QD Clinic: GLP-1s and History of Thyroid Cancer? Save
Daric Mueller, PA-C, St. Clair Shores, MI, presents this case as part of RheumNow's "The Obesity Imperative" campaign, presented in September 2026.
Transcription
Welcome to Obesity QD Clinic. I'm Derek Mueller, PA from St. Clair Shores, Michigan. And today's case is titled "Of Mice and Men." A 37-year-old female with a history of obesity, depression, and papillary thyroid cancer status post total thyroidectomy with a BMI of 35. She was referred to our clinic about 3 years ago for possible inflammatory arthritis on the basis of recurrent plantar fasciitis and marginal elevations of ESR and CRP.
When we first examined this patient a few years back, she had no obvious subjective signs of inflammatory arthritis, dactylitis, enthesitis, no axial disease, HLA-B27 negative, no personal or family history of plaque psoriasis, IBD, or uveitis, and essentially she's been managed symptomatically with celecoxib. However, over the years, any attempt to withdraw or reduce the therapy results in quite significant worsening of her plantar fasciitis. Her orthopedist has managed her with local injections. Unfortunately, the response is fleeting and plantar fascia corticosteroid injections aren't the most pleasant. So she really asks at her most recent visit, short of surgery, is there anything else that can be done?
So this opened the floor for a conversation about things we can do to manage her weight, which may have a mechanical impact on her plantar fasciitis. So I pose the question, has anyone to date ever talked to you about GLP-1 agonist drugs? She says, I can't take those. And I say, why? What do you mean? And she said because of her history of thyroid cancer.
So is this indeed a hard stop in the history of treated thyroid cancer? Every GLP-1 agonist therapy in the United States — semaglutide, liraglutide, tirzepatide — they all carry a box warning for thyroid tumors. We'll come back to that. So the clinical question: if your patient has a history of thyroid cancer, can you still prescribe, or can someone still be prescribed, a GLP-1 agonist? And really the whole answer to this question hinges upon what type of thyroid cancer. So we're going to get into that here next.
So first of all, what is even the association with thyroid malignancy and GLP-1 agonists? So this really seems to be a story of rodents — rats and mice. Rats and mice, their thyroid gland cells or parafollicular cells are chock-full of GLP-1 receptors. And just going back to some basic physiology, these are the calcitonin-secreting cells around the gland. So it does seem that in rodents, GLP-1 agonist therapy binds to the C cells or parafollicular cells of these rodent thyroid glands, and that seems to enhance the risk of medullary carcinoma in rodents, and that does seem to be duration and dose dependent in those animals. And this is really purely a receptor-mediated phenomenon. GLP-1 receptor knockout mice do not get medullary carcinoma when exposed to GLP-1 agonists. And this also happens without interference of the RET proto-oncogene that drives human medullary cancer or multiple endocrine neoplasia.
So it's a rodent story. Humans and monkeys have very little GLP-1 receptors on their C cells in their thyroid glands. Even monkeys exposed to GLP-1 agonist therapy at 60 times the human exposure for over 20 months did not, in a study, show any C cell hyperplasia or medullary carcinoma. So it's species specific, it seems to be an issue at super-therapeutic dose signals, and there's really no human or primate relevance that we know of.
So what are the actual restrictions that are on the US label? An FDA contraindication to any commercially available GLP-1 agonist therapy only contraindicates therapy in two groups, and that's people who have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. Medullary cancer is driven by C cell pathology. Theoretically, we're extrapolating that warning from rodents. And that's really the whole list.
So what's not on the list is the most common types of thyroid malignancies that you may encounter in your patients. So that's papillary thyroid cancer and follicular or differentiated thyroid cancers. These are different cell lineages, totally different biology. We're not really seeing that as a risk. So there's no convincing evidence that outside of medullary thyroid cancers the risk does exist.
Some pharmacovigilance data has suggested a very faint signal for non-MTC perhaps within the first year of GLP-1 agonist prescription, but my thought is it might be a selection bias — you know, if you're prescribing GLP-1s to patients and you're asking about thyroid history, and you hear about a nodule or a vague family history, that's when people are going to get scans, they're going to get tests.
and you might pick up on those non-MTC cancers. Okay. So really the big key takeaways of this, and also some extra nuggets, the actual contraindication for GLP-1 agonist therapy is quite narrow. That's people with a confirmed or family history of medullary thyroid cancer or MEN — multiple endocrine neoplasia. Uh, so always ask about personal or family history, and if need be, getting records from endocrine or surgery about a patient's thyroid malignancy history.
Um, so papillary and follicular thyroid cancer is not a contraindication. Um, also there's no recommendation for routine screening with thyroid ultrasounds or calcitonin screening. Uh, that's not anywhere in the label, that's not indicated. And then also something to be aware of in patients who have a history of papillary thyroid cancer or cancer where essentially they've undergone total thyroidectomy — those patients are going to be on some dose of thyroid supplementation or levothyroxine. Uh, and if a patient is starting GLP-1 therapy, that's going to delay gastric emptying, which can shift the absorption of a patient's thyroid replacement therapy. So really important to just be aware of that, that it may be relevant that the patient may need some adjustment of their levothyroxine dose, or the logistics of their dosing, if you were to prescribe a GLP-1 agonist to a patient such as that.
