#470 Thyroid Nodules and Thyroid Cancer for Primary Care

Summary

The Curbsiders Internal Medicine Podcast

Episode #470: Thyroid Nodules and Thyroid Cancer for Primary Care

Release Date: February 10, 2025
Guests: Dr. Kaniksha Desai (Stanford University) & Dr. Ana Chindris (Mayo Clinic Florida)

Overview

In this episode, Drs. Matthew Watto and Paul Williams interview thyroid experts Dr. Kaniksha Desai (Stanford) and Dr. Ana Chindris (Mayo Clinic Florida) about the evaluation and management of thyroid nodules and thyroid cancer in the primary care setting. They cover updated approaches to incidental thyroid nodules, the workup process, risk stratification, interpreting imaging and biopsy findings, recent shifts in thyroid cancer management, and how to address new controversies—such as the use of GLP-1 agonists in patients with a thyroid cancer history. The conversation balances practical takeaways with up-to-date evidence and expert insights, aiming to empower primary care clinicians.

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Meet the Guests [03:25–08:46]

• Dr. Kaniksha Desai: Endocrinologist, Stanford University; specializes in thyroid nodules & cancer, board certified in neck ultrasonography.
• Dr. Ana Chindris: Endocrinologist, Mayo Clinic Florida; focus on thyroid neoplasia; treasurer, Florida Endocrine Association; researcher and orchid enthusiast.

Memorable Moment:

• Dr. Chindris discusses her passion for Formula 1 racing since medical school — and vanda orchids.
• Dr. Desai shares key career advice:

  "Take the best of what everybody has to offer and then create your own style... keep an open mind about what's possible. Nothing is impossible." [06:49]

---

Case 1: Evaluating an Incidental Thyroid Nodule [08:55–23:25]

Scenario

• 68-year-old male (“Mr. Ty Rad”) with thyroid nodules found incidentally on lung cancer screening CT.

Initial Approach

• Incidental thyroid nodules are highly common. Most are benign, especially as age increases.
• Start with two key questions:
  • Is the nodule benign or malignant?
  • Is the nodule causing symptoms?

History & Exam Points

• Ask about:
  • Family history of thyroid cancer
  • Personal history of childhood or whole-body radiation (esp. Chernobyl exposure, bone marrow transplant)
  • Local symptoms: neck tightness, dysphagia (solids > liquids), breathing difficulty (esp. supine)
  • Subtle symptoms of hyperthyroidism (e.g., personality change, palpitations, heat intolerance)
  • Examine for palpable mass, cervical lymphadenopathy, tracheal deviation
• Physical Exam Pearls:
  • It’s normal to not palpate nodules <1 cm or posterior ones, even if ultrasound sees them
  • Styles vary: behind the patient (classic), but “there are many different styles.” — Dr. Desai [21:10]
  • Tip: “Just tell the patient you’re going to be grabbing their neck…” [22:17]

TSH and Imaging

• TSH is sensitive; if borderline low, monitor for developing hyperthyroidism (can fluctuate)
• Ultrasound is the gold standard and should be obtained for all new nodules
• Nuclear medicine scans (radionuclide) are rarely needed except for workup of overtly hyperfunctional (toxic) nodules, or when surgery is considered for a toxic nodule [23:25–28:33]

“I personally order an ultrasound in everybody.” – Dr. Chindris [23:25]

---

Laboratory Workup and Special Tests [28:33–34:01]

Typical Labs

• TSH is usually sufficient unless hyperthyroidism is suspected; T4/T3 rarely needed if TSH normal.
• Calcitonin: Only order if there’s a strong suspicion for medullary thyroid cancer (family history, RET mutations, men2 syndrome) — not part of routine workup.

“There has to be a really good reason for me to order a calcitonin...I’m a less is more kind of person.” – Dr. Desai [33:43]

Special note: Molecular testing can sometimes detect medullary features overlooked by cytology.

---

Interpreting Ultrasound: TIRADS and Red Flags [34:01–38:16]

• TIRADS: Systematic risk stratification based on ultrasound features (like BI-RADS for breast).
  • TIRADS 1: normal; 2: benign; 3: probably benign; 4a/b: indeterminate; 5: suspicious.
• Suspicious features:
  • Irregular shape or margins
  • Calcifications/microcalcifications
  • Abnormal cervical lymph nodes (“cancer until proven otherwise” — Dr. Desai [35:53])
• Make sure your ultrasound order asks to “include cervical lymph nodes.”

Follow-up Intervals

• If benign nodule shows no significant change for >5 years, can usually stop ultrasound follow-up.
• Patient anxiety commonly drives over-testing — lengthen interval if possible. [38:16]

“If a nodule has not changed after five years, you can stop.” – Dr. Chindris [38:16]

---

Fine Needle Aspiration (FNA) and Bethesda System [41:58–47:50]

• Bethesda Classification:
  • I: Nondiagnostic
  • II: Benign (<2% malignancy)
  • III: Atypia of undetermined significance (AUS)
  • IV: Follicular neoplasm/oncocytic
  • V: Suspicious for malignancy
  • VI: Malignant
• Indeterminate results (III/IV):
  • Now often followed with molecular testing (reflexed from FNA sample)
  • Molecular results help risk-stratify further (e.g., certain mutations → higher risk)

“Molecular testing...does not tell us if it’s cancer...but if your molecular testing is positive, we have to take it out to see if it’s cancer or not.” – Dr. Desai [47:17]

---

Minimally Invasive Treatments for Benign Nodules [48:27–52:28]

• Alcohol Sclerosis: For large, fluid-filled (cystic) nodules—aspirate and inject alcohol to prevent recurrence
• Ablation (Laser/Radiofrequency): Outpatient, for benign solid nodules or shrinking functionally toxic ones; no anesthesia required
• For small biopsy-proven papillary thyroid cancers: experimental ablation techniques (radiofrequency) may be used in select cases.

---

Case 2: Thyroid Cancer Subtypes and Modern Management [52:28–69:29]

Case Scenario

• Woman with a palpable right thyroid mass → AUS on FNA → right lobectomy → pathology reveals papillary carcinoma → completion thyroidectomy.

Subtypes of Thyroid Cancer [53:23–62:20]

• Three Major Bins:
  1. Well-Differentiated (Follicular Origin)
     • Papillary (80%)
     • Follicular (10–15%)
     • Oncocytic (Hürthle cell; 2–3%; recently separated)
  2. Medullary (C cells; MEN2, RET mutations)
  3. Anaplastic (Undifferentiated, aggressive, universally stage IV)
• Papillary: “This is the one that has a five-year survival rate of like 99%.” [54:01]
• Anaplastic: “Everybody in that category is actually stage four on presentation, and a five-year life expectancy is pretty poor. It's like less than 10%.” – Dr. Desai [57:10]

Management Paradigm Shifts [54:01–62:20]

• Less aggressive: More hemithyroidectomies (hemi only), less radioactive iodine, less TSH suppression
• Total thyroidectomy plus radioactive iodine and suppression now reserved for higher-risk cases
• Pathologic risk stratification based on:
  • Lymph node involvement
  • Tumor size
  • Extra-thyroidal extension
  • Variant histology (e.g., tall cell variant)
  • Distant metastases
• Age under 55 = better outcomes, influences staging

---

Primary Care Follow-Up and Survivorship [64:08–70:43]

Follow-up after Cancer:

• For most well-differentiated thyroid cancers:
  • Annual TSH and thyroglobulin (if total thyroidectomy)
  • Periodic neck ultrasound (most closely spaced after diagnosis, intervals may be lengthened)
  • If patient has only hemithyroidectomy, thyroglobulin monitoring is not useful — will be detectable
  • If patients drop out of endocrinology care: seek to clarify cancer subtype, surgery, therapies received

TSH Goals:

• For hemi-thyroidectomy: most don’t need lifelong levothyroxine; TSH goal is normal range, not <2.0 as in old practice.

---

GLP-1 Agonists and Thyroid Cancer (Semaglutide, Tirzepatide, etc.) [70:49–78:42]

Key Question: Should you avoid GLP-1s for weight loss in someone with thyroid cancer history?

• Concern comes from early rodent studies of medullary thyroid cancer risk.
• Recent population studies (2023+) have not confirmed a significant risk for most thyroid cancer types.
• Major contraindication: Medullary thyroid cancer or MEN2 (multiple family members, RET mutation, pheochromocytoma).
• Papillary/Follicular (well-differentiated): GLP-1s considered safe and reasonable.
• Don’t routinely ultrasound the thyroid before starting GLP-1s unless there’s a nodule or concerning family/personal history.

  “If the answer is, ‘Yeah, I knew my family member got radioactive iodine, then there’s zero chance it was medullary.’” – Dr. Desai [73:32]

• Both endocrinologists use GLP-1 agonists in thyroid cancer survivors if not medullary/anaplastic.

