Neurologic Complications of Endocrine Disorders With Dr. Rafid Mustafa

Neurologic complications of endocrine disorders are diverse and may arise before systemic manifestations. Early recognition is essential because neurologic symptoms may represent the presentation of an undiagnosed underlying endocrine disorder, and because many neurologic complications of endocrine disorders are reversible with timely treatment.

In this episode, Gordon Smith, MD, FAAN, speaks with Rafid Mustafa, MD, author of the article “Neurologic Complications of Endocrine Disorders” in the Continuum® February 2026 Neurology of Systemic Disease issue.

Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia.

Dr. Mustafa is an assistant professor of neurology for the Department of Neurology at Mayo Clinic in Rochester, Minnesota.

Additional Resources

Read the article: Neurologic Complications of Endocrine Disorders

Subscribe to Continuum®: shop.lww.com/Continuum

Earn CME (available only to AAN members): continpub.com/AudioCME

Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Host: @gordonsmithMD

Guest: @RafidMustafa

Full episode transcript available here

Dr Smith: So what group of disorders causes cognitive changes, weakness, fatigue, neuropathy, and seizures? Kind of sounds like all of neurology in one, doesn't it? It turns out that disorders of the endocrine system can cause all of these neurological problems and others. And kind of reminds me of William Osler, who famously said at the end of the 19th century that “he or she who knows syphilis knows medicine.” Syphilis was the great imitator of his time. I wonder if in our time, the great imitator is actually endocrine disorders because it can cause all of these different problems. Today I have the great opportunity to talk with Dr Rafid Mustafa from Mayo Clinic about the neurological complications of endocrine disorders, which is a really terrific article in the February 2026 issue of Continuum.

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.

Dr Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Rafid Mustafa about his article on neurological complications of endocrine disorders, which appears in the February 2026 Continuum issue on neurology of systemic disease. Rafid, welcome to the podcast, and please introduce yourself to our listeners.

Dr Mustafa: Well, thank you for having me, Dr Smith. Like you had mentioned, I'm Dr Rafid Mustafa. I'm a neurohospitalist at the Mayo Clinic and I had the pleasure of writing this issue with Dr Aaron Berkowitz, and it's been such a fun ride to be a part of Continuum for this issue.

Dr Smith: Yeah, it's a really exciting issue. And I have to say, I was really excited to have the opportunity to talk to you. Even though my research is in diabetes and I'm looking forward to talking about that---not my research, but about diabetes---I think the area of endocrine and neurological complications of endocrine disorders is confusing to us. And I guess maybe you could begin by just this concept that most of us check a few endocrine labs on just about everything. But how do you bring order to this when there's a group of disorders that all cause just about every domain of neurological problem, be it weakness, neuropathy, cognitive changes, and so forth?

Dr Mustafa: Yeah, I think it's super interesting. I think that's why, you know, this issue on systemic diseases is fun. I had a mentor one time telling me that your interim year in residency is important so you can learn about all these organ systems that are there to keep the brain alive. And so, I think neurologic complications of systemic disease are fun. You know, like you said, the endocrine system, whenever it goes awry, you can get all sorts of neurologic complications. Putting order to it can be challenging. I think it's important to know what the different parts of the endocrine system do, the different glands and how they're connected, and what to look out for when you encounter neurologic problems, because sometimes those neurologic manifestations can be the very earliest sign of something wrong with different parts of the endocrine system.

Dr Smith: You knew exactly where I was heading without having to tip my cards. I mean, that's exactly where I wanted to begin, because I think of this as an intimidating topic, but in reading your article, you outlined kind of the glandular structure or anatomy of the endocrine system and sort of the logic of its function. And actually, it's not as complicated as I was thinking going in. You did a good job of framing. And I wonder if maybe you can begin by just reminding our listeners the basic anatomy and functional logic that they'll need to keep in mind.

Dr Mustafa: Yeah, absolutely. The system itself is this network of different glands and hormones that work to influence each other, just like our, you know, our nervous system is all interconnected as well, too. But this is more ensuring homeostasis in various ways. So, you have the hypothalamus all the way at top that secretes things, usually just to stimulate the pituitary, which often ends up being the controller of the endocrine system. And then there are these various other organs that have different jobs or things to do. So, there's, you know, the thyroid, parathyroid, adrenal glands; you have your pancreas, there's gonads. And all of these different things have different roles to keep us healthy and regulated. to function appropriately, you know, whether that's just generalized metabolic things from the thyroid gland or more flight or fight responses from the adrenal gland, even, you know, renin, aldosterone, etc, etc, from the adrenal. And then you know, the pancreas, diabetes, all sorts of things there. Gonads are important for sexual health. It's kind of cool how it's all regulated together and there's these feedback loops and- ah, we'll have fun talking about it.

