEWJameson Named Interim President at Penn

J

. Larry Jameson, MD, PhD, was named interim president of the
University of Pennsylvania in a unanimous motion by the school’sboard of trustees last month. Jameson had previously served as deanof Penn’s Perelman School of Medicine.
“Penn is a remarkable institution that I am honored and humbled to leadand serve,” Jameson says. “Penn, like so many of your institutions, ispoised to make breakthroughs – like the mRNA platform for vaccinesand gene therapy that was recently recognized with the Nobel Prize.”
The news comes after the university’s former president, Liz Magill,
stepped down amid criticism stemming from Magill’s controversial
remarks at a Congressional hearing.
A past-president of the Endocrine Society and former editor-in-chiefof the Journal of the Endocrine Society — among many other leadershiproles, both in academia and within the Society — Jameson has been at
the helm of the medical community in one form or another since hejoined Northwestern University Medical School as chief of the Division
of Endocrinology, Metabolism, and Molecular Medicine in 1993.
One example of Jameson’s leadership in a difficult time came in a March
2020 opinion piece he wrote for The New York Times on behalf of himself
and six other medical experts, urging national leadership to continuesocial-distancing policies. “It will be important for us to continue toemphasize a social contract in which we support one another to getthrough this as effectively as possible,” he told Endocrine News at the time.

Now, Jameson says he hopes that stewardship will help inform his new role.
“I served as president of the Endocrine Society in 2000, and that leadershipexperience was transformative for me given the breadth of the endocrine
community, the rapid changes in the field, and access to the extraordinary
mentors in our Society,” he says. “The field of endocrinology, founded on
concepts of systems thinking, feedback loops, and homeostasis, is a natural
one for today’s leaders. I hope those with similar endocrine backgrounds
will also contribute as academic leaders.”— Derek Bagley

J. Larry Jameson, MD, PhD“

The field of endocrinology,
founded on concepts of systems
thinking, feedback loops, andhomeostasis, is a natural one
for today’s leaders.
I hope those with similar
endocrine backgrounds
will also contributeas academic leaders.

”

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |11INTOUCH

Remembering John H. Nilson, PhD(1950 – 2023)
John H. Nilson, PhD

By Ruth A. Keri, Joan S. Jorgensen, Helai P. Mohammad, and Mary Hunzicker-DunnT

he research world has lost an innovator, mentor,
advocate, and friend. It is with great sadness that the
Endocrine Society reports that John Helmer Nilson,
former editor-in-chief of Molecular Endocrinology, vicepresident for basic science, and recipient of the 2011 Sidney
H. Ingbar Award for Distinguished Service, passed away in
September while on holiday in Sardinia, Italy.
Born on July 12, 1950, in Mankato, Minnesota, John spent his
formative years with his family in Albuquerque, N.M. Afterconsidering a major in religion and being told that the “church
wasn’t ready for him yet,” he ultimately earned a Bachelor of
Science degree in zoology from the University of Tulsa. He
then completed his doctorate in biology at the University of
New Mexico, working with Robert O. Kelley on the regulationof adenylate cyclase by glycosaminoglycans. During this time,
John became very interested in RNA and the developing fieldof molecular biology. Thus, he joined the laboratory of Fritz
Rottman who was at the forefront of discerning mechanisms
controlling RNA processing at Michigan State University. It
was here that John began his long journey of innovation in
the field of molecular endocrinology and the transcriptional
regulation of reproduction, by first cloning the bovine
prolactin gene. He also characterized the developmental
patterns of prolactin and growth hormone gene expression inbovine pituitaries.
In 1980, John started his independent academic career as

12 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

an assistant professor of pharmacology at the Case Western
Reserve University School of Medicine. He rapidly became“

While he made tremendous
contributions to science inmany ways, John will be mostremembered for his exceptional
mentorship and sponsorship of his
own trainees and others who he met
along the way. He had an uncanny
knack for identifying people who'just needed a chance to prove
themselves' and he gave them theplatform to accomplish allthat they could achieve.

”a leader in his field by using state-of-the-art techniques tofirst clone, and then probe the transcriptional control of the
gonadotropin genes. John was fearless in his approach andINTOUCH

used all methods available to him. This included being at theforefront of using transgenic technology to interrogate gene
regulation when no cell lines were available to accomplish
such a task. John rapidly moved through the ranks ofacademia to become the John H. Hord Professor and chair ofpharmacology at CWRU from 1997 to 2003 and then moved
to Washington State University to become the Edward R.
Meyer Distinguished Professor and director of the School ofMolecular Biosciences at Washington State University.
During his research career, he remained highly productive andwas sought after by many peer review panels for his insights
into molecular biology and physiology and his “tough, butfair” approach. In 1998, he assumed the role of editor-in-chief(EIC) of the Endocrine Society’s Molecular Endocrinology,
where he transformed the journal into a working partnership
between editors, reviewers, and readers that published thehighest quality of science discovering the molecular basisof endocrine systems. He and his team evolved the journal
by shepherding it into the digital age, designing and testing
an approach that was then adopted by the companion
Endocrine Society journals. In his editorial on the merging
of the journal with Endocrinology, John stated that Molecular
Endocrinology was “dedicated to maintaining the highest
standards of scholarly science” and that he was thankful forthe “opportunity and for the trust it entailed.”
Immediately after completing his term as EIC, John took on
a greater role in the Society by being elected vice president
for basic science in 2003 for a two-year term. Here, he wasan ardent advocate for ensuring basic science inclusion in all
aspects of the Endocrine Society. For his many contributions to
the Society, John received the Sidney H. Ingbar DistinguishedService Award in 2011. His interests in the molecular basisof endocrinology also fostered his service to the Society for
the Study of Reproduction, where he provided keen insights

into its publications committee; was a member of its board of
directors; and ultimately, served as its president during the
2009-2010 term.
In addition to his innovation in these realms, John was aheadof his time in other arenas. As chair of his department at
CWRU, he was one of the first at his school to recognize thatbusiness principles were relevant and useful in the academic
setting. He worked with an organizational coach to use various
established instruments in business to build integrated
collaborative teams among the faculty, trainees, and staff.

Announcing the Nilson Award
In recognition of Dr. Nilson’s distinguished career
as a basic scientist and his commitment to mentorshipand career development, the Endocrine Society has
created the John H. Nilson Travel Award for Exceptional
Basic Science Research. This annual award will recognize
innovative research in molecular endocrinology by adoctoral graduate student or postdoctoral fellow.
The Society invites the endocrine community to honor
Dr. Nilson’s legacy with a donation in support of thisaward. Advances in basic science research are at thecenter of improving our understanding of endocrinology
and the development of new treatments for patientswith endocrine disorders. We hope you will join us
in supporting young endocrine basic scientists andrecognizing Dr. Nilson’s contributions to our field.
You can contribute to the Nilson Award here: https://www.endocrine.org/membership/make-a-donation.
On behalf of Dr. Nilson’s friends and colleagues,
thank you for your support.

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |13

INTOUCH

In the classroom, he strove to diminish the complexity of
feedback loops in endocrinology by relating to the everyday
experiences of students, including the use of a golf club to
explain the hypophyseal portal system. As the leader of theMedical Scientist Training Program at CWRU, he routinely
developed extracurricular activities to break down barriers
between students and faculty.
While he made tremendous contributions to science in many
ways, John will be most remembered for his exceptional
mentorship and sponsorship of his own trainees and others
who he met along the way. He had an uncanny knack for
identifying people who “just needed a chance to prove
themselves” and he gave them the platform to accomplish allthat they could achieve. A look at the numbers from his own“

As a result of his unwavering
dedication to fostering the growthand innovative thinking of his mentees,
John will always be remembered
as a person, who, above all, cared.
He was a champion of the underdog,
wordsmith, innovator, confidant,
master of puns, lover of life, and,most importantly, generous and kind.

