Welcome to our webinar on clinical pearls from JCEM Case Reports. My name is Bill Young. I'm the editor-in-chief of JCEM Case Reports. Our co-host for this webinar is Dr. Adina Turcu, who is our deputy editor of the journal. In this webinar, we will be highlighting three cases that have been published in the journal this year. For each case, we'll have a presenter and a content expert. Our expert for the first case will be Dr. Todd Hollon. He's a neurosurgeon at the University of Michigan. Our first presenting author is Dr. Daniela Hurtado. Daniela is on staff at Mayo Clinic in Jacksonville, Florida. Her case report is entitled, A False Pituitary Tumor. Daniela, welcome, and we're looking forward to hearing about your case. Thank you very much, Dr. Young. I'm very excited to present this case on behalf of my co-authors, A False Pituitary Tumor. The reason for referral was a pituitary tumor at the Mayo Clinic endocrinology consultation service in Rochester, Minnesota. This was a 24-year-old male who was referred to our clinic for a pituitary tumor discovered during evaluation of progressively worsening headaches. The history of present illness goes as follows. He has had these headaches for at least five years. It was a pressure type of pain, diffuse, but more predominant behind the eyes. He also reported positional or orthostatic headache that was precipitated by activity and also worse in the afternoon, which also goes with the positional characteristic of this pain. The headaches were accompanied by photophobia, blurry vision, nausea, and projectile vomiting, and they were so severe that they were affecting his quality of life. In terms of his past medical and surgical history, eight years prior to his presentation, he had a C7 to T1 nerve schwannoma resection that was subsequently followed by a spinal fusion from C6 to T1. Seven years prior to his presentation, that is one year from his initial surgery, he was found to have spinal instrumentation failure that required fusion extension from C4 to T3. During that time, he was also admitted for a wound revision for poor wound healing. On review of systems, he reported intentional weight loss of 60 pounds in the one year preceding his presentation, mostly due to dietary changes and increased physical activity. He reported no visual field deficits, and he also reported no symptoms of pituitary hormone excess or deficiency. His physical exam was pretty unremarkable. He had normal vital signs. He had no signs of pituitary hormone excess or deficiency, and he also had no visual deficits on confrontation. The evaluation before his presentation included a brain MRI that identified a pituitary tumor by report. What did we do? At Mayo Clinic, we repeated a pituitary MRI with and without intravenous contrast that revealed a mildly enlarged and diffusely enhancing pituitary with rounded convexity of the superior margin, as shown with the white arrows. Additional findings included downward shift of the mammillary bodies, the pons, and cerebellar tonsils, shortening of the mid-sagittal width of the interpendicular fossa cistern, and partially effaced inferior portion of the fourth ventricle and cerebral aqueduct. All these findings were suggestive of intracranial hypotension and were not present in an MRI from eight years ago. The laboratory workup was remarkable for normal IGF-1, normal prolactin, FSH, LH, and testosterone, TSH, and free T4, ACTH, and cortisol levels. We consulted neurosurgery, and in the presence of his history of orthostatic headaches, prior spine surgeries, and imaging findings suggestive of intracranial hypotension, it was suspected that this young man had cerebrospinal fluid volume depletion syndrome manifesting as he presented. A few prior imaging revealed that he had evidence of extradural CSF accumulation in the spine, suggestive of CSF leak. This finding had been present since his one-year follow-up imaging after the initial spinal fusion and persisted at his two-year and three-year follow-up imaging. He also had evidence of brain sagging as early as one year after his spinal fusion. In the setting of his clinical presentation, diffuse pituitary gland enhancement without hormonal abnormalities, it was concluded that the pituitary gland findings on MRI were not a pituitary tumor, but rather a pituitary enlargement due to anatomical adaptation from CSF volume depletion. What was the treatment for our patient? Our patient underwent a dynamic computed tomography myelogram for CSF leak localization and repair. The myelogram revealed a CSF leak at the level of T1, T2, another at T3, and T5 vertebral body levels. The study guided placement of multilevel blood patches at these sites. After the procedure, the patient's headaches completely resolved in three days. Some special considerations in this case. His history of poor wound healing raised the possibility of connective tissue disorder that predisposes to a spontaneous CSF leak. Genetic testing was completed and was negative for relevant connective tissue disorders. Key takeaways. Consider a false pituitary tumor in patients presenting with pituitary enlargement without a hypo-enhancing lesion and imaging findings of intracranial hypotension. Patients usually present without pituitary laboratory abnormalities, and the cardinal symptom is orthostatic headache. Past medical and surgical histories should be reviewed if there is a high suspicion for CSF leak. Treatment for intracranial hypotension includes patching of the leaks after which symptoms and imaging abnormalities resolve. Thank you. Daniela, thank you so much for sharing that case with us. I think this is a key kind of case that any clinician seeing patients with pituitary disorders, we should know about. Dr. Adina Turcu, our deputy editor, is going to have the first question for you. Thank you, Daniela, for presenting this very interesting case. I was hoping you could highlight for the audience what other clinical scenarios, be