---

Memorable Quotes

“Thyroid nodules are very common...The incidence increases with age, and the vast majority of them are benign. These are the three points that I tell them.” — Dr. Chindris [09:52]

“There is no good cancer. So for anybody who says that, don’t ever say that, everybody’s journey is a little bit different.” — Dr. Desai [53:41]

“Current paradigm in thyroid cancer is really considering what the long term side effects of treatment...less is more category.” — Dr. Desai [79:24]

“Ultrasound is the gold standard…in most cases it’s going to tell you what to do.” – Dr. Chindris [81:40]

---

Take-Home Pearls [78:58–81:40]

Dr. Ana Chindris (Thyroid Nodules):

• Most thyroid nodules are benign — reassure patients.
• Ultrasound is the gold standard for nodule evaluation.
• Be aware of molecular testing as an option after indeterminate cytology.

Dr. Kaniksha Desai (Thyroid Cancer):

• Cancer is never “good” — each journey is unique; acknowledge patients’ anxiety.
• “Less is more” in modern thyroid cancer care: more hemithyroidectomies, less radioiodine and suppression.
• For GLP-1 agonists: weigh overall benefits; avoid only in clear medullary thyroid cancer or MEN2.

---

Timestamps for Key Segments

• [08:55] Initial approach to incidental thyroid nodules
• [17:59] Local and systemic symptoms of nodules
• [23:25] Imaging: Ultrasound vs. radionuclide scan
• [28:55] Labs and role of calcitonin
• [34:01] TIRADS and ultrasound features
• [41:58] Fine needle aspiration & Bethesda categories
• [48:27] Ablation and minimally invasive procedures
• [53:23] Thyroid cancer subtypes and paradigm shifts
• [62:43] Risk stratification in well-differentiated thyroid cancer
• [64:08] Primary care follow-up and survivorship
• [70:49] GLP-1 agonists and thyroid cancer risk
• [78:58] Take-home points from both experts

---

Useful for Listeners:

• Confidently approach incidental thyroid nodules, know what to ask and how to examine.
• Understand when and why you may order imaging or further tests (and when not to).
• Clarify how to interpret and act on fine needle aspiration results.
• Recognize that most thyroid cancers, especially papillary, have excellent prognosis — and management can be conservative.
• Know when and how to use GLP-1 RA for obesity/diabetes after thyroid cancer, and what questions to ask about patient history.
• Reassure patients, minimize anxiety and overtreatment, and collaborate with specialists when needed.

---

End of summary.

Transcript

[A]

Hey, before we get to the show, I wanted to remind you to check out our [e-mail] curbsiders. If you haven't signed up yet, sign up now to get ad free episodes, twice monthly, bonus episodes, and a whole bunch of other cool [e-mail] curbsiders Paul, why couldn't the pony sing in the choir?

[B]

Probably because he was a little hoarse.

[A]

You got it. Is that the first time you've guessed?

[B]

Yep, that might be the first time I got one.

[A]

All right, Paul. Well, we might. Thyroid surgery might come up on this episode and, you know, hoarseness could be a problem there.

[B]

No, that's as close to relevant as you've been in quite some time. I'm really proud of you.

[A]

Actually, I haven't had in years.

[B]

The Curbsiders podcast is for entertainment, education and information purposes only. And the topics discussed should not be used solely to diagnose, treat, cure or prevent any diseases or conditions. The more the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity. Aside from possibly cash, like more hospital and affiliate outreach programs, if indeed there are any. In fact, there are none. Pretty much. We are responsible if you screw up. You should always do your own homework and let us know when we're wrong.

[A]

Welcome back to the curbsiders. I'm Dr. Matthew Frank Waddo, here with my great friend and America's primary care physician, maybe even the primary care physician, Dr. Paul Nelson Williams. Hi, Paul.

[B]

Hi, Matt. How are you?

[A]

Good. Well, we had two great guests tonight talking about thyroid nodules. Thyroid cancer. Our guests were Dr. Kaniksha Desai and Dr. Ana Chindras and they were wonderful guests. We were hooked up, Paul, by our good friends at the American association of Clinical Endocrinology. Who, Paul, We've been working with them for eight years now because we are old and I guess our show is getting old as well.

[B]

Yeah. No, I won't disagree.

[A]

Okay.

[C]

All right.

[A]

Well, Paul, before we tell them about our two wonderful guests, can you remind the audience what is it that we do on Curbsiders?

[B]

Sure, Matt. As a reminder, we are the internal medicine podcast. We use expert interviews to bring you clinical pearls and practice changing knowledge. And Matt, would you like me to talk about our two guests?

[A]

Sure.

[B]

Otherwise, what are we doing really? So we had a Great conversation with Dr. Kaniksha Desai and Dr. Ana Chendras. Dr. Kaniksha Desae is a board certified endocrinologist and clinical associate professor at Stanford University. She completed her endocrinology fellowship at the Mayo Clinic with an emphasis on the management of patients with thyroid cancer. Dr. Desai's clinical practice focuses on the management of patients with thyroid nodules and thyroid cancer. She also maintains board certification and neck ultrasonography. Dr. Ana Chindris has been a member of the Mayo Clinic Florida staff since 2014. She currently holds a joint appointment in the Department of Medicine Division of Endocrinology as well as Department of Cancer Biology. She is a treasurer of the Florida Endocrine association and her main areas of interest are thyroid neoplasia and she is the current recipient of the George Haub Family Career Development Award in Cancer Research. Matt on this episode we go through what to do about those pesky thyroid nodules that we pick up incidentally, maybe even the ones that we happen to find on examination. What is the next step in the workup? What happens if it would turn out that something that requires finial aspiration or even further management and sort of what kind of surveillance happens after someone might even have a diagnosis of thyroid cancer? And just to tease a little bit, I don't know if everyone else has been as panicked as I have about what to do with the GLP1 agonist and someone with a vague history of thyroid cancer, but we get an amazing framework as to who we should worry about and who we can worry less about. So a really pearl filled episode that I found extraordinarily helpful.

[A]

A reminder that this and most episodes will be available for CME for all health professionals through VCU Health at curbsiders.vcuhealth.org and if you haven't done so yet, sign up for our [e-mail] curbsiders where you can get ad free episodes, twice monthly, bonus episodes and a whole bunch of other stuff. Patreon.com curbsiders Ana and Kaniksha, thank you so much for joining us on the show. The audience has heard your bios but they need to know a little more about you. So Ana, start with you first. Can you tell the audience a hobby or interest that you have outside of medicine?

[D]

Yeah, I actually have many hobbies, but probably my oldest one is watching car racing formula, which I have been since med school and through all these years and more recently I got the opportunity to actually go to a few races. I'm trying to go to one every year. So went to the first race that ever was held in Miami a couple actually three years ago and the last two years we went To Montreal because after the Miami heat, we were. We got to go somewhere north. Can't take that anymore. So. So that would be that. And more recently, I started growing vanda orchids because Florida is a pretty good environment for that and you don't have to do much for them to bloom. So that's about it.

[B]

I have to ask. Yeah, well, it's. We. We've talked about before the gardening.

[A]

Our.

[B]

Our guests who garden just seem to be the most well adjusted people. I've killed a couple of tomato plants, so whatever that says about me. But I. The Formula one racing, you. Wait, so you started doing this in medical school. What were the circumstances? How did this happen? Was it just on TV or did you have a friend that was very much into it?

[D]

Yes, it was on tv. So I grew up in Eastern Europe under the communism. In 1990s, the Iron Curtain fell, so we had more access to shows, including to sports. My younger brother was very much into cars, and that's how I picked it up through him. And then he kind of fell out of interest that in terms of F1, but I stuck with it. And the very first race I actually attended was in Indianapolis in 2005. I was a resident in Michigan at that time, and so we wasn't that far from Detroit to go watch it. And it was. I actually got to see Schumacher, Michael Schumacher racing, you know, so he's a legend. I. I'm proud to have a couple pictures of him and.

[B]

Amazing.

[A]

Yeah.

[B]

I love this so much.

[A]

I know, I know. It's a Netflix. There's some reality show with the drivers now because my, My. My younger sister got into it and drive to survive.

[D]

Yeah.

[A]

Yep. They. So they watch that. Okay. And that's. That's cool. All right, well, Keniksha, we're going to ask you because we want to get to the topic, but we're going to ask you about advice or feedback that you've received that you found meaningful and that you can share with the audience.

[B]

Sure.

[C]

So a little bit about me. I trained on the east coast and then moved over to Stanford in 2016. And I think the best two pieces of advice that I have for trainees is that one, when you go around with attendings, just take the best of what everybody has to offer and then create your own style. So rather than copy just one person, a lot of people copy just their mentor. I think it's really great if you have many mentors and then you just take the good because everybody has some things they could do better. But if you could take this method to do really good and then create your own style. I think that's really great. The second piece of advice that I got that I found really useful is that, you know, keep an open mind about what's possible. Nothing is impossible. If you had asked me 15 years ago if I was going to be in California doing thyroid cancer and podcasting, I would have probably looked at you like you were crazy. So it's not what I had imagined. And I think a lot of people think medicine is a certain way. When they go through medical school, when they go through residency, they have this expectation about what medicine is. And I think it can be a lot more if you just keep an open mind.

[A]

Yeah, absolutely. I mean, Paul knew he was going to be a podcaster, but that's.

[B]

Yeah, that was always. I went to medical school specifically so I could get into podcasting. So it worked out pretty great.