”laboratory tells just part of the story: More than 30 graduate
students, postdoctoral fellows, and physician-scientists
completed their training with him and were highly successful.
This includes 19 professors, chairs, and vice presidents ofuniversities; four founders, vice presidents, and directors of
biotechnology/pharmaceutical companies; and two program

14 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

leaders in government agencies. More than 50% of his trainees
were women or from underrepresented groups. His reach also
extended beyond his own laboratory to include many mentees
from other departments and universities. He was always readyto listen and provide advice. He often said that “their success
was his success” and he was fully committed to them.
As a result of his unwavering dedication to fostering the growthand innovative thinking of his mentees, John will always
be remembered as a person, who above all, cared. He was achampion of the underdog, wordsmith, innovator, confidant,
master of puns, lover of life, and, most importantly, generous
and kind. One of his former trainees stated a common refrain:“I know that I would not be where I am today without John
giving me the opportunity to work in his lab and his going togreat lengths to make sure I had every opportunity to succeed.”
John, being ever cognizant of his role in developing scientists,then chose to retire at age 65 to ensure room for new ideas andapproaches by the next generation. He moved with his wife,
Mary Hunzicker-Dunn, herself a leader in the field of ovarian
biology, to Taos, N.M., to begin a new adventure, continuing
to learn about life, fishing, golfing, and how to navigate an
Airstream across the United States. While John Nilson will begreatly missed, his trainees have learned to “pay it forward”
and will continue his legacy of leadership, joy at discovering
the unknown, and support of those in need.
– Ruth A. Keri, PhD, staff, Cancer Biology, Lerner ResearchInstitute, Cleveland Clinic; professor, Molecular Medicine,
Cleveland Clinic Learner College of Medicine; associate
director for Basic Research, Case Comprehensive Cancer
Center; Case Western Reserve University School of Medicine,
Cleveland, Ohio; Joan S. Jorgensen, DVM, PhD, professor,
Department of Comparative Biosciences; director, UWMadison PREP; School of Veterinary Medicine, University of
Wisconsin, Madison; Helai Mohammad, PhD, vice president;
head of Biology, SK Life Science Labs; King of Prussia, Pa.;
and Mary Hunzicker-Dunn, PhD, professor emeritus, Schoolof Molecular Biosciences, Washington State University,
Pullman, Wash.

INTOUCH

Endocrine Society Recommends Bipartisan Solutions to
Senate HELP Hearing on Diabetes, Obesity

T

he Endocrine Society commends the Senate Health,
Education, Labor, and Pensions (HELP) Committee
for calling attention to the issues that are fuelingthe diabetes epidemic in its December 14 hearing and urges
the Committee to support bipartisan legislation to begin toaddress the crisis in our country.
More than 38 million Americans have diabetes, and, while
we have the medications and technologies to treat people

research on diabetes. People with diabetes and obesity
deserve access to affordable healthcare that will improve their
quality of life.”
The Endocrine Society urges Congress to support thefollowing bipartisan legislation to address the diabetes crisis
in our country:uReauthorize the Special Diabetes Program (SDP)
before January 19 — SDP is a bipartisan program createdin 1997 that funds critical research being done on type1 diabetes and type 2 diabetes education and treatment
programs for American Indians and Alaska Natives. The
Endocrine Society urges Congress to reauthorize SDP
through the end of 2025 at $170 million per program, peryear, which is a 13% increase in current funding.

uliving with the disease, access and affordability remain anissue. Obesity, which is a major risk factor for diabetes, affects
more than 40% of Americans. Several promising anti-obesity
medications are available, but supply and cost are major
roadblocks, and congressional action is needed to allow
Medicare to cover these medications.
“It’s time for Congress to take action and pass legislation
to help the millions of people with chronic conditions,
including diabetes and obesity, by making their healthcare
more affordable and accessible, and by supporting thediabetes research and prevention programs that have been
crucial in our fight against this disease,” says the chair of theSociety’s Clinical Affairs Core Committee Joshua Joseph,
MD, MPH, of The Ohio State University Wexner Medical
Center in Columbus, Ohio. “The Endocrine Society has longadvocated to remediate the access and affordability issues thatare contributing to the diabetes and obesity epidemics whilestrengthening the programs that deliver groundbreaking

Pass the bipartisan INSULIN Act of 2023 — Thislegislation, introduced by the co-chairs of the Senate
Diabetes Caucus, Sens. Jeanne Shaheen (D-NH) and Susan
Collins (R-ME), includes several policies to make insulin
more affordable. It would expand the $35 insulin co-pay
cap, which is currently available for people on Medicare,to the private insurance market. The legislation would
also ensure that people who rely on insulin are able toshare in insulin rebates and discounts, which often go topharmacy benefit managers and private insurers. Finally,
the legislation would promote competition by encouraging
the approval of additional generic and biosimilar insulins.

uPass the Treat and Reduce Obesity Act (TROA) —There are groundbreaking Food and Drug Administrationapproved medications on the market to treat obesity,and scientific studies have shown these medications are
effective. Currently, however, Medicare is prohibited bystatute from covering these anti-obesity medications,and congressional action is needed. TROA would allow
Medicare to cover anti-obesity medications. We urge the
Senate to pass this bipartisan legislation.

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |15

ENDOCRINE ITINERARY

June 1 – 4, 2024 • Boston, Mass.

We hope to see you at ENDO 2024, taking
place June 1 – 4, 2024, in Boston, Mass. With
over 7,000 attendees, nearly 2,000 abstracts,
and over 200 other sessions, ENDO is the top
global meeting on endocrinology research andclinical care. ENDO provides the opportunity
to collaborate with an unparalleled list of
endocrinologists, healthcare practitioners, andleading scientists from around the world. Throughsharing our experience, advice on patient care,and new advances in research, we move theneedle forward in hormone health and science.
Our outstanding slate of world-renowned speakers
will showcase the most cutting-edge advancesin research and medicine, with presentations
spanning the spectrum of science, clinical care,and social implications. https://www.endocrine.
org/meetings-and-events/endo-2024

2024 CDEI

can look forward to dynamic speakers,
presentations of innovative research,
opportunities to connect with colleagues,
and informative panel discussions. This
year’s pre-meeting Advanced Course in
Endocrine Surgery will include outstanding
faculty and a wide range of topics. In
addition, sponsors will be on site toshowcase cutting-edge technologicaladvancements pertinent to the practiceSnowmass, Colorado
January 20 – 23, 2024
The 59th Annual Clinical Diabetes andEndocrinology Institute CME Conference willaddress updates in hormonal contraception,transgender health guidelines, thyroid
nodules, lipids, management of thyroid
cancer, obesity, Cushing syndrome, type2 diabetes, and much more. The faculty,
composed of known experts, will offer
insights, latest research, case presentations,and clinical guidelines.

https://www.eventsquid.com/event.
cfm?id=20903

BPS 2024

Philadelphia, Pennsylvania
February 10 – 14, 2024
At the Biophysical Society’s BPS 2024, thesymposia and workshops are as exciting as
ever, with a slate of invited speakers that
represent breakthrough biophysics research
and who will give a glimpse into what thenext generation of our society looks like.
For the first time, we have reserved at least
20% of symposia talks for speakers selected
directly from submitted abstracts. Principal
investigators will find the new option to self-

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suggest their abstract describing their latest
research for symposia topics. The topics
will be varied and stimulating, covering thebroad membership of our society. From
staple themes like membrane proteins toventuring into new areas where biophysics
is making an impact, such as plant biology
and how biological systems adapt totemperature change.

https://www.biophysics.
org/2024meeting#

AAES 2024 Annual Meeting
Dallas, Texas
April 20 – 22, 2024

American Association of Endocrine
Surgeons 2024 Annual Meeting attendeesof endocrine surgery. The AAES Annual
Meeting is dedicated to the advancementof the science and art of endocrine
surgery through exchange of knowledge
and fostering collaboration. The upcoming
2024 event promises to deliver innovative

ENDOCRINE ITINERARY

programming that will enrich attendees’ clinicalpractices, provide networking opportunities, andfacilitate scholarly pursuits. We cordially invite you
to join us in Dallas for this exciting event. It will be
an excellent opportunity to dive into new topics,
share expertise, and connect with peers who sharesimilar interests.

https://www.endocrinesurgery.org/2024annual-meeting2024 Lab Manager
Leadership Summit

Denver, Colorado
April 29 – May 1, 2024
The Lab Manager 2024 Leadership Summit willoffer actionable advice on the management,
business, safety, and staffing challenges facing