Dr Smith: Just listening to you, it kind of feels almost like the endocrine system is part of the nervous system, isn't it? I mean- and there are these sort of relationships between the two that I know we'll get into. We think of insulin sensitivity, for instance, and, you know, patients with diabetes. I mean, there's neuronal insulin resistance as well. So, they're very, very interconnected systems.

Dr Mustafa: Absolutely. You're absolutely right.

Dr Smith: I wonder if you can talk about this idea of feedback loops. This is something that we all learned in medical school, but probably worth reminding ourselves of as we begin the conversation.

Dr Mustafa: Yeah, one part of the endocrine system is important for secreting a hormone that will influence another part of the endocrine system. And that new end target will have some kind of function, and then it all loops together. So, for example, the hypothalamus, it secrets out thyrotropin-releasing hormone and that stimulates the anterior pituitary gland to secrete thyroid-stimulating hormone, and then that hormone acts on the thyroid gland itself to produce the final-acting thyroid hormones themselves, like T3 and T4. Now, if any of these are thrown off, then it throws off other parts of the system. So, for example, maybe you’re hyperthyroid and you have too much T3 and T4 coming from the thyroid gland. That may signal the hypothalamus and pituitary to reduce levels of thyrotropin-releasing hormone and thyroid-stimulating hormone to in turn affect the thyroid gland and help reduce production of those end-target thyroid hormone. Or vice versa, it just depends on the condition. You can see this at all aspects of the system at various accesses. So, it's kind of this complicated neural network in a way, but just from endocrine purposes, glands and hormones.

Dr Smith: I wonder if we can start talking about the pituitary gland. Your article has all kinds of really cool information. One pearl that I wasn't really aware of is that 10% of adults have a pituitary microadenoma. It's pretty amazing. You point out that most of these aren't clinically significant, but they clearly come up on, kind of, an evaluation now and again. I mean, how should our listeners sort through how to approach these situations, right? Most of them aren't clinically significant, but some of them are. What does a neurologist need to know about this?

Dr Mustafa: Yeah, To me, it's like anything else in our field. You scan enough people, you're going to find incidental things. You scan a spine, you're probably going to find a disc herniation. The question is, how clinically relevant is that and how is that affecting your patient? What are the things you need to be worried about and how do you work through it? As you mentioned, yeah, 10% of the population has a pituitary microadenoma. Those are the small ones. Most of them are clinically insignificant. So, if you find it, you know, usually it's not something to worry about too much. You might repeat serial imaging just to make sure it's not growing. But if they're not having neurologic symptoms because of mass effect or physiologic symptoms because of hormonal effect, then most of the time it's just an incidental finding and you just have to work really hard to reassure your patient. Now sometimes, there can be mass effect as the tumor itself grows, as benign tumor, or there can be hormonal effects. And then you might start thinking about how you're going to intervene.

Dr Smith: Let's talk about macroadenomas and mass effect. You spend some time, and I actually have a really good example of pituitary apoplexy as well as the relationship between macroadenomas and other headache syndromes. So maybe you can talk about the relationship between macroadenomas and headache?

Dr Mustafa: Yeah. So, you know, when pituitary adenomas become large, usually over 10 millimeters or so, we call it a macroadenoma. And the neurologic symptoms that come to play are usually because of mass effect. I think many of us are trained to recognize visual defects like a, you know, bitemporal hemianopia from compression of the optic chiasm. That's one of the classic things. But even just the mass effect alone in that area can cause symptoms like headache. Many of this will be, you know, migrainous in nature. Sometimes you can get a typical trigeminal-type phenomenon, just given everything that's in the region. And with something like pituitary apoplexy that you alluded to, I mean, that usually comes on very quickly. It can be a thunderclap headache. So, not all thunderclap headaches are subarachnoid hemorrhage from aneurysms. You have to think about other things on the differential, and that includes pituitary apoplexy.

Dr Smith: Yeah, I mean, I think one of the things I found interesting was the fact that headaches can be associated with pituitary macronoma that are migranous or even look like a trigeminal autonomic cephalgia. I mean, is that something that commonly influences your management of either the headache or the macroadenoma? I mean, if you have a patient with a macroadenoma, do you treat the headache syndrome any differently, or are you particularly attentive for pituitary findings in someone that you're scanning because of headache?