[A]

Right? And cats, your cat will be here in any, any minute now. Did I just hear the cat, Paul?

[B]

No, that was not my cat, actually. I don't know what you heard.

[A]

All right. Paul's cat usually joins us for recordings. Basically the third co host at this point, Holly.

[D]

Had I known, I would have let my dog in here. I just closed the door on her.

[A]

Well, we're a cat show, Anna.

[D]

I'm sorry, but I have a cat dog. I have a shiba inu. So they do behave like cats. Very much like.

[A]

All right, all right, that's fair. Well, Paul, how about we get to a case from Cash, like, Because we have a lot to go through and I'm excited to get into it.

[C]

Sure.

[B]

So we're going to start with Mr. Ty Rad. Mr. Rad is a 68 year old male with a history of high blood pressure and tobacco use who recently underwent low dose CT for lung cancer screening. The results on the CT instantly note heterogeneity of the right lobe of the thyroid with multiple nodules. The patient is asymptomatic without any complaints at this time. You obtain a TSH which results at 0.86 and get a thyroid ultrasound which shows two right sided lower pole thyroid nodules. They're both described as solid or almost completely solid with sizes 3.8 by 2.3 by 2.2. So it sounds to me like a big boy. And then 1.8 by 1.3 by 1.1 cm respectively. So we have this patient. This comes up all the time. We were talking before we hit the record button with these low dose lung cancer screenings. We see These abnormal thyroid nodules all the time now. So from here, Ana, where would we go? So what else would we ask in terms of the history or what should we do in the physical examination as we start to think about how we're going to work up this patient?

[D]

First of all, I like your imagination with names, Mr. Thairad. This is pretty cool. He presents with an incidentally discovered thyroid nodule, or actually with a couple of them noted on unrelated imaging. There were a couple of things that came to mind when you were presenting the case and one you also pointed out at the end. Yes, we do nowadays see or get patients with thyroid nodules that are primarily diagnosed as incidental findings on unrelated imaging. So really, the clinical. Every now and then, we do see patients who were diagnosed through clinical exam, but this is by and large the majority as incidental lomas, if you want. The other thing I wanted to also emphasize is that the thyroid nodules are very common, and patients are usually reassured to hear that. This is pretty much the first line I tell them when they come with the complaint. So they are very common in the general population. The incidence increases with age, and the vast majority of them are benign. These are the three points that I tell them. But then really, when we assess a newly diagnosed thyroid nodule, we try to answer two questions, right? The first question, is it a benign or a malignant thyroid nodule? And the second question, does it cause any symptoms, is associated with any symptoms? So really, to answer your question specifically to this patient, I would ask Mr. Rad about his family history. Does he have any family history of thyroid cancer? I would ask him about personal history, any personal history of radiation exposure. And then I would ask him about any symptoms that could be attributed to these thyroid nodules, which, like you said, are fairly large. So any local symptoms. And in addition to that, because the tsh, although normal, is at the lower end of the normal range and his thyroid nodules are large, as we talked about, I would also possibly ask him about any subtle symptoms of hyperthyroidism, because sometimes you can see fluctuation in the tsh and you can see very low, you know, subclinical, if you want, or very low grade hyperthyroidism with the toxic nodule. So, so this is. This is basically how I was thinking I would start with Mr. Rad. So, yeah, for the physical exam, I would look, I would assess if the thyroid is mobile. So basically, so if it moves with swallowing, as you would be expecting, if there are any palpable masses in the neck otherwise, or if if there's any abnormal cervical lymphadenopathy. So this is, this is pretty much where I would start with this, with this guy.

[A]

Can I ask about the subtle thyroid symptoms, Paul? Is that what you're going to ask or something else?

[B]

I got other stuff, but yeah, I'd like to hear about those too. So. Okay, let's go.

[A]

You said maybe the subtle symptoms of hyperthyroidism. I'm only capable of diagnosing, not subtle. So can you tell us maybe we can get better?

[D]

Yeah, well, I had examples. I had a couple of patients in the clinic that really presented with. Honestly, it was pretty. Personality changes. Okay. They were, the, the family reported they were more irritable. They, you know, they were like snappier, if you want. They granted that the TSH in that particular person was lower, so, so it was clearly under the lower end of the normal range. But the T4 and T3 levels were, were still normal. So it was subclinical hyperthyroidism. But they did we, we did discuss about the low dose metamazole and, and with normalizing, her personality improved. And this was based on her family's reports as well. So that's occasionally what you see as a first, or at least in my experience, that's what I saw. Other patients can complain of palpitations. This is probably palpitations and heat intolerance are probably the next two or three, the two most common symptoms that are reported. But the reason I wanted to specify this is because we have, in this particular case, we have one TSH one point in time. But the TSH can also fluctuate spontaneously in toxic nodules. So if it's 0.8 now, it doesn't mean that it's not going to be 0.2 three months later, or it wasn't 0.2 four months ago.

[B]

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[C]

Foreign.

[B]

This episode is brought to you by Grammarly Folks, I'm not sure how it is for you, but for me being able to Main focus is one of the most important things in my workday and it's hard for me to do. If I'm putting together a presentation, I might be getting email messages and then I get a text message and then I get a patient care message and I have 37 browser tabs open and it's easy for me to start to lose focus and start to lose time in that way. So focus is really important for me. With Grammarly as your AI writing partner, you can stay focused and get through your work faster with relevant real time suggestions wherever you write. And you can download Grammarly for [e-mail] podcast. There's a lot of neat features of Grammarly and now starting to use AI to help improve your writing. And one of the things that I especially like is it allows you to choose your tone. So I was actually working on some of the copy actually for this specific ad read and just kind of playing around with Grammarly and it suggested I could choose a tone that was professional, persuasive and witty. You know, just just like I naturally am but enhanced and double checked by Grammarly and it works seamlessly like I could use it within Microsoft Word and you can use it throughout many apps and across multiple platforms. You can get more done without sacrificing the quality of the work that you do. Grammarly helps with any writing from brainstorming to sounding more confident and persuasive at work. 90% of professionals say that Grammarly has saved them time writing and editing their work. Four out of five professionals say Grammarly helps them gain, buy in and action through their communication. You can speed through the drafting editing process while staying on task. Write and edit quickly with context aware suggestions everywhere you write. Grammarly works across more than 500,000 apps and websites. 93% of professionals report that Grammarly helps them get more work done. Get more done with Grammarly Download Grammarly for [e-mail] podcast. That's Grammarly.com podcast. I also wanted to ask about symptoms just to be explicit because again I'M the dumb one on the show. But when you're talking about sort of the physical symptoms related to the nodules itself, are we talking, like, compressive symptoms, or are you asking about dysphagia or hoarseness? Is there anything else that you tend to assess when you're asking about those?

[D]

Thanks for asking more specifically. So the most common symptom that the patient reports in my personal experience in my clinic, is neck tightness. So they just feel like there's something that. That is pressing on their neck, and that's. And that's uncomfortable for them. If it's a large goiter, sometimes they can experience difficulty breathing when in reclined position. And as far as the dysphagia, yes, it's primarily with solids, and that's what makes. Helps you make the difference in terms of etiology, because solids and liquids, if they complain of both, it's most likely unrelated to the thyroid nodule. But I also have to say that the position of the nodule makes a huge difference, because I'm sure you also saw a lot of patients with large thyroid nodules that have absolutely no symptoms, and that's because they're laterally positioned. So size in itself is not going to be enough to. To be causing symptoms definitively.

[B]

And I promise I'll let you move on to the case. But anytime that I'm talking to endocrinologist about thyroids, I have to ask about the examination. As a reminder, learning in medical school, where we're from behind, like, we're stalking the patient and then theoretically having them drink from a soda straw, like, it's just all very improbable. So I would love to hear, actually, from both you and Kanishka, how you approach the thyroid examination. Are we from the front? Are we using thumbs? Is that okay now? So what is. What does your thyroid exam look like? I hope you don't mind me asking, Matt, but I'm asked every time.

[D]

No, it started through my training. It started like choking from behind. You know, that's basically how. That's how we were trained as well. And before COVID yes, we would give everybody the cup of water to swallow, and we would, you know, we would feel the thyroid moving with. With the swallowing. Unfortunately, with the COVID I kind of felt, you know, that we stopped doing that. So. So at this point, I have to say I just started doing it again just today, basically, for the first time after four years. And that's strictly because I wanted to show the patient, hey, this is your tyoe. So put your finger There, let's swallow, and then you're going to see what I'm talking about. But yes.

[B]

Oh, I bet they appreciate it. That's great.

[C]

Yeah. My only thing is that. So we can't feel things that are generally under a centimeter unless they're super, super superficial. So a lot of people get these small nodules that are found incidentally, and they're like, how come I can't feel it? But even with. If it's posterior, you might not actually even feel it up to, like, close to, like, 2 centimeters. And so, I mean, we. We do the exam from behind, as Anna mentioned, but I generally try to do one side at a time when I'm teaching my, like, residents and fellows. I'm like, don't press both. So use your fingertips and press one side and then prep the patients. You don't scare. You're doing this exam because most of all, you can do it from the front. So there's some endocrinologists that do it from the front, too. You can actually do it from the front. So there are many different styles.