INTERNATIONAL ITINERARYATTD 2024

Florence, Italy/Virtual
March 6 – 9, 2024
The 17th International Conference on Advanced Technologies & Treatments for
Diabetes (ATTD 2024) is the leading international forum where clinicians, diabetes
care providers, researchers, industries, start-up, investors, reimbursement
authorities, regulators, and people with diabetes, assemble with the goal
to ameliorate the care of people with diabetes at the fastest possible pace.
Presentations and discussions will be given by many distinguished professionals
in the field and will include topics such as artificial intelligence–based decision
support systems, glucose sensors, closed-loop systems, artificial pancreata,devices for diabetes prevention, new medications for the treatment of diabetes,
new insulins and new insulin-delivery systems and pumps, and much more.

https://attd.kenes.com/

World Endocrine, Diabetes & Cardiovascular Conference(EDCC24)
Bangkok, Thailand
March 9 – 10, 2024

The conference program includes local and international speakers with inspiring
insights to share on advancing endocrinology, diabetes, cardiovascular health,and metabolism quality improvement through patient and family experiences.
This will be an opportunity to come together, collaborate, and share the latest
advancements in the endocrinology field, offering the chance to learn andcollaborate across a variety of approaches, disciplines, and specialties, providing
engaging on-demand and live sessions.

https://endocrine.episirus.org/bangkok

Diabetes Meet 2024
Rome, Italy/Virtual
March 11 – 12, 2024
today’s lab managers. The program’s expert
speakers will provide you with the tools youneed to reach higher levels of engagement andefficiency among your lab teams. Topics will
range from dealing with burnout, to incorporating
automation into your lab, to lab operations, toeffective communication, and much more — aninteractive Q&A will follow each session. Attendees
will also be able to participate in hands-on
workshops and roundtable discussions, where they
will receive focused advice and learn from real-life
examples of leadership success.

https://www.labmanager.com/labmanager-leadership-summit-30946

This Diabetes Meet 2024 Conference invites all the academic scientists,
endocrinologists, surgeons, primary healthcare specialists, pediatricians,
pharmaceutical industrial delegates, talented young scientists, and student
communities across the globe to attend this meeting where all the aspects
of diabetes mechanism, disorders, and treatment will be discussed under asingle roof.

https://www.diabetesmeet.com

ECE 2024: 26th European Congress of Endocrinology
Stockholm, Sweden
May 11 – 14, 2024

Attracting over 4,000 delegates, from more than 100 countries, ECE continues
to develop as a world-leading congress for endocrine specialists. Given that
our community works on diverse research topics and sees patients with awide range of conditions, ECE enables access to a comprehensive program,covering the breadth of endocrinology. Whatever your area of interest, there
will be sessions that are of direct relevance, as well as extensive networking
opportunities.

https://www.ese-hormones.org/events-deadlines/europeancongress-of-endocrinology/ece-2024

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |17

BY KELLY HORVATHFor Your
Information

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Recent
Revelations
on Thyroid
CancerTreatment

Thyroid cancer is the most common
endocrine cancer in the world, with morethan 62,000 newly diagnosed cases eachyear in the U.S. alone. Here, we look atsome of the latest research that includes
a study from Endocrine Reviews onradiation-induced thyroid cancer,
a JCEM Case Reports paper on false
positive results in metastatic thyroid
cancer, and a presentation fromENDO 2023 that looks at thyroid
cancer survival.

Three studies from last year delve into some of the nuances ofthyroid cancer, the most common endocrine carcinoma.

One study goes deep into examining the risks of developing
thyroid cancer after radiation exposure, whether due to a planned,
existing, or an emergency situation.
Next, as thyroid cancer is commonly overtreated, often due tounnecessary or overly aggressive thyroid surgery, the second
study examines thyroid cancer surveillance, offering excellent
guidance and potential opportunities on how to personalize
thyroid cancer management, including psychosocial aspects.
Lastly, the third study explores how to improve thyroid cancer
survivorship and the importance of shared decision making
between patient and clinician.

Radiation and Thyroid Cancer
In “Radiation-Related Thyroid Cancer,” from the July 2023 issueof Endocrine Reviews, study authors Vladimir Saenko, PhD, andNorisato Mitsutake, MD, PhD, both from the Department ofRadiation Medical Sciences at the Atomic Bomb Disease Institute

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |19

of the University of Nagasaki in Japan, provide a comprehensive accounting of thyroid
cancer epidemiology, treatment, and prognosis; clinicopathological characteristics; andgenetic alterations from the Chornobyl and Fukushima nuclear power plant accidents.
A new examination of the data from the Fukushima and Chornobyl nuclear disasters
appears to show that radiation-induced thyroid cancers are often more aggressive thansporadic thyroid cancers.

Norisato Mitsutake, MD, PhD“

Medical exposuresto radiation should be
performed carefully,
especially for children.
Much of the evidence
discussed in [our] article
suggests that radiationinduced cancer does
not require special
treatment options,
including bothclinically advanced andlow-risk tumors.”— NORISATO MITSUTAKE, MD, PHD,
DEPARTMENT OF RADIATION MEDICAL SCIENCES,ATOMIC BOMB DISEASE INSTITUTE,
UNIVERSITY OF NAGASAKI, JAPAN“It makes sense to study radiation carcinogenesis in Nagasaki, a city experienced in
atomic bombing,” explains Mitsutake. “On a personal note, I have several relatives who
are A-bomb survivors, so concerns about Fukushima nuclear power plant accident
consequences need to be addressed carefully and scientifically. In addition, there has
been growing concern in recent years about potential attacks on nuclear facilities
and the potential use of nuclear weapons.” These reasons as well as recognizing thatthe peaceful use of radiation must be promoted, such as by the increasing usage ofradioisotopes in the medical field, which exposes patients and medical staff, are what
prompted the authors’ analysis, in view of determining how to reduce thyroid cancer
risk from radiation exposure.
Notably, the Fukushima nuclear accident did not cause thyroid cancer, unlike thatof Chornobyl, because the radiation doses to the thyroid appear to be extremely low
compared to Chornobyl,” Mitsutake says. Risk is dose-dependent and persists for decades
after exposure. “The restrictions on distribution and consumption by the Japanese
government were effective. In addition, residents of the most contaminated territories
were rapidly evacuated or relocated. Again, this decreased their radiation doses.”
They also found that the risk of developing thyroid cancer is not equal, with children being
more susceptible than adults: “For radiation-related thyroid cancer, the radiation doseto the thyroid and younger age at exposure have been identified as etiology-specific risk
factors,” Saenko says. In other words, age at exposure, attained age, and time since exposure
were risk modifiers (but gender was not, despite the presumption that thyroid cancer ismore common in females, which has recently been suggested to be an oversimplification— thyroid cancer is instead more commonly detected in females, while incidence rates at
autopsy were comparable between females and males). “In the Chornobyl thyroid cancer,”he continues, “only stable iodine supplementation was a risk modifier (risk was higher
if there was no supplementation) but not sex, age at exposure, other thyroid diseases, orbody mass index. Iodine sufficiency is also a protective factor that reduces the risk forthyroid cancer from internal irradiation with radioiodine isotopes.”
Regarding the higher radiosensitivity in children, Saenko says that because children havea longer “time to death,” there is more time to observe a long-term consequence from

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a childhood exposure. “Ionizing radiation is largely believed to act as an initiatorof carcinogenesis (delivers the first hit in multistage carcinogenesis). Since there
are more cell divisions, including those of tissue-specific stem cells, in a growing
organism than in an adult, and if such a hit took place during childhood, there isa higher chance that the number of cells carrying a radiation-induced hit (say, acancer-related mutation or an epigenetic change) will become greater.”
Mitsutake has this advice for clinicians: “Medical exposures to radiation should be
performed carefully, especially for children. Much of the evidence discussed in [our]article suggests that radiation-induced cancer does not require special treatment
options, including both clinically advanced and low-risk tumors.” Medically
responsible exposures can be achieved with the “As Low As Reasonably Achievable”(ALARA) principle, which balances the risks and benefits of exposure as well as
considers patient economic and social factors.
The authors call for continued careful research into this area.