Dr Mustafa: Yeah. From my perspective, if I know there's a pituitary macroadenoma and they have these associated headaches, my practice is in general to treat the headache symptomatically, focusing on the phenotype, whether it's migrainous or more, you know, like an attack, a trigeminal autonomic cephalalgia. Now if it starts with they had an atypical headache like a trigeminal autonomic cephalgia, maybe I'm doing the imaging as a result of that to explore why they may be having this from a structural perspective. And if indeed it is because of a pituitary macroadenoma, we'll probably be monitoring the characteristics of the adenoma on a serial basis to see how it transforms over time. And if it's enlarging, you know, those symptoms might be a reason to consider intervention from a surgical resection standpoint.

Dr Smith: So, I wonder if we should pivot and talk a little bit about how neurologists encounter patients who have symptoms related to endocrine disorders. And presumably the clues come with the impact of the distal endocrine gland, for instance, either over- or underproduction of the thyroid hormone. Is that the right way of thinking of it? And then, you know, having identified that, you'll start to look whether it's a primary glandular problem or upstream in the pituitary.

Dr Mustafa: Absolutely. That's in general my approach. You know, often these patients are coming to the neurologist with specific symptomatology, and being familiar with how that's related to the endocrine system is what's important. So, I try to organize this article kind of by parts of the endocrine system and how that's related to neurologic manifestations. But really, it's about being familiar. So, if the patient presents in a comatose status and it's not a clear-cut structural reason, neurologically, as to why they're comatose, you might be exploring metabolic reasons for their coma. You may find disturbances in thyroid hormone levels, and that can influence you to work your way back up the axis---just like you mentioned, Gordon---to see where the problem is coming from that influences the thyroid problem.

Dr Smith: So, you know, maybe we can use that as a good hook to hang our coat on, right? So we have a patient in the unit, comatose, not clear why. Are there specific pearls or indicators that would trigger you to really think about, is this a thyroid problem? Is it adrenal or whatnot? I mean, you give some great examples of, like, myxedema coma, which is very interesting. But what's the clue that we should be going down this pathway? Or, you know, on the other extreme, do you just look for thyroid abnormalities in everyone with a coma that you're having a hard time figuring out?

Dr Mustafa: Great question. I am slightly more of a traditionalist in my approach to neurologic disease that, instead of shotgunning every single possible test, I try to localize in any way I can. And what's cool about these disorders of the endocrine system is that there's so much on your examination that can help clue you in. And it's not just the neurologic exam, it's the systemic exam as well, too. So, important to keep an eye out for those things. Since we're on the topic of thyroid, patients with mixed edema coma, you know, they may have neurologic signs like myoedema, etc, but they may also have systemic signs like hair loss, changes in weight, changes in temperature regulation, that you can pick up on history as well, too. And it's putting all that together to localize to not just part of the nervous system now, but part of the body that helps you with your testing. And that's how I tend to approach things.

Dr Smith: So, so many questions I have for you. I wonder, can we talk a little bit about Hashimoto's encephalopathy?

Dr Mustafa: Oh, yes, absolutely.

Dr Smith: What's the deal there? That's something I've always found a little bit challenging. So, when should we think about it? There are lots of people out there with elevated thyroperoxase antibodies. How do you make the connection between serology and clinical phenotype and management?

Dr Mustafa: Yeah, it's a great point of contention among groups, this diagnosis of Hashimoto encephalopathy. There are those that believe in this is a distinct autoimmune, essentially encephalitis entity associated with abnormal thyroid antibodies. And then there are those that believe that patients have this encephalopathy, but it's just incidental that we find these abnormalities in thyroid testing. What I'll tell you is there's been some really nice studies looking at Hashimoto's or what's to be Hashimoto's encephalopathy, and most patients that present with what is thought to be that actually have normal thyroid function studies. The other thing is finding abnormal antithyroid antibodies is also pretty prevalent in the general population. So, I think in my approach to thinking about Hashimoto's encephalopathy, you’ve just got to take everything with a grain of salt. You got to recognize that some things are just very prevalent, and you have to keep your clinical suspicion high for what you normally would see and consider other things on the differential. My personal thought is that there probably is some unique antibody-driven disease process that represents what we think of as Hashimoto's encephalopathy, but we just haven't fully classified what that antibody may be quite yet. And then there's probably some overlap, because in general a lot of these thyroid diseases themselves are reflective of underlying autoimmunity. So, there's probably something going on, but I don't think it's a direct effect of something like, you know, thyroid peroxidase antibodies.

Dr Smith: Maybe we should pivot and spend a little time talking about the most common endocrine disorder that we encounter in neurologic practice, which is diabetes. And as I mentioned earlier, it's a topic near and dear to my heart. What's the latest that our listeners should know about regarding peripheral nervous system complications of diabetes? We're all familiar with distal symmetric polyneuropathy. Or are there other new updates or pearls that we should be thinking about?