[A]

Yeah. Someone told us they examine the thyroid from the front using their thumbs. Usually one side at a time, but. Yeah. Okay, good question, Paul. I like that. That was. I enjoyed that. Those answers.

[B]

I'm going to keep asking until I don't know what, but. All right, we can move on.

[D]

There actually are studies. There was one specific study that looked to see what's the threshold size wise, where, you know, and. And like Aniksha was saying, we miss 50% of thyroid nodules that are. That are over 1cm in size. People look behind, you know, under that.

[A]

This is good, Paul, because I've had a lot of patients, like, look at me with disappointment when they're like, why can't you feel my nodule?

[B]

You know, so you might be misreading why they're disappointed, Matt. I don't know.

[A]

I actually, before I listen to people's heart, I'm like, remind me, has anyone ever told you you have heart murmurs? Because I just don't want them to be disappointed if I don't comment on a heart murmur that they know they have anyway. So that's a little pearl for the audience if you want to avoid that mess.

[B]

Physical exam masterclass here. It's great.

[A]

Okay, so what we've talked about so far, we're asking about family history, radiation exposure, dysphagia for solids. Are they feeling tightness in their neck? That's not something that I would have thought to, so that I think That's a good tip. Are they having difficulty breathing? The subtle symptoms of hyperthyroidism could be personality changes, could be palpitations, could be heat intolerance. And you mentioned that the tsh, even if it was okay now it can fluctuate if they have like a high, like a functioning nodule. So we need to think for that. And all of us now, there's a lot of ways to examine the thyroid. Just tell the patient you're going to be grabbing their neck and, and let them know that if it's a small nodule, we might not feel it. All right, Paul, so where, where are we going to next with this imaging, maybe, or.

[B]

Yeah, so I guess where from here? I suppose. So we, you know, we, we happily this patient has come to us, you know, ready made with the TSH result, which we talked about a little bit, but sort of where. What is the next step? Will we proceed right to thyroid ultrasound based on the tsh? When would we decide to do a radionuclide thyroid scans or how do you think about imaging or the next steps of work for patients like this?

[D]

So, yeah, before, before doing that, can I go back to and maybe make one more observation about the risk factors? And that's pertinent to basically, yeah. History of thyroid cancer, that's one thing. But the history of radiation, because I actually had patients, it, yeah, it's extremely rare. But every now and then I do ask anybody, I do ask everybody if they have any history of radiation, but the radiation in childhood actually is more important than in adulthood. And I did have a couple of patients who actually grew up, and they were children in Ukraine at the time of Chernobyl accident. And one out of two actually did end up having papillary thyroid cancer. So that's important. It's important also that to note or to remember that whole body radiation in childhood and then also whole body radiation for bone marrow transplant, which can happen in both children and adults, has been associated with increased risk. So I just wanted to mention that now when it comes to the imaging, really, so ultrasound is the gold standard. And if you have a thyroid nodule that that's been just diagnosed and it did not have an ultrasound, I personally order an ultrasound in everybody. You know, I mean, the old algorithm was saying, oh, I'll check the dsh. If the TSH is suppressed, go to the move to the nuclear medicine scan. But I think in practice nowadays, we all would recommend obtaining an ultrasound because there's much more information that you get from that. So that would be the that would be next. In terms of the, in terms of the nuclear medicine scan, I have to say I do not order it as often as I used to when I started my, my endocrinology training and in the first years of practice. And I think, you know, I was, I was thinking about this recently. I think part of it is because in the past we used to treat more of these toxic nodules and multinodular goiters would radioactiv and I think the trend has changed over the past, you know, several years. In the past when you were treating with reductive iodine, you needed to have an uptake right percentage so you can calculate the dose. Most patients nowadays would prefer, if they are good candidates, would prefer to be on a, on a, on an antithyroidal medication met mezzo namely and patients with toxic nodules and multinodular goiters do need long term. So as soon as you try to back off the medication they will become hyperthyroid again. However they do need fairly low doses. So, so, so it, it appears more or appears less invasive and it's more appealing to them, you know, as opposed to going through the hypothyroidism, having to be on levothyroxine and so on and so forth. So I think that's made the main reason we don't do as much, we don't do the nuclear medicine scans as much. The other situation that we encounter because we are primarily a consultative practice, we see patients that are not local. Sometimes a two day test is not necessarily feasible for them. Unless we change my management, I don't necessarily order it anymore. For example, if I have as I mentioned, somebody with a multinodular equator bilateral nodules and controlled on a low dose methimazole, I wouldn't order it. But if you have a unilateral or if you suspect a unilateral toxic nodule in a patient who has local symptoms and you would consider the lobectomy, then in that case yes, it would make sense to do a scan and see confirm that that is the overactive nodule and how to plan if, if it's, if an intervention of this of this sort is considered. But, so that would be a scenario where I would, I would order the, I would order the nuclear medicines.

[A]

Yeah, you like Paul, that's something, a test that I always thought like I'd be ordering more of. And you're, and you're right, now that you mention it, I don't think I've ever ordered one. I don't know, Paul. Is that your experience?

[B]

Yeah, if you. Yeah, if I were paying attention to the boards, I'd be ordering them left and right. But you're right, it doesn't come from practicalities as much as I thought that it would like Theo's probably, which I thought I'd just be treating all the time, but it turns out not so much.

[D]

Yeah, I think it is primarily because the management has changed and pretty much the same with Graves disease. And I know this is not the main topic, but the vast majority of patients these days would choose the antithyroidals over radioactive iodine. So I can't tell you when was the last. I don't remember when is the last time I treated the Graves disease with radioactive iodine. Everybody would want to be an antithyroidal medicine and in the vast majority of cases, it is successful.

[A]

I do want to ask this patient we gave you has a TSH of 0.86. We didn't give a free T4. Are there any other labs you would get for this patient that we presented? Mr. Tyrad, rather. And then do people check calcitonin for this? That was something I was surprised to even hear about.

[D]

So, yeah, I like your question because that takes me to a couple cases that I had where probably. So to answer your question, in this particular person, probably not. I mean, just with the information that we have. So the TSH is low, normal, usually in order to. So TSH is far more sensitive than T4 and T3. So you would expect, in order for T4 and T3 to be abnormal, you would expect to see a TSH below normal. So with the TSH borderline or in the lower half of the normal range or closer to the lower end of the normal range, it is Most likely that T4 and T3 levels are going to be normal. Having said that, you can check the whole panel if you have any clinical suspicion that this could be an overactive thyroid nodule. But by and large, I think they will be normal. And I don't know, Kaniksha can, can agree or disagree with me, but in terms of the calcitonin. So let me tell you about my two cases. Okay. And then. And then I guess we can go from there. But I had two patients with thyroid nodules, so each of them had a thyroid nodule that ended up undergoing a fine needle aspiration. In their report, the cytology report came back Bethesda category four, as in follicular neoplasm with oncocytic features or possib the oncocytic neoplasm our institution has, basically it's FNA with reflux molecular testing. So we do save a sample at the time of the biopsy and if it comes, if the cytology comes Bethesda Category 3 or 4, we send it for molecular testing. This is what we did in both these cases. And much to our surprise, the molecular testing came back medullary thyroid cancer.

[C]

Cancer.

[D]

And that is because the oncocytes or former HERM cells and the medulla or C cells, where the medullary thyroid cancer originates from, can be very similar on cytology. And even experienced pathologists can actually be misled when they do the cytology and I mean, when they read the slides. And so if it wasn't for the molecular testing. Right, we probably wouldn't have found out about this unless we proceeded with surgery. Right? Because that's the way the old way used to. That's the old way we used to do things, right. If it was indeterminate or if it was in Bethesda 3 and 4, if you didn't have molecular testing available, then the D final diagnosis was based on surgery, right? So now with the molecular testing, we get these, this additional stratification. But if, let's say we didn't have reflex molecular testing and we had to bring the patient back to repeat the FNA in order to get a sample for molecular testing, an alternative approach would have been measuring the calcitonin. Knowing that the cytological diagnosis can be. I don't know that the pathologist can misinterpret the C cells for.

[A]

Oh, interesting. And audience, we are going to get to the Bethesda classification and we'll go through that. So that's a little tease of what we're going to talk about in a minute here. Kenexia, did you have anything to say about that part of it?

[C]

So, actually I did want to talk about that. In that when you're ordering something, I think it's really important two things to the pretest probability of whether something is really going to be useful and then costs. Like it's not cheap to order a calcitonin level and it's not cheap to order a free T4 level. So if it's going to change your management, definitely order it. But if it. If you're kind of borderline, I would say there has to be a really good reason for me to order a calcitonin. Like if there's a family history of thyroid cancer and multiple family members, I might consider it. Or you know, if they've had a feel, I'm like, okay, so this might be me. N2, one of the genetic syndromes. I might order it. But generally we don't order calcitonin level unless you're like, very special. Like if you get the molecular testing and then there's a RET positive, which I'm sure that's probably what the gene that came back was, then there's a good reason to order it. But otherwise I would kind of shy away from. I'm a less is more kind of person.

[A]

Okay, I like that.