False Positives in Metastatic Thyroid Cancer
In “False-positive Imaging for Papillary Thyroid Cancer Caused by Intraosseous
Hemangiomas,” published in JCEM Case Reports last September, researchers
including Stephanie L. Lee, MD, PhD, of the Chobanian & Avedisian School of
Medicine, Boston University, Boston, Mass., describe two patients with papillary
thyroid carcinoma and elevated thyroglobulin (TG) levels, who had false-positive
imaging studies from intraosseous hemangiomas (IH). Despite their similarities,
these cases also had significant differences.
“In case one, the patient had aggressive disease, and his TG level was rising into
the hundreds,” Lee says, “so we knew he had distant metastatic disease. A CT scanof a symptomatic palpable skull mass revealed a lytic skull lesion. Generally, in the
thyroid cancer realm, lytic bone indicates metastatic thyroid cancer.” Due to thispatient’s high risk and the risk of bleeding and infection with biopsying an IH,
especially one located in the skull, the mass was resected and found to be an IH
rather than a metastatic focus of cancer.
In the second case, the patient’s tumor was rated stage I, and her TG level was not
rising, so, as Lee explains it, it did not make sense that this low-risk patient would
have distant metastatic disease, despite her positive radioactive iodine whole-bodyscan showing a focal uptake into a lytic lesion in the skull. The clues that helped themmake an accurate diagnosis were the patient’s history of headaches and a prior MRI

AT A

GLANCEX A new examination of thedata from the Fukushima andChornobyl nuclear disasters
appears to show that radiationinduced thyroid cancers areoften more aggressive thansporadic thyroid cancers.
X Intraosseous hemangioma(IH) can mimic thyroid cancer
metastases in lytic bonelesions and should be partof the differential diagnosis
in patients, but, because no
imaging studies are definitive
for IH, cranial lesions may
warrant resection to establish
a diagnosis and avoid potential
brain invasion by a malignancy
or unnecessary radioiodine
treatment if iodine avid.
X For thyroid cancer survivors,
downstream management
should be tailored to the patient,including when and how to deescalate, as well as supporting
their psychosocial concerns.

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |21

that diagnosed the hemangioma before she had thyroid cancer. That history coupledwith the fact that her lytic lesion stayed the same size in the ensuing two years led theteam to take an inductive approach: “How do we prove this is not cancer so that we don’t
have to do any more diagnostic testing?”

Stephanie L. Lee, MD, PhD“

We don’t usually
think of [intraosseous
hemangiomas] as acause for false positives— it’s actually only
been reported a coupleof times in the distantpast, and so it’s not on
the differential. We rely
on radioactive iodine
whole-body scans todetect metastatic disease.
We all know that there
are false negatives,
especially in tumors thatare not iodine avid ormore aggressive, but
we also need to be awareof the false positives.”— STEPHANIE L. LEE, MD, PHD,
CHOBANIAN & AVEDISIAN SCHOOL OF MEDICINE,
BOSTON UNIVERSITY, BOSTON, MASS.

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A would-be red herring in this case was that this patient had an ectopic thyroid, whichcaused her initially higher-than-expected TG levels. After thyroidectomy, however, her
TG levels did drop to zero, which is what led to the whole-body scan. “This is where wewent down the rabbit hole — but the whole-body scan showed remnant TG levels just in
the thyroid bed and in the lesion in the skull,” Lee says.
“We don’t usually think of IH as a cause for false positives — it’s actually only beenreported a couple of times in the distant past, and so it’s not on the differential,” Lee says.
“We rely on radioactive iodine whole-body scans to detect metastatic disease. We allknow that there are false negatives, especially in tumors that are not iodine avid or moreaggressive, but we also need to be aware of the false positives.” False-positive radioactive
iodine whole-body scans can occur anywhere a protective body of fluid exists, such as
from cysts in the skin or ovaries or from a gallbladder with loculated fluid — anywhere
the radioactive iodine can diffuse in without a specific transporter, becomes restricted
there, and cannot diffuse back out.
This is where IH becomes relevant. The tangle of blood vessels slows blood flow, making
the conditions right for a false positive. “What is unique about IH is that it also can beassociated with false-positive F18-FDG positron emission tomography (PET) imaging.
When you see something that’s iodine avid and PET-positive, you might think that’s
definitely a thyroid cancer. What looks like it’s iodine avid or hypermetabolic is reallyisotope ‘trapping’ rather than specific uptake,” Lee explains. “So, the key takeaway is thatsome false positives in whole-body scans are due to restricted diffusion, and you should
assess the positive scan in the context of the patient’s specific initial and current risk forthyroid cancer recurrence.”That’s why the team felt this case report is important: The false positive occurred in both
high-risk and low-risk patients and, coincidentally, within two years of each other. “Youhave to think about the context of these false positives and what the chances are that itreally is disease and not a falsely positive result. Then you can step back and look at thedifferential of a false positive in the skull, and IH should come up,” Lee says.

Thyroid Cancer Survivorship

Megan R. Haymart, MD, Nancy Wigginton Endocrinology Research Professor in
Thyroid Cancer, and professor of medicine at the University of Michigan in Ann Arbor,presented “Long-Term Management of Patients with Low-Risk Thyroid Cancer” at
ENDO 2023 last June. Her presentation included a series of patient scenarios withrationales gleaned from the literature, including from systematic reviews. As the title
suggests, Haymart’s aim is to characterize optimal, tailored, long-term surveillance,
including when to de-escalate surveillance, and how to improve the quality of thyroid
cancer survivorship.
“We are now in an era of more personalized and tailored management of thyroid cancer,”
Haymart says. “However, there are both advantages and disadvantages to less-intensive
treatment. For example, although surgical risks are greater with more intensive treatment,
the long-term follow-up is more difficult in patients who received less-intensive surgicalor medical management (e.g., less use of radioactive iodine).” Determining the balance
between benefits and risks in the intensity of thyroid cancer treatment and thensubsequent surveillance, she says, requires both clinician and patient input: “For muchof the management of low-risk thyroid cancer, there is a role for shared decision making
between the patient and the clinician with patient preferences incorporated into thedecision-making process.” Long-term surveillance can involve laboratory work-up suchas thyroid-stimulating hormone, thyroglobulin, and thyroglobulin antibody as well asneck ultrasound.
However, although neck ultrasound is an excellent method of follow-up for patientswith thyroid cancer, as it allows detection of structural recurrence, there is a risk of false
positives. In addition, during the surveillance period, patients can experience cancerrelated worry about death, harm from treatment, reduced quality of life, family impact,
and recurrence. Sometimes these worries can be exacerbated by surveillance, especiallywhen there are false positives. “Key to shared decision making,” explains Haymart, “iscommunication about risks and benefits as well as awareness of patient preferences. For
many of the decisions in the management of low-risk thyroid cancer, there are no ‘right-’
or ‘wrong-’ decisions. There is just the decision that is best for that particular patient.”
Although many physicians try their best to address patient worry in the clinic visit,
resources are available outside of the physician-patient relationship that can help, suchas local social workers or psychology or support groups as well as online resources.
“There is more work to be done in helping our patients manage their cancer-related
worry,” Haymart says. “I think this is an area that needs further resources andresearch.”“

Megan R. Haymart, MD

We are now inan era of more
personalized andtailored managementof thyroid cancer.
However, there areboth advantages anddisadvantages toless-intensive treatment.
For example, althoughsurgical risks are greaterwith more intensive
treatment, the longterm follow-up is moredifficult in patients who
received less-intensive
surgical or medical
management (e.g., less useof radioactive iodine).”— MEGAN R. HAYMART, MD,
NANCY WIGGINTON ENDOCRINOLOGY RESEARCH
PROFESSOR IN THYROID CANCER;
PROFESSOR OF MEDICINE,
UNIVERSITY OF MICHIGAN, ANN ARBOR, MICH.

– HORVATH IS A BALTIMORE, MD.-BASED FREELANCE WRITER. SHE WROTE AND
RESEARCHED THE MASSIVE “EUREKA 2023” IN THE DECEMBER ISSUE THATHIGHLIGHTED THE TOP ENDOCRINE DISCOVERIES OF THE YEAR.
ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |23

Getting Back to

NORMAL:

Options for Treating Hypoparathyroidism
Endocrine News talks to Aliya Khan, MD, about the debilitating
effects of hypoparathyroidism, new treatment guidelines shehelped create, and exciting news from trials that showedpromising results that could allow these patients to have a muchimproved quality of life, both physically and psychologically.
BY DEREK BAGLEY

24 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

Due to his idiopathic hypoparathyroidism, a patient of Khan’s couldn’t even go
swimming or have a driver’s license since he was prone to seizures due to having
abnormal calcium levels. However, that has all changed since the young man has
been a part of the phase 3 PaTHway Trial of palopegteriparatide, an investigational
prodrug with sustained release of active parathyroid hormone (PTH [1-34])
administered once daily.