Um, so in this instance, we went through — in our patient we went through the data, we went through the fact that there was not a legitimate contraindication based on her history of papillary thyroid cancer. So, um, a GLP-1 agonist was offered, but she still deferred to double-check with her endocrinologist. So, I await our next meeting to flush this out further, and hopefully we can help her out with her pain that may very well be driven by biomechanics and obesity.
Uh, so that's it. Thanks for listening, and keep in touch with RheumNow and all this exciting content on RheumNow's Obesity Month. Thank you.
When we first examined this patient a few years back, she had no obvious subjective signs of inflammatory arthritis, dactylitis, enthesitis, no axial disease, HLA-B27 negative, no personal or family history of plaque psoriasis, IBD, or uveitis, and essentially she's been managed symptomatically with celecoxib. However, over the years, any attempt to withdraw or reduce the therapy results in quite significant worsening of her plantar fasciitis. Her orthopedist has managed her with local injections. Unfortunately, the response is fleeting and plantar fascia corticosteroid injections aren't the most pleasant. So she really asks at her most recent visit, short of surgery, is there anything else that can be done?
So this opened the floor for a conversation about things we can do to manage her weight, which may have a mechanical impact on her plantar fasciitis. So I pose the question, has anyone to date ever talked to you about GLP-1 agonist drugs? She says, I can't take those. And I say, why? What do you mean? And she said because of her history of thyroid cancer.
So is this indeed a hard stop in the history of treated thyroid cancer? Every GLP-1 agonist therapy in the United States — semaglutide, liraglutide, tirzepatide — they all carry a box warning for thyroid tumors. We'll come back to that. So the clinical question: if your patient has a history of thyroid cancer, can you still prescribe, or can someone still be prescribed, a GLP-1 agonist? And really the whole answer to this question hinges upon what type of thyroid cancer. So we're going to get into that here next.
So first of all, what is even the association with thyroid malignancy and GLP-1 agonists? So this really seems to be a story of rodents — rats and mice. Rats and mice, their thyroid gland cells or parafollicular cells are chock-full of GLP-1 receptors. And just going back to some basic physiology, these are the calcitonin-secreting cells around the gland. So it does seem that in rodents, GLP-1 agonist therapy binds to the C cells or parafollicular cells of these rodent thyroid glands, and that seems to enhance the risk of medullary carcinoma in rodents, and that does seem to be duration and dose dependent in those animals. And this is really purely a receptor-mediated phenomenon. GLP-1 receptor knockout mice do not get medullary carcinoma when exposed to GLP-1 agonists. And this also happens without interference of the RET proto-oncogene that drives human medullary cancer or multiple endocrine neoplasia.
So it's a rodent story. Humans and monkeys have very little GLP-1 receptors on their C cells in their thyroid glands. Even monkeys exposed to GLP-1 agonist therapy at 60 times the human exposure for over 20 months did not, in a study, show any C cell hyperplasia or medullary carcinoma. So it's species specific, it seems to be an issue at super-therapeutic dose signals, and there's really no human or primate relevance that we know of.
So what are the actual restrictions that are on the US label? An FDA contraindication to any commercially available GLP-1 agonist therapy only contraindicates therapy in two groups, and that's people who have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. Medullary cancer is driven by C cell pathology. Theoretically, we're extrapolating that warning from rodents. And that's really the whole list.
So what's not on the list is the most common types of thyroid malignancies that you may encounter in your patients. So that's papillary thyroid cancer and follicular or differentiated thyroid cancers. These are different cell lineages, totally different biology. We're not really seeing that as a risk. So there's no convincing evidence that outside of medullary thyroid cancers the risk does exist.
Some pharmacovigilance data has suggested a very faint signal for non-MTC perhaps within the first year of GLP-1 agonist prescription, but my thought is it might be a selection bias — you know, if you're prescribing GLP-1s to patients and you're asking about thyroid history, and you hear about a nodule or a vague family history, that's when people are going to get scans, they're going to get tests.
and you might pick up on those non-MTC cancers. Okay. So really the big key takeaways of this, and also some extra nuggets, the actual contraindication for GLP-1 agonist therapy is quite narrow. That's people with a confirmed or family history of medullary thyroid cancer or MEN — multiple endocrine neoplasia. Uh, so always ask about personal or family history, and if need be, getting records from endocrine or surgery about a patient's thyroid malignancy history.
Um, so papillary and follicular thyroid cancer is not a contraindication. Um, also there's no recommendation for routine screening with thyroid ultrasounds or calcitonin screening. Uh, that's not anywhere in the label, that's not indicated. And then also something to be aware of in patients who have a history of papillary thyroid cancer or cancer where essentially they've undergone total thyroidectomy — those patients are going to be on some dose of thyroid supplementation or levothyroxine. Uh, and if a patient is starting GLP-1 therapy, that's going to delay gastric emptying, which can shift the absorption of a patient's thyroid replacement therapy. So really important to just be aware of that, that it may be relevant that the patient may need some adjustment of their levothyroxine dose, or the logistics of their dosing, if you were to prescribe a GLP-1 agonist to a patient such as that.
Um, so in this instance, we went through — in our patient we went through the data, we went through the fact that there was not a legitimate contraindication based on her history of papillary thyroid cancer. So, um, a GLP-1 agonist was offered, but she still deferred to double-check with her endocrinologist. So, I await our next meeting to flush this out further, and hopefully we can help her out with her pain that may very well be driven by biomechanics and obesity.
Uh, so that's it. Thanks for listening, and keep in touch with RheumNow and all this exciting content on RheumNow's Obesity Month. Thank you.
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