[D]

Yeah. You do want to know. You do want to know what to do with the result. If you. If you order a test, that's.

[C]

And don't forget, patients get a copy of the results. So you have to be pretty confident that it's actionable if it's abnormal, because no one likes an unactionable abnormal thing that you just keep testing.

[A]

Such a good point on my tube, Stone. Such a good point on your tombstone, Paul. Well, okay, so let's briefly talk about the Tirads. Right. The American College of Radiology, I think it's. Yeah, the American College of Radiology has this Tirads, kind of like birads for breast cancer related to the thyroid ultrasound.

[B]

As far as much as I understand it. Please correct me if I'm wrong. So tirads 1 is stone cold normal, 2 is benign, 3 is probably benign, 4a is low suspicion, 4b is high suspicion, and 5 is bad business, probably malignant. Is that a fair summary to say? Could I ask you. And we'll have the reports, and those will be helpful to the specific question. But going back to our patient, so we have someone who's got, to me what sounds like a pretty big nodule that is described as either solid or almost completely solid. I guess my question for you are, what are the characteristics on a report other than the tie res criteria that should raise our eyebrows or make us nervous that we're dealing with something scary? Are there certain characteristics or features that we should read as particularly worrisome? I recognize that we'll have probably a categorization or recommendation from the read as well.

[D]

Well, I mean, the tie res do include those characteristics, by and large, because you're looking at the shape of the nodule. You're looking at whether the margins are regular or not. You're looking at whether there are some calcifications or micro calcifications. So all those features that we would normally look in a thyroid nodule are basically included in the thyroids. So I think, by and large, most of the nodules that we see, whether they are imaged in house or come from elsewhere, are classified based on the thyroid or an equivalent. But that is. So all those ultrasound features, all those morphological characteristics are included in the thyroids.

[C]

I think when you're looking at it. Also, one really bad feature is actually if there's abnormal lymph nodes, this is outside of module, but this is like cancer until proven otherwise. So if your radiologist is like, all these abnormal lymph nodes exist, yes, there's a chance that they might be reactive, but definitely biopsy those. I know we talked about. Endocrinologists would love to see all of your patients and biopsy the nodules.

[B]

But.

[C]

But our wait times are kind of long sometimes. So if the patient's having a lot of anxiety about waiting a couple months to see us, obviously waiting a couple months for like 99% of patients is not going to change the outcome. I really want to empower primary care doctors to really go ahead and biopsy that while you're waiting. Schedule the visit, biopsy it. And then we have something else to talk about when we see the patient, too. Like, we can go over the biopsy results as well. Like, so if the patient's really, I want something sooner than later, go ahead and do it. We do our own biopsies. Anna and I do our own biopsies, and we would love to do the biopsies, but we obviously can't see even all the endocrinological stuff. They couldn't just see all the right nodules that exist because it's so common.

[D]

And on that note, I also wanted to mention. Kaniksha brought up a good point with respect to the cervical lymph nodes, but I want to make an observation on that. So not all the ultrasound studies that I personally see coming from other facilities include the lymph nodes. So some of them are strictly limited to the thyroid. And sometimes it just has to do with the way the order is written. So, for example, when you issue an order for thyroid ultrasound, you may want to say, please include cervical lymph nodes. And in that case, they will specifically add that. Add that imaging in. But it really. The protocols vary a whole lot from institution to institution. So sometimes you just need. All it needs to be done is to specify that in the order in order to get the whole, you know, the complete imaging.

[A]

And before we get to the next part of the case, the other thing I just wanted to ask, and because this comes up all the time too. Like if someone's had ultrasounds, maybe they've had a biopsy that was benign and they like, at what point can we just stop ultrasounding them or stop worrying about this thing?

[D]

Yeah. So I'm hoping that the, you know, American Thyroid association is supposed to come out with guidelines and they were supposed to come out this year, but it's most likely gonna be 2025. So at this point we don't have definitive guidelines. I think through the Thai rads, through the American association of Radiology, there, there are some guidelines in a sense that if a nodule has not changed after five years, you can stop. But I have to say, if it was benign and it didn't change subsequently, you don't have to follow up beyond five years. But I have a problem convincing the patients of that, especially if they are younger.

[A]

It sounds like you're in the same boat as Paul and I where the person's just, if they want the ultrasound, they're just getting multiple. They've had 10 thyroid ultrasound and, you know, it just, they're like, okay, you're, it's still the same as it was.

[D]

What I tend to do, I do lengthen the follow up interval and I do tell them, you know, I do tell them, okay, if it's the same next time, then the following time is going to be three years or five years. And then eventually I do say, you know, at this point we get to where this can be followed on a clinical basis and only if you experience any local symptoms or you don't need another ultrasound unless you experience any local symptoms.

[B]

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[C]

Like.

[D]

Yeah. So you have category one, which is non diagnostic. So essentially the pathologist was not able to give you a result based on the sample that they had to analyze. The Bethesda category two is benign. So those are the benign thyroid nodules. Final aspirations are very high accuracy. So it's extremely unlikely that a nodule that's categorized Bethesda 2 is going to turn out to be malignant at the end. It's about 2% risk for malignancy excluding NFP. Bethesda 3 is ATPI of unknown significance. Bethesda 4 is follicular neoplasm or follicular neoplasma oncocytic type. And then five is suspicious for malignancy and six is malignant. I believe your your question was about Bethesda category two. Right. So the benign thyroid nodule. So if this is so if we get that type of result on a patient. I usually tell them that I recommend an ultrasound in one to two years. I know that some say six to 12 months, but Patel's. Again, it is a little bit on a case by case basis. But if we do the biopsy, we're comfortable with the needle placement, we're comfortable with the pathology reading. It's less likely, it's quite unlikely that this would not be accurate. Than most patients are fine with aerobic ultrasounding. Lunch, two years.

[A]

Okay, so basically you just to recap, so one is non diagnostic. So we're kind of stuck there. Two is benign. And then you said three is this undetermined. Atypia, Atypia of unknown significance. Unknown significance. Four is follicular, five is suspicious for malignancy, and six is malignant. And basically the category three and four from my reading are the kind of the, the indeterminate ones where.

[D]

Right.

[A]

And that was the case you were giving the example of before where you said it reflexes to. Like a molecular test.

[D]

Yeah. So before the molecular testing was developed. So like when I was a fellow, for example, or a little bit before then. So the way I'm explaining this to the patients is the following.

[A]

Oh, this is great.

[D]

So I drew that. I'm drawing the thyroid and then I drew a circle, which is the nodule. And I tell them that the difference between benign and malignant in the 3 and 4 categories is given by the status of the nodule, the capsule of the nodule. So if the capsule is basically invaded or penetrated with cells, then that makes it cancer. If the capsule is intact, then that means it's a benign adenoma. When we poke the nodule with the needle, we don't get any information on the status of the capsule. And the pathologist in these particular categories cannot tell benign versus malignant based on the way the cells look like. That's my, that's what I tell them. And so before we had the molecular testing and before the molecular testing was, you know, the performance of the molecular testing testing improved to, you know, to. Today, the only modality to get a definitive diagnosis was to do a lobectomy, do frozen sections. The pathologist would section the capsule, look under the microscope and see how the capsule looked like. Now we have the molecular testing. So we don't need to do this. We don't need to do the surgery beforehand. The molecular testing. There are a few, few options out there, but in a nutshell, it's looking for mutations or for genetic abnormalities that are typically seen in a cancerous nodule, and they're not seen in a benign one. And that's basically how you get an additional result in terms of what's the potential risk of malignancy in a nodule. And this can go anywhere from under 3% to greater than 70%, so depending on which test you're looking at. But that's kind of how I. How I describe it.

[A]

Wow. So that's like a major change that. Because I don't remember learning about the molecular testing at all until I was reading this. Because, like, I'm sending people endocrinology and largely I'm not knowing what's happening, like, on the back end of things too much. I don't know about you, Paul, but that's how I feel. So I think we should move on to the next case.

[C]

I make one comment about the molecular testing. The molecular testing does not tell us if it's cancer. I just want to clarify. It downgrades the risk of it being cancer if it's not cancer. So those are the nodules that we can follow. But if your molecular testing is positive, we have to take it out to see if it's cancer or not. And there's a good chance it still might not be cancer. Like, what I was saying is that it can range, like, sometimes it's a 50% risk, sometimes it's a 75% risk. It can provide a risk, but it cannot tell you definitively that it's cancer.

[A]

Yeah. So we'll definitely have the endocrinologist involved if we're messing with molecular testing and everything. But that's good to know that it's available now and it's helping to risk stratify people. Before we move on to talking about cancer. Kinexia in your section, I did see that for some nodules. Sometimes there are some newer treatments, like injectable things you can do or burny things you can do to nodules. So, Ana, did you want to talk a little bit about that? And maybe kinectia can fill in any other gaps?