“Iwish I had this medicine when I was a kid,” a young patient withhypoparathyroidism tells his endocrinologist, Aliya Khan, MD, FRCP, FACP,
professor of clinical medicine at McMaster University in Ontario, Canada,
as he participates in a clinical trial investigating a prodrug that replaces parathyroid
hormone (PTH). Because of his condition and subsequent treatment, this young man
experienced calcium fluctuations so severe that he experienced frequent seizures due
to low serum calcium. Because of the seizures, he had difficulty concentrating and was
unable to finish school. He couldn’t drive; he couldn’t even go swimming. He also hadrecurrent kidney stones and was often hospitalized.
“If you can’t drive, you can’t get to work or you’re dependent on someone else,” Khansays. “If you’re having seizures and you don’t know when you could have a seizure, that
affects your ability to swim or do sports activities that other people take for granted
because they know they’re not going to have a seizure. He could have a seizure if he wasswimming. What if he had a seizure and he died in the pool?”
The young man is participating in the ongoing Phase 3 PaTHway Trial of
palopegteriparatide, an investigational prodrug with sustained release of active
parathyroid hormone PTH (1-34) administered once daily. Ascendis Pharma is funding
the trial of TransCon PTH and marketing the drug as Yorvipath®.

Aliya Khan, MD

Khan presented 52-week data from the open-label extension period of the trial at theAmerican Society for Bone and Mineral Research (ASBMR)’s 2023 in Vancouver last
October, showing that adults with chronic hypoparathyroidism, whose bones tend tobe over-mineralized due to insufficient parathyroid hormone-(PTH)-exposure, trended
toward a new skeletal steady state closer to age-appropriate norms with continued useof TransCon PTH. The results were consistent regardless of sex, menopausal status, or
duration of disease and were consistent with results previously reported through Week
110 in the Phase 2 PaTH Forward Trial.
“When we put him into this study, it was like a new person walked in,” Khan says. “He
said, ‘I haven’t had to go to the hospital. I haven’t had any more seizures. And guess
what? I haven’t had any more kidney stones.’”Khan says that the young man has idiopathic hypoparathyroidism, and he has had
symptoms since he was a child – basically being unable to function because his calcium
levels weren’t normal. “Now he’s saying, ‘I feel that I missed out on my education, but
now that my calcium levels are stable and they’re normal, and I don’t need to worry

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |25

Until very recently, many hypoparathyroidism patients were treated withcalcium (bottom) and vitamin D (top). However, since that treatment
can elevate phosphate levels, it increases the risk of myriad long-term
debilitating complications.

about having a seizure,’ and he’s getting his driver’s license and he’sin university,” she says. “It’s a life-changing event to be able to restore
normal, or as close to normal as possible, parathyroid function that weare able to provide at this time with modern medicine.”

Myriad Impacts
Until very recently, patients with hypoparathyroidism were treated withactive vitamin D and calcium, but that treatment can increase the riskof long-term complications because it can further elevate phosphate,
which can cause calcium and phosphate to deposit in the brain, behindthe eyes, and in the kidneys, which can cause nephrocalcinosis, withthe whole renal parenchymal calcifying.

“

I think that we’ve beenable to make an impact on
the diagnosis and awareness[of hypoparathyroidism].
Endocrinologists are aware andobviously know how to makethe diagnosis, but primarycare physicians may not haveconsidered the possibility
that someone’s calcium could be
low, especially in young people
who haven’t had any medical
problems so far.”— ALIYA KHAN, MD, FRCP, FACP, PROFESSOR OF CLINICAL MEDICINE,
MCMASTER UNIVERSITY, ONTARIO, CANADA

26 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

Khan says that 95% of participants in this current clinical trial wereable to come off of vitamin D, while stabilizing calcium and bonedensity with palopegteriparatide. “This is really reassuring data, andit’s nice to be able to replace PTH, be able to normalize calcium levels,
be able to correct the urine calcium, correct the phosphate levels, andimprove quality of life,” she says. “We’ve seen significant data showing
improvements in quality of life and bring bone remodeling and thebone density values similar to the age-matched and gender-matchednorms.”
Reflecting on the clinical 52-week data on palopegteriparatide andits potential impact, Khan says, “Treatment with TransCon PTH in
this clinical trial showed the positive physiological effects on bone inpatients treated for the full year as well as in those switching fromplacebo after the 26-week blinded period. These results underscorethe importance of providing the missing hormone to address thesignificant impacts of hypoparathyroidism, including decreased bone
remodeling leading to a dense, over-mineralized bone structure.”
And again, the impacts of hypoparathyroidism — and its treatment— are significant for the patients and their families. Khan says it’s
important to look at the complications of hypoparathyroidism,
because it affects so many systems — vision, kidneys, lungs, heart,
even mental health. “All of these need to be evaluated,” she says,“Physicians need to look at that, and we need to also ask, ‘How is it
affecting you? And not just you personally, but your job, your school,
your education, your family? What if you’ve got kids? How are youable to handle your kids?’”

Khan says she treats young mothers with hypoparathyroidism who have just hada baby, and newborns aren’t exactly known for sleeping through the night. “It’svery difficult,” she says “We need to recognize the impact on the person and theirfamily and their whole situation. Look for the multi-system complications, including
skeletal complications, renal complications, and neurologic complications, andensure that we’re addressing all of those.”
Khan is happy to report that palopegteriparatide has improved patients’ mental
health as well. “And their social function,” she says. “It’s definitely making an impact
on clarity of thinking, their ability to concentrate, their mood, their functioning.
We know that it’s not just calcium that’s important for brain function. We also know
there are PTH receptors in the brain, so if we give back PTH, we’re giving backthe missing hormone that’s affecting brain function and cognition, and those are all
critical aspects that need to be addressed.”“Valuable Treatment Options Available”
Khan presented 26-week data from the Phase 3 PaTH Trial at ENDO 2022, as well as
Clinical Endocrinology Update (CEU) that same year, with a talk titled “Diagnosis
and Management of Hyperparathyroidism & Hypoparathyroidism,” in which she

AT A

GLANCEX Hypoparathyroidism can bea debilitating disorder, andtreatment can increase the riskof long-term complications andis difficult to follow due to thevery large number of calcium
and active vitamin D pills needed
every day.
X Clinicians are investigatinga prodrug that replaces
parathyroid hormone in patientswith hypoparathyroidism, andthe results so far have beenpromising.

Although relatively rare, hypoparathyroidism occurs when the body produces
abnormally low levels of parathyroid hormone (PTH), which regulates the levelsof calcium and phosphorus in the body. Khan says it’s important to look at thecomplications of hypoparathyroidism, because it affects so many systems – vision,
kidneys, lungs, heart, and mental health.

X Clinicians should be up todate on the latest guidelines,
published in late 2022.
Conventional treatment remains
the first-line therapy, but
PTH should be considered if
conventional therapy fails.