Dr Mustafa: Absolutely. So, the complications on the nervous system extend far beyond just your distal symmetric polyneuropathy is probably the most common thing we see, but you can get all sorts of unique manifestations. In fact, I recently just took care of a patient that had many of these. You can get a single thoracic radiculopathy. You can have what we see often at Mayo Clinic here, a diabetic lamosacral radicule plexus neuropathy where patients have profound, initially, usually pain in their lower limbs, and then this spreading of profound weakness in their lower limbs. That can be a huge complication of association with rapid control of glycemic status. And especially this day and age where we have newer medications that are very effective at controlling diabetes, we're seeing this more and more. I wrote this article before some recent publications that come out highlighting the association with GLP-1 agonists. But with these types of medication, rapid glycemic control can result in, you know, associated DLRPN quite frequently.

Dr Smith: Yeah, it's interesting. I think we think of the, kind of the neuro-ophthalmological manifestations or risks of GLP-1 agonists, but the relationship too, of treatment-induced neuropathy and diabetes. And I'm curious of your experience. My sense is that if you aren't attuned to these sort of problems, you often miss them. And you certainly see people that come close to having surgical interventions or, you know, end up going off in the wrong direction with these acute neuropathies that I think are probably a little more common than we often give them credit for.

Dr Mustafa: Absolutely. Yeah. I think, you know, learning about these things and being familiar is very important. It's important to keep a good broad differential because there can be mimickers, whether it's infectious things or malignant things like lymphoma, but I wanted to highlight in this article how common something like diabetic radiculoplexus, Lumbosacral radiculoplexus neuropathy can be. I mean, in fact, we see this more than things like Guillain-Barré syndrome, CIDP, etc. And so, I think practicing neurologists everywhere should at least be familiar and know what to look for so that they can make the diagnosis appropriately when they encounter patients with these debilitating diseases that can improve significantly.

Dr Smith: So, I have one other diabetes question. That's a central nervous system complication that I wasn't particularly familiar with, and I'd love to hear you talk about a little more. And that is the diabetic striatopathy. Am I saying that right?

Dr Mustafa: Absolutely. Yeah, yeah.

Dr Smith: Yeah. Talk to us about that. That's pretty cool.

Dr Mustafa: Yeah. You know, I think many of us that practice in the hospital setting will encounter patients with severe hyperglycemia. We're trained to recognize it as a stroke mimic. So many times these patients will come in, you know, glucose is in the six hundreds, thousands. And they might be just comatose, they might have focal neurologic signs that can mimic stroke. But one unique feature to be on the lookout for is diabetic striatopathy. And it's really thought to be an influence of out-of-range glycemic control on the basal ganglia itself. And so, these patients can present with unilateral hemibilismus, hemichorrhea, essentially a basal ganglia disorder. If you image them, you'll often see T1 hyperintensity in the striatum on MRI. And as you control the glycemic status, these patients improve. And it's just a unique phenomenon, but it's not- you know, many neurologists will see one of these probably in their careers. So, it's not something that's super rare that you'll never see it.

Dr Smith: I think we're probably about out of time, Rafid. I wonder if there's anything that I didn't ask you about that you really think our listeners would like to hear. What nugget did I miss? And there are a great many from which you have to pick, I'm sure.

Dr Mustafa: I think you've done such a great job. It's been a pleasure to chat with you. For me, the biggest takeaway for everyone to be aware of is oftentimes the first manifestation of something being off with the endocrine system will be something neurologic. And so, these patients may present to the neurologist first, or the neurologist will be consulted first, for something that seems purely neurologic. But it's important for us to have a high index of suspicion that the root cause could be something outside of the nervous system to help guide management down the line. When you're facing a patient with coma or peripheral neuropathy or myopathy or unique syndromes like the LRPN, remember to look beyond the nervous system, as this could be a very big clue to helping patients recover from disorders that are very, very treatable.

Dr Smith: Rafid, thank you so much. It's been a great conversation. Your article is truly outstanding. Topic is kind of complicated, but it's not as complicated as I thought it was going into it. And I certainly learned a lot and enjoyed it a great deal. So, thank you for spending time with me today. 

Dr Mustafa: Thank you so much for having me. I appreciate it.

Dr Smith: Again, today I've been interviewing Dr Rafid Mustafa from the Mayo Clinic about his article on neurologic complications of endocrine disorders, which appears in the February 2026 Continuum issue on neurology of systemic disease. Be sure to check out Continuum Audio episodes from this and other issues of Continuum, and thanks for joining us today.

Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.