[D]

So, yeah, this is a great point. And indeed, we don't talk about it too often because it's fairly new in the United States, although it has been minimally invasive treatments for thyroid nodules have been practiced in Europe. Italy is at the forefront there. But it really. These are modalities that would avoid surgical interventions for benign symptomatic thyroid nodules in primarily. So there are a couple. There are basically two categories. If you're talking about treating a large symptomatic thyroid cyst so completely fluid filled. Then this is something that we have been doing as well. And that's alcohol sclerosis of that particular cyst. So you basically aspirate the cyst and then re inject pure alcohol along with a little bit of the cyst fluid. The idea is to create a scar inside the walls, the assist walls, and prevent that fluid from cystic fluid from reaccumulating. And that's because when you aspirate large persists, they very often just come back. That's what it is. So by injecting alcohol, you try to prevent that from happening. For solid nodules, there are two treatment options. There's laser ablation and radiofrequency ablation. The approach basically differs with the institution, but the idea is the same. Basically you apply laser or you apply a current within a large nodule with the intent to shrink that. So, so you create a scar. It gets initially larger as a result of inflammation, but then it gets smaller over, over the next following months. There are some pros and cons for each of them. You know, it's practiced by surgeons, interventional radiologists and some endocrinologists. So different types of specialties can actually do this. And again, the biggest advantages that the people people get, get to keep their thyroids right. One prerequisite is to have two benign biopsies prior to this. So you want to make sure that what you're treating is truly a benign nodule because once you applied that particular procedure, current or laser, the architecture of those cells changes and it's very difficult to make an interpretation of a biopsy afterwards. One more thing I wanted to mention, if it came to, since we're talking about this, some institutions actually do radio frequency ablation for small biopsy, proven papillary thyroid cancer. So this is an upcoming method and we don't have long term follow up on that. But so far the recent data suggests that you can successfully destroy very small, typically less than 1cm, papillary cancers confined to the thyroid. So there are some criteria to select those candidates, but that again is something that's newly, I mean, has been happening recently.

[C]

Yeah. So I do want to make a plug that endocrinologists do this procedure. It's an outpatient procedure. That's the great thing about it is that there's no anesthesia. It's a completely outpatient procedure. The recovery time is a little bit longer than. Well, it's a short recovery time overall. But if you're shrinking a nodule, obviously, obviously taking it out, it makes it Go away the shrinking immediately. Right. So there's the length in that aspect, but it is pretty well tolerated. It's completely outpatient. And then the only other thing that I was going to add is that you can use it for taxicadinomas as well. And you can radiate the nodule so that the patients actually use thyroid afterwards. And so you don't have to worry about hypothyroidism with radioactive iodide or with surgery when you've removed the noise nodules.

[B]

All right, let's move on to our next case. So we'll talk about Ms. Theoglobulin. We'll make her even Theodora, just for consistency sake. She's a 62 year old female. She has history of COPD and hyperlipidemia. She presented initially due to a painless right anterior neck swelling of uncertain duration. On exam, she had a palpable enlargement of the right lobe of her thyroid. And we even thought that her trachea was slightly displaced to the left. An ultrasound showed two solid nodules on the right side, the first being 3.7 cm and the second being 3.4 in the maximal dimension. Fine needle aspiration was performed, and this demonstrated atypia of undetermined significance, which is Bethesda Category 3 on shared decision making between the patient and the surgeon. The patient decided to undergo right lobectomy with its mastectomy, which I said as fast as I could because I knew I was going to mispronounce it. Surgical pathology was consistent with a papillary carcinoma confined to the thyroid gland. And the patient was subsequently brought back to the OR two months later for a complete thyroidectomy.

[D]

So.

[B]

So before we dig into sort of how we manage her from here and sort of the specific details of the case, could you just give us the broad overview of the subcategories of thyroid cancer and how they're different? I feel like we all learn these at some point, and it's so easy for me, at least, to kind of forget about the nuanced differences. So can you talk us through them, please?

[D]

Sure.

[C]

Okay, so I just wanted to start with when people think of thyroid cancer, there's this idea out there that it's a good cancer. I just want to debunk that there is no good cancer. So for anybody who says that, don't ever say that everybody's journey is a little bit different. Thyroid cancer does, in general, have a very excellent prognosis, but they're very different types. When we're thinking about Thyroid cancer, I think of it as in three buckets. The first bucket is well differentiated thyroid cancer. The second bucket is the C cell medullary one. And the third bucket is anaplastic. The way that we differentiate those is based on the type of cell. For differentiated, it's going to be follicular for the medullary sisy cell and then we're going to see does it look like a thyroid cell, so is it differentiated or is it more like it's mutated into some other thing that's unrecognizable? And that's what puts it in the anaplastic category. For the differentiated one, Traditionally, most people just learned about two papillary and follicular. There's actually a third type that got reclassified by the WHO recently. In 2022, there was a subtype of follicular known as Herthel CE cell, and that got reclassified as its own third category under differentiated, now under oncocinic. So each of those three things, even though they're in the broader group of well differentiated, they do have slightly different pathophysiology and they have slightly different outcomes because of that. So the papillary is what people think of as the good cancer that a lot of people think of. That's the one that has a five year survival rate of like 99%. That 1 is actually spread through the lymph nodes. The majority of patients, it is confined to the thyroid gland on presentation, but about 20, 30% of people, it can actually go to the lymph nodes at the time of presentation. That's why we get our ultrasound to make sure that it hasn't spread. We want a really good ultrasound of those lymph nodes to make sure it hasn't spread because it changes our management. As I said earlier, I'm a less is more girl. Actually, the ATA has swung the pendulum a little bit on how much treatment these patients need. So thyroid cancer patients, traditionally everybody got a total thyroidectomy, everybody got radioactive iodine, and everybody got lots of thyroid hormone. So those days left, those days are gone. About 15 years ago, we stopped doing that. So now we have a hemithyroidctomy as a main treatment option, which we just take out half the thyroid gland. And we do radioactive iodine only in higher, intermediate to higher risk patients. And we don't do as much levothin suppression therapy. And I think that's going to be kind of important as we talk about the treatment for this patient later. So for the papillary we have A option of surgery as the primary treatment and then followed by if it's higher risk, we're due radioactivity. And that's very similar to how follicular works as well. But the difference is that follicular tends to to metastasize more through the bloodstream. And so you can get these distant meths to the bones. And so it has a slightly worse prognosis than papillary does, but they kind of get grouped together in the way that they're researched currently. But it does have a slightly worse prognosis than papillary. And papillary is about 80% of differentiated and follicular ends up being about 10 to 15%. And then oncocytic is rarer. It's about 2 to 3% of well differentiated thyroid cancers. And it, depending on the mutation, which Anna has done research in this, it can be really worse prognosis or some of the mutation will actually make it a little bit more towards a prognosis of like papillary and follicular thyroid cancer. So not everybody who has oncocytic is it's going to be bad in. But if it is, if you have certain mutations like tert mutation, it could be considerably workers. Okay, so those are the well differentiated. So those three. Then there's this category medullary. So everybody's probably heard of medullary because it's on your boards. It's associated with me. 2. So this is that genetic condition where you can have a pheochromocytoma with the thyroid cancer and this is caused by a majority of them are caused by RET mutations that tend to run in families. If it tends to be in a germline mutation and the treatment for this is actually surgery. And depending on the mutation, it might even be surgery and testing in your children. When you get the genetic testing, there's a genetic counselor that recommends what kind of screening is associated with your family and what kind of treatment moves forward based on the specific gene in the RET mutation that you have. There is no radioactive iodine treatment for medullary because it works on C cells and not the follicular cells. The radioactive iodine doesn't work in this group of patients. Comparatively to the differentiated one, we use normal tsh. There's no levodioxin suppression. Then the last group, which is the really, really bad thyroid cancer, it's actually bad cancer in general, comparatively to most cancers, is probably one that has the worst prognosis out there, which is anaplastic thyroid cancer. It's the most aggressive type. It's the one that we all get scared about because the patient wakes up with a huge, huge expanding neck mass overnight and they can literally choke to death within like a week or two if you. Depending on where we catch it in the cycle. Like it's, it's not great. So everybody in that category is actually stage four on presentation, and a five year life expectancy is pretty poor. It's like less than 10%. So we have been making strides on improving the outcomes in these patients based on recent testing. If they have a BRAF mutation, there's some new adjuvant chemotherapy that we can use to kind of shrink the tumor prior to resection. But we have a long way to go in that category. And the treatment for that is actually surgery if you catch it early enough that you can actually surgically resect it and then external beam radiation. So we don't use radioactive iodine and anaplastic, and we don't use TSH suppression in anaplastic because those two also don't work in anaplastic. So those are kind of the main overview of thyroid cancer. I would say when you're staging thyroid cancer, it comes in the classic four stages of other cancers. But interestingly for the well differentiated one, it's actually staged based on age. For the PTC, FTC and the oncocytic. If you're under the age of 55, you can only have a stage one or stage two. And stage one is anywhere in the the neck. And stage two is like distant metastatic disease. And the reason for that is even if you have distant metastatic disease, if you're young, your prognosis like these are treatable things and your 5 year and 10 year survival is still pretty good. It's not what's traditionally associated with the stage four, like breast cancer or colon cancer. So they try to restage it based on that. And then the same thing with anaplastic, because it's so terrible, everybody is a stage four in presentation. So there's a little bit differencing in stage three for thyroid cancer than is for other cancers. The other thing that we look at is that the ATA has these kind of risk stratification. So we're looking at if you're under 55 and you have a lot of neck disease, for your papillary thyroid cancer, your prognosis might still be okay as far as mortality and morbidity, but what is the risk of the cancer recurring after the primary treatment that we choose to do? So we put it in three buckets. In this low risk, which is the cancer coming back is usually less than 5%, somewhere between 1 and 2%. Intermediate risk, which can be anywhere from 10 to 30%, and high risk, which is usually associated over 40 to 50% risk that cancer is coming back. That really helps us define what we want to do for our primary treatment. So the more the risk of the cancer coming back, the more treatment we're going to do in the beginning. So if it's high risk, we're going to do a total thyroidectomy. If it's high risk, we're going to do radioactive iodine and if it's high risk, we're going to do extra thyroid hormone for suppression, at least in the beginning, as opposed to if it's low risk, we're going to back off on doing all of those things because of the risk of complications from all of the treatment options that we have. So I know that's a lot of information to take in.