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |27

“

We know that it’s
not just calcium that’s importantfor brain function. We also
know there are PTH receptors inthe brain, so if we give back PTH,
we’re giving back the missing
hormone that’s affecting brain
function and cognition, andthose are all critical aspects
that need to be addressed.”— ALIYA KHAN, MD, FRCP, FACP, PROFESSOR OF CLINICAL MEDICINE,
MCMASTER UNIVERSITY, ONTARIO, CANADA

pointed to new drug agents like palopegteriparatide as a welcome
alternative to conventional therapy, since, again, that treatment
can only compound the problem. “We want to improve patients’
well-being from day to day, and we can normalize calcium withcalcium and active vitamin D, but we’re not helping the long-term
complications with conventional therapy,” she told Endocrine News
ahead of her CEU presentation. “And if we’re making that likelihoodof chronic kidney disease earlier and more severe, then we’re notreally helping our patients.”
Khan says that since her presentations in 2022 and 2023, she sees
improved awareness among providers, where there might have beensome knowledge gaps before. Hypoparathyroidism can be easy to
dismiss as anxiety for a physician who might not be up to date with
the new recommendations and guidelines. “I think that we’ve beenable to make an impact on the diagnosis and awareness,” she says.
“Endocrinologists are aware and obviously know how to make thediagnosis, but primary care physicians may not have considered thepossibility that someone’s calcium could be low, especially in young
people who haven’t had any medical problems so far.”
Khan and her co-authors published the updated guidelines for theevaluation and management of hypoparathyroidism in November
and December 2022 — 17 articles across two volumes in ASBMR’s
Journal of Bone and Mineral Research. “We went crazy,” she laughs.
The three key highlights from the guidelines are: diagnose thecondition as early as possible, understand what the cause is (idiopathic
or postsurgical), and treat according to the guidelines. “You can startwith conventional therapy and monitor patients closely,” she says.
“And if you’re making changes in their management, make smallchanges with close follow-up. Don’t make big changes and then not
see them for three months. They’ll end up in the ER. Small changes
with closer follow-up."“And if they’re not doing well,” Khan continues, “if their calcium
levels are fluctuating, their cognition is poor, and they’re having
complications or kidney stones or decline in renal function, switch
to PTH, and don’t neglect the fact that we do have valuable treatment
options available.”– BAGLEY IS THE SENIOR EDITOR OF ENDOCRINE NEWS. IN THE NOVEMBER ISSUE, HE WROTE
ABOUT POTENTIAL PHARMACOLOGICAL OPTIONS FOR PREVENTING DIABETES.

28 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

NEWBone Health Toolkit andOsteoporosis Guideline App
Emerging Therapies in Osteoporosis
E X PA N D Y O U R T R E AT M E N T O F O S T E O P O R O S I S
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Educational
materials

EARLY-CAREER CORNER

standardized
testing
BY DEREK BAGLEY

P

riyanka Majety, MD, assistant professor in the Division
of Endocrinology, Diabetes, and Metabolism at
Virginia Commonwealth University in Richmond,
vividly remembers seeing a patient with a family history of
thyroid cancer, who presented with a sub-centimeter thyroid
nodule, in her training.
When the team input the patient’s history and ultrasoundfindings into different risk-stratifying tools, therecommendations about next steps varied, based on thetool used. Some tools recommended no biopsy; others
recommended considering a biopsy or monitoring the nodulewith a repeat ultrasound after a certain interval.
“After a detailed discussion with the patient, and given her
family history of lethal thyroid cancer, at her request, we
biopsied the nodule, which turned out to be malignant,”
Majety says. “She underwent surgery and is doing
well, but this case highlights the discrepancy between
recommendations, based on the inclusion or exclusion ofclinical features and variability in ultrasound size cut-offs
informing guidance regarding biopsy.”
About half the population will develop a thyroid nodule byage 60; up to 90% of these are benign. Most thyroid cancers
are low-risk neoplasms that usually do not have an impact
on survival. Diagnosing and treating these include not only aphysical examination but also an ultrasound of the nodule(s),followed by a biopsy, which can have a detrimental effect on

30 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

With thyroid cancer patients often getting different — andsometimes conflicting — treatment recommendations from a variety
of diagnostic tools, Priyanka Majety, MD, talks to Endocrine News
about why it’s time for clinicians to coalesce around a single setof standards for these cases, which could potentially eliminate
unnecessary procedures.

Evaluating patientswith suspected thyroid
nodules must include
a thorough medical
history and physicalexamination, a thyroidstimulating hormone(TSH) level, andultrasound, as shown
here, which determines
nodule size, allowing
providers to estimate
the risk of these nodules
being malignant.

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |31the patient’s emotional and financial status. Majety saysthat in the U.S., more than 500,000 fine-needle aspirations(FNAs) are done each year, and about 200,000 of them turnout to be unnecessary.

“

Priyanka Majety, MD

There is a strong need for auniversal RSS with a lexicon toharmonize all the current systems
and standardize the evaluationof thyroid nodules with the aimof reducing unnecessary thyroid
biopsies without jeopardizing thedetection of clinically significant
malignancies. Until this ideal
tool is developed, clinicians
should continue to use the tools
available and individualize
the management based on
individual risk factors.”— PRIYANKA MAJETY, MD, ASSISTANT PROFESSOR,DIVISION OF ENDOCRINOLOGY, DIABETES, AND METABOLISM,
VIRGINIA COMMONWEALTH UNIVERSITY, RICHMOND, VA.

32 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

A Need for Uniformity
According to Majety, evaluation of patients with suspected
thyroid nodules must include a thorough medical history
and physical examination, a thyroid-stimulating hormone(TSH) level, and ultrasound evaluation. Based on the sizeof the nodules and other characteristics on ultrasound,providers estimate the risk of these nodules being
malignant.
To stratify the risk of malignancy, various tools areavailable, but there are considerable differences among
these tools — they differ in their formats (patternrecognition versus point systems), risk categories, FNA
size thresholds, and recommended surveillance intervals.
Multiple studies have compared various risk stratification
tools, and no single system has consistently demonstrated
superiority over the others.
“It is important to identify the nodules at the highest risk ofmalignancy,” Majety says. “Currently, there are several risk
stratification tools including clinical practice guidelines,
scoring systems, web-based calculators, and an interactive
algorithm, available to clinicians. This poses a uniquechallenge to not just the clinicians but also the patients, due
to the lack of uniformity in the recommendations.”
In June 2023, Majety’s paper, “Thyroid Nodules: Need for a
Universal Risk Stratification System” appeared in a special
issue of Frontiers in Endocrinology, “Thyroid Nodule
Evaluation: Current, Evolving and Emerging Tools.” Theissue highlighted the challenges faced by clinicians inthis field, and how those challenges are currently being
addressed.

EARLY-CAREER CORNER

Majety writes that using multiple risk-stratifying systems(RSSs) can lead to confusion at times. The varied RSSs canaffect clinicians in training, as well, since their attendings
may have different approaches. She explains that radiologists
and endocrinologists typically use different guidelines
for risk stratification, which can lead to unnecessary time
consumption, as physicians have to re-review those nodules
and stratify risk using a different tool.
“Endocrinology fellows in training tend to work withseveral teaching attendings, and many of them have a
different approach to thyroid nodule evaluation, the biggest
difference being the RSS in use,” Majety says. “Some of thesenior physicians tend not to use any system but go with
their intuition, while other physicians use different systems,
reflective of the differences in their training and experience.
It can sometimes be an overwhelming and confusing
experience.”

Reducing Unnecessary Biopsies
Currently, there are several RSSs across the globe, varying by
country and professional organization, and clinicians choose
which tool to use based on geography and specialization.
There are other RSSs that are developed by groups ofinvestigators who do not represent any professionalorganization. “It is a huge undertaking to bring all the
professional societies together and develop a universal RSS
that they all agree upon,” Majety says. “Even if one such
universal tool is developed, it would still need to be validated
in large, multi-regional population studies before clinicians
can use it.”For Majety, her ideal RSS would minimize the number of
unnecessary biopsies and identify all clinically significant
thyroid cancers, leading to lower healthcare costs andmorbidity. “The goal is to develop a universal risk
stratification system that identifies all clinically significant
thyroid cancers and that would help not only clinicians
but also patients in understanding ultrasound reports andmaking appropriate recommendations in identifying thenodules that require further evaluation including a biopsy,”
she says.
Majety points to a grassroots initiative, managed by thesteering committee of the International Thyroid Nodule
Ultrasound Working Group (ITNUWG), is currently
working to develop an international system, termed
I-TIRADS, that integrates the leading risk-stratifying
systems.
“There is a strong need for a universal RSS with a lexicon
to harmonize all the current systems and standardize theevaluation of thyroid nodules with the aim of reducing
unnecessary thyroid biopsies without jeopardizing thedetection of clinically significant malignancies,” Majety
continues. “Until this ideal tool is developed, clinicians
should continue to use the tools available and individualize
the management based on individual risk factors.”