it physiological or pathological, might present with an enhanced pituitary gland without a clear mass. That's a good question. So there are several reasons why a pituitary can be enlarged. And as you mentioned, they can be either physiologic or pathologic. From the physiologic perspective, we could see, for example, pituitary hyperplasia, pregnancy-related lactotroph hyperplasia, or sometimes thyrotroph or gonadotroph hyperplasia due to prolonged uncontrolled or untreated primary hypothyroidism and hypogonadism, respectively. Inflammation could lead to enhancement of the pituitary gland. Some malignancies with metastatic disease could also present with pituitary enlargement. This is a very broad differential diagnosis. So I would welcome the opinion of our guest expert, Dr. Todd Holland, who is an assistant professor of neurosurgical surgery at the University of Michigan, to share his thoughts about this case. Yes, so thank you for the invitation. This is a great case and very well managed, I will say. This is a situation where it's easy to sort of head down the wrong either diagnostic or interventional track and end up doing an operation where it wasn't needed. But you guys excellently avoided that. I think this case, from a neurosurgical and sort of structural anatomic perspective, really highlights the challenge of interpreting pituitary MRIs. There's just a lot of mimicking entities that we talk a lot about, but it can be quite challenging to really nail it like you guys did in this case. You know, it spans the full sort of diagnostic spectrum where you have inflammatory, infectious, neoplastic entities are all on the differential diagnosis. When you see something that doesn't look quite like a pituitary adenoma and you need to broaden that differential diagnosis. So this was an excellent catch. A real testament to you all and the neuroradiologists for identifying early the signs of intracranial hypotension. They can be very subtle. So things like the flattening of the corpus callosum. There was some flattening of the pons. And then the other thing that can really help is dilation of the dural venous sinuses and just the dura in general. So those are things that you can catch. But if you're not attuned to them or you're not thinking outside of the box in the sense that the patient has had a previous spinal fusion and is at risk for possible spontaneous CSF leak, they can be easily passed by. So, you know, it's really good to see that you identified this. One of the things that I will say as well is, you know, we're kind of in the habit of identifying anything that looks enlarged in the cella is just called a pituitary adenoma. And in this case, it was very clear. It was very homogeneously enhancing. And whenever I see that, I take a second to think, if it's a micro adenoma, we should see differential enhancement between the micro adenoma and the gland itself. And we really don't see that. And whenever I have a patient and I see something where the gland itself has more or less normal anatomy and you see the medial cavernous sinus walls and the overall anatomy of the pituitary gland looks like it ought to, just slightly bigger, I worry that this is not in fact an adenoma and may just be physiologic. So, again, this is a great teaching case and something that we can all take a lesson from. So, Daniela, I had a question for you. Before you had the neurosurgeon see the patient, did you know about this possibility of CSF leak as a presentation of a cellar mass? No, I definitely did not know this. And full disclosure, we do work pretty closely with our neurosurgery team. And what ended up happening is that as we were reviewing the images before the patient came, that's when Dr. Atkinson said, you know what, this doesn't look like a classic adenoma. Let me take a look at the prior imaging. And he was the one pretty much guiding us through this process. Apparently, for neurosurgeons, this is much more common than for endocrinologists. That was the first and my only case of a false pituitary tumor. I haven't seen any more of these cases. Well, thank you so much for sharing it with us today. Todd, you highlighted this presentation. I had a couple of questions for you with regard to this case and something I've never really understood. How does a blood patch actually, I mean, it fixed it like almost immediately in this patient. How does a blood patch actually work? Yeah, it's sort of shocking how well they work, especially when sometimes we can't even localize where the leak is. So some people can have fully idiopathic CSF leaks. And they usually are in the lumbar or the thoracic spine. In this case, you guys did an excellent workup. And I identified that the highest likelihood area was going to be the previous fusion sites. And we're able to identify that. But the idea is quite simple, is that you can sometimes actually just take the patient's blood. So you're actually going to use the patient's blood. Or there's actually fibrin glue, which we can use as well. And all it is is just finding the epidural, spinal epidural space. And just injecting this fibrin glue into that space in an attempt to form a small plug wherever that very small leak is. And they tend to be very small. And I can't quite recall in this case, but there's usually only a single leak. And the way to think about that, and this is the teaching in neurosurgery, is that if the faucet is on in one spot, all the other spots are going to close down, right? So if it's leaking from one spot, the whole pressure is going to be low with the exception of the one location where it's leaking. And that principle we use in endonasal surgery for the resection of pituitary adenomas. For example, if we get a CSF leak, a high-flow CSF leak in resecting a pituitary tumor or any sellar lesion, they're going to be leaking through their nose. And the justification for putting in a lumbar drain is if you're leaking in the lumbar region, you're not going to