[A]

The risk that you were just talking about is that mainly for the well differentiated types like the medullary thyroid, the anaplastic, those are probably automatically.

[C]

Those are separate.

[A]

Separate. Okay, so for well differentiated, how are you determining what's like low risk, intermediate or high risk is it is based on the size and the lymph nodes and what factors in there combination of.

[C]

All of those things. So it's based on the final pathology. So, so it's size is one thing. Generally if you have a larger cancer, it can be more intermediate risk. Size alone isn't going to make it high risk though. There are variants of papillary thyroid cancer that make it a little bit more high risk of recurrence. So these are things that you might see on the endocrinologist notes, this tall cell variant or hobno variant or columnar variant. So it's not classic PTC in the PAP report. So those things tend to keep coming up back because they're not how traditional papillary thyroid cancer goes. And then the more lymph nodes that you have, the higher risk of it recurring is because the less chance that we have of like kind of getting it all out in the beginning when we do the treatment. That is one of the reasons why we use the radioactive iodine is to like the. Those are kind of the patients that have the most data on preventing morbidity and mortality from thyroid cancer is those high, higher risk patients. But if you have a lot of lymph nodes and they're really big lymph nodes and that Makes you high risk. And then anybody who has distant metastatic disease to the lungs or the bones, automatically they're going to be high risk. And those are. The radioactive iodine works really well in the lungs, not so much in the bones. But some patients do still get good treatment with radioactive iodine to the bones too. It's we, we get scans and we see where the treatment.

[A]

Paul, what do you want to know about this? As America's primary care physician.

[B]

I guess I would like to know what they think that I should know. So I think oftentimes we see patients with a history of thyroid cancer and I'm always. And they've sort of lost touch with their endocrinologists and I'm not quite sure what our TSH goal should be or how aggressive. Should I do surveillance ultrasounds? Where do I go from here? And what is sort of typical follow up if someone has not seen endocrinology for a while for someone who's had a history of cancer or, or is it totally dependent on the type of cancer that they had?

[C]

So partly it depends the type of cancer that they had.

[B]

Oh, that's not what I was hoping to hear, but okay, carry on.

[C]

Most of the patients actually are low risk and excellent prognosis. So the higher risk ones generally will tell you that. My endocrinologist says I have to keep seeing them forever. So there's a little bit of onus on the patient as well. Right. So they tell you a little bit of history about their cancer. And I try to educate, educate my patients on, you know, this is the type of thyroid cancer you had, the papillaries of follicular, what kind of treatments. They should know if they've had like total thyroidectomy or radioactive iodine. And ideally they would be at least in the beginning, followed for at least a short period of time to see what kind of response to treatment they've had. Right. So assuming that they're low risk and they've had an excellent response to treatment, current recommendations are to get an annual thyroglobulin level. So that's once a year. Once a year we're getting a TSH to make sure their dose of thyroid hormone hasn't, doesn't need to be adjusted as they age or as they gain or lose weight or as they change medications. These are all reasons to adjust it. And then periodic neck ultrasound. So it's kind of a, the guidelines are kind of vague on, like, is this going to be one year, is this going to be two years, Is this going to be five years. We are working on newer guidelines to kind of differentiate that. And when can we stop monitoring? That's a good question as well. For our GUR guidelines, we don't stop monitoring, but I think the newer ones are going to give a little bit more definitive, like, here's when we can stop monitoring. After five years, if they've had excellent response to treatment, you can probably skip the ultrasounds at some point. So what I do in my own practice is that initially in the first couple of years, I get more frequent ultrasounds, usually a 6 to 12 month months. And then as time goes on, I kind of space them out. Of course, it depends on the patient's anxiety level, how comfortable they are with just that, thyroglobulin screening. Is the thyroglobulin able to be a good screening marker for that patient? And those kind of factors come into play whether I get more ultrasounds or less ultrasounds. And actually with COVID a lot of people, we, believe it or not, we've had to postpone our ultrasound because they, you know, couldn't come in or they have a cold and now they're not allowed to get an ultrasound anymore. You know, people went years without getting ultrasounds and they actually, they actually did fine. The main thing is that you're getting the TSH regularly for the dose of the thyroid hormone and that you're getting the thyroid globulin ideally once, like a year, just to do it as a.

[A]

Screening, connect with people. Some people getting hemi thyroidectomies. Now, are many of those patients still needing replacement therapy?

[C]

BE yeah. So this is a good question. So when we started with the hemi hemithyroidectomies, we had an ideal TSH goal of 0.5 to 2.0. So we were trying to make them in the bottom half of normal. But what we found out is that if you take out, traditionally if you take out one lobe, about 80% of people actually don't need any sort of thyroid hormone replacement. So it's like having one kidney versus two kidneys. Yes, you are at slightly higher risk of getting ckd, but that doesn't mean you're going to get at it. So most people actually didn't. And then when we put this TSH goal of.05 to 2.0, now we're actually on the opposite. Like 60 to 80% actually required thyroid hormone. So the I goal of doing the hem. One of the goals of doing the hemithyroidctomy is that you didn't have to take Lifelong thyroid hormone replacement. But when we, when we started doing less is more, we didn't have a lot of data to say, is this actually okay? Okay. But now that we've been doing it for a decade, we have a lot more data, and we're going to actually change that recommendation on one of the upcoming guidelines and say that, hey, if you're. You should just keep the TSH goal normal rather than trying to make it.05 to 2.0. So if they're normal and they're not hypothyroid. No, you don't have to start thyroid hormone replacement. That's what I do in my practice. I have a conversation with the patient. Some people feel very symptomatic if their TSH is like 3. And those are the people that you're going to get thyroid hormone replacement to. Whether or not works, placebo effect, I don't know. But those are the people that you're going to give the thyroid hormone replacement to anyway. But if I have a bunch of patients who are totally adamant that I don't want to take extra hormone, and this is why I did hemithyroidectomy, and I can't remember to take the medication, and I'm like, okay, if your TSH is like 2.5, 3.2, you're actually probably statistically going to be fine. We didn't have the data for a long time, but now we have more data and we're like, okay, actually, they are fine. So we don't necessarily need to do that extra step. So there'll be more coming out on that. But not everybody who gets a hemithyroidectomy will need thyroid hormone.

[A]

And of course, if we do relax the TSH goal, we'll be checking the annual tsh, the thyroglobulin, the periodic neck ultrasound. So hopefully, if things start to go awry, we. We would pick up on that.

[C]

Yeah. If the patient wants to be seen by an endocrinologist, just send them back anytime.

[D]

Except for if you have a lobectomy. So a patient treated with a hemithyroidectomy, the thyroglobulin is not really useful in that case because it's going to be detectable because of the remaining lobe. So at the beginning, we used to measure that. At least in our practice, we kind of gave up on. So at the beginning, we wanted to see if. If we can make anything out of the result. But it really. Additional data came out and it's not really useful. So. So really that we don't typically measure that in patients treated with just hemi, thyroidectomies.

[C]

But the hemipyroidctomy ideally would be chosen because they're very low risk.

[D]

Right, Right.

[C]

So if you chose properly for a patient to get a high methyurertic, then you wouldn't necessarily need all of this monitor monitoring as well.

[A]

Okay, Paul, any other questions about monitoring? I know we're towards the end and I want to talk about GLP1s, but any other questions?

[B]

I think we've hit my high points.

[A]

Okay.

[B]

Yeah. And I do want to save time for the GLP1 question because it's going to come up more and more frequently.

[A]

Go ahead, ask away. I'll let you do the honors. Yeah.

[B]

So the question is, what do we do with this? So I feel like with the GLP1s, there was this theoretical concern for increased risks of thyroid cancer. Cancer when you're screening for family history and personal history and. Yes. Have you ever had, when you're dealing with men, type 2 syndrome, and the patients look at you like you had two heads because no one's actually ever heard what that is. So I guess what does the data show us right now? How concerned should we be? Should we be screening all patients that we start on these agents? What is the current thinking among our endocrinologic experts about the risk of thyroid cancer, specifically with the GLP1 agonist now that everyone is on them?