Another major challenge, Majety says, of ultrasound-based
RSSs is the inter- and intra-observer variability. There
are still inconsistencies in thyroid ultrasound examiners’
reporting and rating abilities. “One potential solution to allthese challenges is a unified lexicon of thyroid ultrasoundfeatures and dedicated training,” she says.
– BAGLEY IS THE SENIOR EDITOR OF ENDOCRINE NEWS. IN THE NOVEMBER ISSUE, HE
WROTE ABOUT POTENTIAL PHARMACOLOGICAL OPTIONS FOR PREVENTING DIABETESENDOCR INE NEWS | JA N UA RY 2 0 2 4 |33

PRACTICE RESOURCES

Molecular Testing
and the Future of
Diagnosing Thyroid Cancer

BY KELLY HORVATH

Endocrine Society member and medical director for
Endocrinology for Veracyte, Joshua Klopper, MD, talks to
Endocrine News about a new tool that may have the potential
to guide thyroid cancer management decisions by predicting
tumor behavior via molecular signatures.
34 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

PRACTICE RESOURCES

I

n “New Data Presented at the 2023 ATA Annual
Meeting Demonstrate that Veracyte’s Afirma-Based
Testing Can Uncover Key Molecular Hallmarks ofThyroid Cancer,” published online in Business Wire lastSeptember, Joshua Klopper, MD, medical director for
Endocrinology for Veracyte, a genomic technology company
specializing in cancer diagnostics, explains what novel
molecular insights for thyroid nodules and cancer are
enabled by preoperative analysis with the Afirma Genomic
Resource for Intelligent Discovery (GRID), a researchuse-only tool that is derived from the company’s Afirma
Genomic Sequencing Classifier (GSC).
“The fundamental difference between the Afirma molecular
testing platform and any other commercially available
testing platform is the whole transcriptome–derived assay.
As opposed to a panel of genes or a panel of microRNAs,
almost everything that is expressed as mRNA is sequenced
with Afirma GSC,” Klopper says. “We strongly believethat assessing mRNA and what is transcribed is the bestindicator of what’s going on because a mutation that may beseen in DNA can sometimes be silenced. We’re sequencing
everything that’s expressed out of those genes, so we’resitting on a huge treasure trove of molecular data, not onlywith each nodule but with our entire database. We believe
this resource can enable new discoveries to help advancecare for patients with thyroid nodules and cancer.”
Veracyte’s data and analytics team can then cultivate novelsignatures and report the different genes that are expressedby carving them out of the database. “So, GRID — it’s in thename — it’s a resource. Our expectation is that it will expand
over time,” Klopper says.

Potential Treatment Stratification
Afirma GRID is modeled on the company’s Decipher
GRID tool that has been used in prostate cancer research

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |35

“We strongly believe that assessing mRNA and what istranscribed is the best indicator of what’s going on because amutation that may be seen in DNA can sometimes be silenced.
We’re sequencing everything that’s expressed out of thosegenes, so we’re sitting on a huge treasure trove of molecular
data, not only with each nodule but with our entire database.”

Joshua Klopper, MD— JOSHUA KLOPPER, MD, MEDICAL DIRECTOR FOR ENDOCRINOLOGY, VERACYTE, DENVER, COLORADTS

since 2015 and includes more than 400 gene signatures.
Klopper says they hope to do for thyroid cancer researchwith Afirma GRID what Decipher GRID is doing forprostate cancer research. “We’re not quite there yet, but theposters we presented at the American Thyroid Association
demonstrated different potential aspects of what can beprovided by doing this whole transcriptome–derived
analysis,” he adds.
For example, with the “Sodium Iodide Symporter (NIS)
Expression in Cytologically Indeterminate and Malignant
Thyroid Nodules” poster, Prasana Santhanam, MBBS, MD,from the Johns Hopkins University School of Medicine andteam analyzed over 47,000 thyroid nodules and demonstratethat NIS gene expression is differentially expressed based on

the presence of molecular variants, such as high expression
in thyroid nodules with a TSH receptor variant and lower
expression in nodules with a BRAF V600E mutation.
Additionally, they show that NIS expression declines as
thyroid tumors become increasingly more oncocytic andneoplastic.
Because NIS activity is required for radioactive iodine
uptake, these findings can potentially aid in the treatment
and monitoring of differentiated thyroid carcinomas
when radioiodine therapy is indicated. “We can report
the NIS expression level and seek differences among thedifferent kinds of nodules and different mutations,” Klopper
says, which may ultimately lead to potential treatment
stratification.

Promising New Approach?
The “Leveraging RNA Sequencing for
Pre-Operative Immunophenotypingof BRAFV600E+ Thyroid Nodules”
poster from Jarod Olay, MS, fromthe UCLA David Geffen Schoolof Medicine and team likewiseoffers a promising new approach topreoperative assessment of thyroid
tumors.
The team performed a retrospective
analysis of nearly 48,000 thyroid
nodules. “We know that the immune
system can promote or inhibit
cancer responsiveness,” Klopper
says. The findings suggest that theAfirma GRID immunophenotype

36 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG

PRACTICE RESOURCES

gene expression may one day help predict thyroid cancer
response to immune checkpoint inhibitor therapy using
preoperative immunophenotyping rather than postoperative
immunohistochemistry.

of this platform allows us to find and/or create novelsignatures,” Klopper explains.

In the “Molecular Assessment of Isthmus Thyroid
Carcinomas” poster, Endocrine Society member Sina Jasim,
MD, from Washington University in St. Louis, Mo., andteam started from the well-described data that cancers of the
thyroid isthmus tend to have a higher risk of malignancy andmore aggressive behavior than do lobar cancers and teasedout some of the different molecular signatures occurring
there.

In summary, Klopper says, “Analyzing whole transcriptome–
derived RNA sequencing provides a wealth of information.
For the Afirma GSC test, we use this data to create benign
and suspicious classifiers as our primary output, and they’re‘trained to the truth’ — whether cancer is present or not.”These signatures, such as follicular to mesenchymaltransition, provide mechanistic evidence of diagnostic andprognostic differences between isthmic and lobar tumors.
Ultimately, using this molecular data may influence how
isthmic thyroid cancer is managed. “The unique aspect

Contrary Tumor Behavior

As we look toward the future when molecular testing canprovide prognostic information, it must be recognized thateven with the same mutation, thyroid cancers can behave
very differently, so having additional molecular data may
help clinicians provide more personalized care. Afirma
GRID is a research-use-only tool that can allow for studies
that analyze prognostic information beyond the presence ofmolecular variants and fusions.

REA CH THE WORLD WITH YOUR WORKP U B L I S H

I N

E N D O C R I N E

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J O U R N A L S

For more information about publishing with the Endocrine Society, please visit
academic.oup.com/endocrinesociety.

© 2024 ENDOCRINE SOCIETY

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |37

ADVOCACY

Endocrine Society
2023 Advocacy Accomplishments

T

he Endocrine Society is advocating for you. In 2023 weachieved several important advocacy accomplishments,
including:u Making insulin more affordable;u Advancing legislation to allow Medicare to cover antiobesity medication;

u Increasing Medicare physician payments for endocrinology;
u Expanding telehealth coverage;u Protecting access to gender-affirming care;u Protecting the National Institutes of Health from budget
cuts;

u Influencing the development of a global plastics treaty
All these accomplishments were achieved because our members
participated in our advocacy activities, online campaigns,
Hill Days, and meetings with policymakers. Below are someexamples of our advocacy victories.

Advocacy to Lower the Cost of
Insulin — The Endocrine Society is one of
the leading voices calling for U.S. legislation tolower the cost and price of insulin. Our work
has influenced the Biden Administration toprioritize this issue and Congress to develop
legislative proposals.

uMedicare Insulin Price Cap:Historic legislation was signed into law
capping the out-of-pocket cost of insulin at

38 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG$35 per month for people with
Medicare. The legislation wasa long-term goal of the Society
and is a monumental moment in
the history of diabetes advocacy.

u Congressional

Meetings &Briefings: The Endocrine
Society has conducted hundredsof congressional meetings tourge passage of bipar tisan
legislation and conducted
several educational briefings
for policymakers about insulin
affordability.

u White House Action: The Endocrine Society met with
the Biden Administration to make insulin affordability
a priority. As a result, a proposal to expand an insulin copay cap to the private insurance market was included in thepresident’s budget and in the State of the Union address.