leak up here. So the same thing applies for the spontaneous CSF leaks, where if you can just find the one spot where it's leaking, and even a small amount of blood or fibrin glue usually seals it off. And then the patient usually recovers after a single blood patch. Excellent. I have a follow-up question, Todd. So when faced with a diffusely enlarged pituitary gland, and if the clinical and biochemical workup is negative for hormonal excess, suggesting that this is not a pituitary problem, when does biopsy have a role, and what are the risks of pituitary biopsy? Yeah, I may have a slightly lower threshold than your average neurosurgeon to proceed with a biopsy. And the reason is because I often feel very bad for patients when they're having usually some kind of significant clinical symptom that brings them to medical attention. It obviously depends on the lesion. But for example, if a patient has DI and has an enhancing lesion in the pituitary gland, or specifically the pituitary stalk, that's where I think something is going on here. Is it hypophysitis? Is it a Langerhans's cell histiocytosis? There's a lot of things that can cause that specific syndrome, that look where patients are in DI, they have a lesion. It doesn't look like a pituitary adenoma. And sometimes I feel bad just throwing steroids at them. And I think that that can sometimes cause a very long period of undertreatment. So in those instances, I have a very low threshold to just move forward with surgical biopsy. Where it's a little bit higher is if you have a young woman, or it's peripartum, and you think this is likely to be physiologic, you have a high suspicion ahead of time that this is going to be non-pathologic. And overall, the patient is doing okay, then I think you have some time just to conservatively watch this. But again, in this case, it was good that you guys moved on this because of the positional headaches, right? That is not normal. It's never normal to have positional headaches like that. So I certainly wouldn't want to tell this patient, the pituitary gland doesn't look great. I know you're suffering. See you in six months. That doesn't feel like a good thing to do. So in this case, I totally agree with doing the workup that you did. And it's good that you were able to identify it. And this is an instance where you could biopsy it. It wouldn't be the worst thing. But obviously, you've kind of bought this patient a surgery that they didn't really need if you had kind of pieced all of the clinical history and the radiographic findings together. Daniela, I have one last question for you. Now that you've gone through all this, you've had your first case of brain sag causing an apparent pituitary mass. What would you share with endocrinologists as two or three things within which we should really think about this as a possibility? Because, for example, in your case, the outside radiologist didn't give you the tip off. Right. And many radiologists may not. As Todd said, it could be fairly subtle. So when should we as endocrinologists say, hey, this might be what's going on? Right. So I think there were a couple of things that I took from this case. First of all, looking at the images, right? Many people will just look at the report. And when we look at the images and we try to understand, you know, in general, the anatomy, we don't need to be a radiologist. But once Dr. Atkinson actually pointed out those specific signs of low intracranial pressure, then I was like, oh, it makes sense. And I started comparing images. That's the other thing. Comparing normal versus what may be abnormal kind of guided me to understand better what I can look when I look at pituitary or brain MRIs. So that's the first one. And then the second one is exactly what has been mentioned, right? This was a diffuse enhancement. There wasn't a hypo-enhancing lesion suggesting of a pituitary adenoma. And based on the history, this is the person that besides the headaches that have become debilitating, he didn't really have any other symptoms, any other signs. So I think the holistic approach to this case is very important. And that's generally how it works for endocrinology cases. Once one endocrine organ is affected, we can truly see signs and symptoms everywhere in the body. So just be mindful about that. Look at the images and do a very good clinical history to understand what the risk factors could be as well. Thank you, Daniela. Adina? I wanted to follow up with a question for both Daniela and Todd. So your case did not have any hormonal deficiency, but since us endocrinologists are not very familiar with this orthostatic intracranial or intracranial hypotension, do we know if through mechanical pooling, hormonal insufficiency is ever a possibility in these cases? So from my literature review, there isn't much. So generally, they do not present with hormonal abnormalities. But as I think through this case, if it is enough mechanical pressure from the pooling down, I think that's possible. The other way of thinking about this is the opposite, right? When patients have intracranial hypertension, they can have these partially empty sella presentation on imaging. And there are some patients that could potentially develop some deficiencies or abnormalities, but there wasn't much on the literature that I could find. Yeah, I would second that. The only thing I could imagine is kind of hyperprolactinemia, because that seems to be anything kind of subtle wrong with the pituitary. That's kind of one of the first things to go. But I haven't heard of anything definitive related to this. Well, I want to thank Daniela for sharing her case with us today. I want to thank Todd for being our content expert and giving us some great pearls to take forward. And Adina and I thank you all for joining us to discuss this presentation. Thanks, everybody. Thank you.

webinar

Dr. Daniela Hurtado

case report

false pituitary tumor

intracranial hypotension

CSF leak