[C]

Yeah. So I think a lot has changed in the last 20 years about how we feel about this. So GLP1 agonists have been around for almost years. 20, 20 years. So they were initially treated just for plain diabetes and then nobody cared other than if you had medullary. Yep. But it was an endocrinologist who would usually be more bothered than primary care. Right. Whether you're going to start this medication or not for diabetes? Because it was like kind of clear cut. And then we started using semiglutide, which is a higher dose of the medication that can cause weight, that promotes weight loss, as opposed to just diabetes management. And then all this data started coming out about whether there's this increased theoretical risk of thyroid cancer. And in 2023, there was a French study that came out that was looking back on it, that they did a retrospective review of diabetics and they didn't really account for a lot of control factors, but they did find a slightly higher risk of thyroid cancer. Since then, we've had multiple other studies that have come out that say, no, it's not as high as we initially thought. But I Think the main thing is that we also have to weigh the risks and benefits of the obesity treatment, because obesity itself causes diabetes, it causes hypertension, it causes arthritis, it causes a lot of comorbid conditions. So I think there's a lot of factors that go into it. I don't think we have, like, years. We don't have decades of data as far as using it for weight loss medications, because the dose is a little bit more for the weight loss medications. That being said, statistically speaking, they probably had papillary thyroid cancer. Well differentiated thyroid cancer. Because if they. If they had a remote history. It's very rare to have a remote history of anaplastic. So you can take that scratch out of it. Medullary. Most people have multiple family members with medullary, and most people will know that they have medullary. I feel like we really hone that into the patients. If they have medullary. Yeah. So if they have a remote one family member that may have had thyroid cancer, you could ask, you know, did you get a hemi thyroid? Well, if it's very remote, you could actually ask if they got radioactive iodine. So if the answer is, yeah, I knew my. My family member got radioactive iodine, then there's zero chance it was medulla. So that quickly takes it off the table. If they are on extra suppressive thyroid hormone also should take it off the table, because endocrinologists don't give excess thyroid hormone for medullary thyroid cancer. If the patient's having severe anxiety about their family history, then, yeah, don't use it. But I don't think that otherwise it would have. Just having one person with a remote family history of thyroid cancer would have necessarily stopped me from using a GLPing1 agonist in a patient.

[A]

Paul, that's just such a smart way that we can now try to narrow down, like, what type of thyroid cancer was in the family. That's that you gave us a lot of clues there. It's really good.

[C]

Yeah. And with medullary, multiple family members have it too. So I'd be more suspicious than if it was like one aunt somewhere here, as opposed to my mom, dad, brother and sister all had thyroid cancer. But I didn't know exactly what it was right then you'd be a little more. Okay, that's too many people to be having thyroid cancer for it to not be some sort of familial gene mutation. So I think just diving a little bit more into the history sometimes helps with that. And honestly, there are some people out there who are actually still even looking at GLP1 use in medullary. So you will see some case reports and some studies coming out about that in the next couple of years as well. So I know it's contraindicated currently, and I personally don't use it in my medullary patients, but there might be some data coming out on that as well in the future.

[D]

I think you also have to keep in mind that medullary is quite rare compared to the differentiated, compared to papillary, it's about 3%, you know, of all thyroid cancers. So the likelihood of coming across these, it's, it's, it's quite small. And then the other thing that, the other question that we get in practice, for example, is like, should we get an ultrasound? Should we look for thyroid nodules in anybody who intends to go on a GLP1? And at this point, at least to my knowledge, there's no such recommendation in terms of screening.

[C]

Yes. But I, I personally do not screen unless I have a very good reason to screen. Because you will find, like over the age of 50, 50% of people have their pills and you're going to be on the rabbit hole of, oh, my God, Now I have this other problem that I found in my patient. Now I have to biopsy it, now I have to do this, now I have to do that. And then like two years later, you're down the line and finally start the GLP one. Right. So I would say, you know, I don't get ultrasounds in these patients. Our guidelines don't recommend getting ultrasounds currently. Something might change in the future, but currently there's no recommendations for getting ultrasounds in these patients. Now, if you do a neck exam and you feel a lump, then yes, sure, get an ultrasound.

[D]

Right.

[C]

But assuming that your physical exam is normal. No, I get it.

[B]

You know, it's funny, Matt, because I, I don't feel like I've been doing this a long time. Like, in my heart, I still identify as an early career physician, but I remember the days of fighting the fight to get daily exenatide for a patient and feeling like I was a cutting edge genius. And now that that is a medication that seems just quaint and bygone and from a different era. So, yeah, I've forgotten how long the GLP1 agonists have been around, but at least as long since I was in training.

[D]

Yeah, I was in training too, when that was, I think, the only one. And liraglutide came on towards the end of. Yep.

[A]

So, Keniksha is it fair to say if a patient had a hemithyroidectomy for papillary thyroid cancer and they weighed 300 pounds and they wanted to take semaglutide or tirzepatide for weight loss, and we've gotten them through their cancer, it would be reasonable to use it. They don't have medullary thyroid cancer or anaplastic, then it would be okay to use.

[C]

Yeah, I use it in my cancer. I treat a lot of thyroid cancer and we use it regularly in our thyroid cancer.

[A]

Okay, that's good to know because it will come up. I'm sure it will come up for people in the audience.

[C]

Yeah, those are two different pathophysiologies. If you had cancer and is it going to cause a recurrence versus if you never had cancer, is it going to cause cancer in the first place? I think we have more data on that. If you never had cancer, is it going to cause cancer? Which I don't think it's a super increased risk. I don't think it's statistically significant enough for me to currently change practice. I think there's even less data on the recurrence. But we do use it in a lot of of our thyroid cancer patients because as you may know, thyroidectomy patients for some reason tend to gain weight more than the normal population. So we do use it frequently in our patients as well.

[A]

Okay. All right. Well, this has been a lot of fun and I learned so much from this talk. Thank you to both of you. So, Ana, we'll start with you. If you could give the audience one or two take home points you want them to remember about thyroid nodules.

[D]

Most of them are benign. So I think the, I think the take point, take home point, number one, is that you can probably reassure the patients in the vast majority of cases. Number two, take home point would be. I have to think a little bit. I'm sorry.

[A]

Okay. Well, we can go to Kaniksha if you want to give us some take home points on thyroid cancer cancer.

[C]

Sure. I covered this before. There's no good cancer. So every patient's journey is different and I think it's important to meet them where they are in the journey. There'll be some patients with more anxiety than others. And it's really important to acknowledge that. For the patient's sake and for your sake, please acknowledge that and don't brush them off again. Cancer is not a great thing to have. That's my first tip. My second tip is that the current paradigm and Thyroid cancer is really considering what the long term side effects of treatment, such as total thyroidectomy, radioactive iodine, TSH suppression. What are these risks? Years out from treatment. And so we've actually had a shift in how we manage these patients in the less is more category. So we do more hemithyroidectomies, we do less radioactive iodine treatment and we do less TSH suppression. And then the third tip that I had is that the DLP agonists use. So I think you really need to consider the bigger picture regarding obesity and comorbid conditions. Do they have diabetes, hypertension, arthritis, Will the weight loss get them off these medications and generally improve their quality and quantity of life? So I think those are kind of important things to consider.

[A]

Okay, fantastic. Ana, unless you thought of anything else, I think we can end there. You gave us so much already.

[D]

Well, I think from everything that we discussed, this would be. So that would be the main thing, that they are common and the vast majority of them are benign. So we can reassure the patients of the, of that. The second point would be that the ultrasound is the gold standard. So it's, in most cases it's going to tell you what to do with that particular thyroid nodule, whether you can stop there and just monitor versus proceed with further intervention. And then I don't know. I think the third point would be related to the molecular testing. So really being aware that that is an option that will reduce the number of surgical interventions. So it can be used or it should be used and the primary care physicians can order it as well, in addition to the biopsy.

[A]

All right. And I wanted to just remind everybody that we have to thank the American association of Clinical Endocrinology for hooking us up with two great guests for this episode. Check out their website, their guidelines, they do great work there. And with that, we will go to our outro.

[B]

This has been another episode of the Curbsiders bringing you a little knowledge food for your brain hole.

[A]

Yummy.

[B]

If you're still hungry for more, join our Patreon and get all of our episodes ad free, plus twice monthly bonus episodes at patreon.com curbsiders you can you can find our [e-mail] and while you're there, sign up for a mailing list to get our weekly Shownotes in your inbox. This includes our Curbsiders Digest which recaps the latest practice, changing articles, guidelines and news in internal medicine.

[A]

And we're committed to high value practice, changing knowledge and to do that. We want your feedback, so email [e-mail] it also helps when you subscribe, rate and review the show on YouTube, Spotify, Apple Podcasts. A reminder that this and most episodes will be available for CME credit for all health professionals through VCU healtherbsiders.vcuhealth.org A special thanks to our writer and producer for this episode, Dr. Elise Burke, and to our whole Curbsiders team. Our technical production is done by Podpaste. Elizabeth Proto does our social media. Jen Watto runs our Patreon Chris the Chumanch who moderates our Discord. Stuart Brigham composed our theme music and with that, until next time, I've been Dr. Matthew Frank Waddo and as always.

[B]

Remain Dr. Paul Nelson Williams. Thank you and goodbye.