Reducing the Prevalence of Obesity — The
Endocrine Society is working to reduce the prevalence of obesityin the United States by educating Congress about obesity andidentifying policy options that would address this issue.

u Obesity Playbook: Early in 2023, the Endocrine Society
published an educational resource for members of Congress
and their staff about obesity. The Playbook was designed to
be a “go-to” resource for members of Congress and theirstaff when they answer constituent questions about obesityand consider legislation related to obesity. The Obesity
Playbook contains data on obesity prevalence, the economic
cost of obesity, obesity’s impact on military readiness, policy
options to address obesity, and a list of Society members

ADVOCACYIn April 2023, Endocrine Society PastPresident, Carol Wysham, MD, and President
Steve Hammes, MD, PhD, joined a groupof Endocrine Society members to advocate
for $50.92 billion for the NIH and call attention
to endocrinology’s key role in diabetes research.

Advisors to the Current Procedural Terminology (CPT)
Committee. Chase Hendrickson, MD, MPH, Sandhya
Chhabra, MD, Allan Glass, MD, and Ricardo Correa, MD,represent the Endocrine Society at the RUC and CPT.
who are experts in the field. Endocrine Society members
Drs. Amy Rothberg, Rocio Pereira, and Jami Josefson served
as advisors for the Playbook.

u Congressional Briefings: The Endocrine Society conducteda Congressional briefing for members of Congress andtheir staff to educate them about prevalence of obesity, its
financial costs to our healthcare system, and its impact
on America’s military readiness. Endocrine Society
members Drs. Amy Rothberg and Ricardo Correa spokeat the briefing, highlighting new data from the CDC about
increasing obesity prevalence and its impact on our military.

u Treat and Reduce Obesity Act: The Endocrine Society has
been collaborating closely with the sponsors of the Treat andReduce Obesity Act (TROA) on the bill’s reintroduction.
TROA is a bipartisan bill that would improve Medicare
coverage of various treatments for obesity, including antiobesity medications. Improving access to obesity treatments
is a top priority for the Society.

Improving Medicare Physician Payment — The
Endocrine Society advocates to increase physician payment torecognize the value endocrinologists bring to the healthcare
system.

u Averting Medicare Cuts: Endocrine Society advocacy
resulted in averting significant Medicare physician payment
cuts in 2023 and 2024. We continue to call on Congress toimprove the Medicare physician payment system.

u Improving Coverage and Coding: Endocrine Society
advocacy includes representation at the American Medical
Association’s Relative Value Update Committee (RUC) andu Expanding Access to Telehealth: Endocrine Society
successfully advocated for a two-year extension of thetelehealth waivers put in place during the COVID-19 Public
Health Emergency, ensuring that our members can provide
care to patients via telehealth.

u Telehealth Policy Perspective Paper: The Society publisheda telehealth policy perspective in JCEM that provides
guidance to Endocrine Society members on the appropriate
use of telehealth in endocrinology.

Protecting Access to Gender-Affirming Care
— The Endocrine Society advocates to expand, improve,and protect access to care for transgender and genderdiverse individuals. We do this by providing information topolicymakers, courts, and the public about gender dysphoria/
gender incongruence and evidence-based medical treatment
options.

u Friend of the Court: The Endocrine Society has
submitted “friend of the court” briefs (also known asamici briefs) in court challenges to state laws that ban
gender-affirming care or criminalize the physicians
who provide it. We work with respected medical, mental
health, and healthcare organizations to submit an amicus
brief to the Court with medical evidence supporting thestandard of care for treating transgender and gender
diverse individuals.

u Strengthening AMA Policy: The Endocrine Society led
a historic effort to protect access to gender-affirmingcare at the annual meeting of the American Medical
Association (AMA) House of Delegates. The Endocrine
Society introduced a resolution that would call on the

ENDOCR INE NEWS | JA N UA RY 2 0 2 4 |39

ADVOCACYAMA to oppose any criminal and legal penalties against
patients seeking gender-affirming care, family members
who support them in seeking medical care, and healthcare
facilities and clinicians who provide gender-affirming care.

by proposed broad cuts to public health programs, including
biomedical research.

u Advanced Research Projects Agency for Health(ARPA-H): The Endocrine Society was invited to present at
two different listening sessions by the Biden administrationand discuss how the new agency could benefit endocrinerelated science. The Society also urged policymakers
to ensure funding for ARPA-H would supplement, notsupplant, funding for NIH.

u Voice of Science in Public Discourse: The Endocrine
Society represents the voice of science in discussions abouttransgender health and treatment for gender dysphoria/
gender incongruence. The Endocrine Society was featured
on an episode of The Problem with Jon Stewart that focusedon access to gender-affirming care. Stewart interviewed
Endocrine Society clinical practice guideline author Josh
Safer, MD, to discuss the medical evidence supporting
gender-affirming care for minors. This episode was widely
praised for combatting the misinformation about genderaffirming care.

u Congressional Hill Days: The Endocrine Society sponsors
regular Capitol Hill Days, during which our members meetwith congressional offices to discuss NIH funding. In 2023,
our Past-President, Carol Wysham, and our President Steve
Hammes, joined a group of Endocrine Society members to
advocate for $50.92 billion for the NIH and call attention
to endocrinology’s key role in diabetes research. We also
lend our voice in the research community’s annual Rally for
Medical Research Hill Day, calling on Congress to increase
funding for biomedical research.

Advocacy to Increase
Funding for the NIH— Funding for the National
Institutes of Health (NIH) isa top priority of the Endocrine
Society. Our goal is to protect
the NIH from funding cutsand to ensure that all NIH
institutes receive significant
f u nd i ng i nc re a s e s a s aproportionate share of a total
increase. We also advocate
for special attention to early
career scientists and to reduce
administrative burdens on scientists. In addition, we raise thevisibility of endocrine-related research and researchers.

Global Advocacy for Better EDC Regulation — The
Endocrine Society is the voice of science in policy discussions
around the globe concerning endocrine-disrupting chemicals(EDCs). As a result of our work, policymakers now recognize
EDCs as a hazardous class of chemicals, support research thatstudies environmental exposures and their impact on humanhealth and are developing legislation and regulations to better
regulate EDCs.

u Scientific Statements on

u Advocacy Campaigns: We are asking members to urge theirlawmakers to support increased NIH funding. Congresscurrently is considering funding for fiscal year (FY) 2024,
which officially began October 1, 2023. The Society has beena vocal advocate for not only increasing NIH funding, butalso averting a federal shutdown and protecting against
proposals and amendments to cut funding.

u Testimony: The Endocrine Society provides annual testimony
to the Appropriations Committee recommending funding
levels for the NIH. In 2023, we highlighted the dangers posed

40 | JA N UA RY 2 0 2 4 | ENDOCR INENEWS.ORG.

EDCs: The Endocrine
Society was the firstscientific organization todevelop a statement on
what the science tells us
about EDCs and makepolicy recommendations.
E nd o c r i ne
Societ ymember Andrea C. Gore,
PhD, led this effort.

A Health eCareers Partneru Estimates of the Costs of Health Effects from EDCs: The
Endocrine Society was the only scientific organization to
publish the estimated cost of health effects from EDCs. This
work grabbed the attention of policymakers in the EU
and continues to drive action. Endocrine Society member
Leonardo Trasande, MD, MPP, conducted the study.

u Use of Science in Regulatory Decisions: The Endocrine
Society routinely submits the latest scientific evidence toregulatory agencies to ensure that regulations are based
on up-to-date knowledge of the effects of chemicals on
endocrine systems. In 2023, we influenced a decision madeby the European Food Safety Agency to lower the exposure
limits to bisphenol A in food.

u Plastics Treaty Negotiations: The Endocrine Society is aleading scientific voice in United Nations negotiations todevelop an international treaty to end plastic pollution.
Marina Fernandez, PhD, has spoken during plenary
sessions and throughout the treaty process to ensure that
health-focused objectives, including measures to reduce
exposure to EDCs in plastic, are included in the treaty.

u Advising the European Commission on Legislation

to Implement the EU Ambition for a “Toxic-Free”
Environment: The Endocrine Society holds a positionon the group advising the EU Commission. Endocrine
Society member Anne-Simone Parent, MD, PhD
represents the Society.

For up-to-date information on our advocacy work and to learn
how you can participate, please visit endocrine.org/advocacy
or contact us at advocacy@endocrine.org.

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