This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.
I’ve broken these cases into multiple parts to keep the length of each post more digestable.
Case Summary
A 28F presented with three days of dysuria along with gross hematuria and right flank pain. Together, these were suggestive of complicated nephrolithiasis. CT revealed bilateral nephrolithiasis and a right ureteral stone. However, labs are also notable for calcium 11.8 mg/dL with a PTH of 145. Together, these were evidence of primary hyperparathyroidism. On further intake, the patient also reported chronic fatigue, constipation, and irregular menses. Additional workup uncovered high prolactin (120 ng/mL). On even further questioning, the patient revealed a family history of endocrine tumors. The patient was ultimately diagnosed with multiple endocrine neoplasia type 1 and (MEN 1). Imaging confirmed a 1.4 cm pituitary macroadenoma. She was started on a dopamine agonist.
Multiple Endocrine Neoplasia Type 1 (MEN1)
MEN1 (also known as Wermer’s syndrome), is it an autosomal dominant disorder caused by mutations in the MEN1 tumor suppressor gene. As you likely recall from your STEP days, it is characterized by the development of tumors in the “three Ps”: parathyroid, pituitary, and pancreas (or duodenum).
The most common manifestation in over 90% of cases is primary hyperparathyroidism. This is also the earliest manifestation. Patients will often present with hypercalcemia or hypercalcemia-related symptoms, including nephrolithiasis, bone pain, constipation, or fatigue. Pituitary adenomas are the next most common, and prolactinomas are the most frequent type. Prolactinomas can cause amenorrhea, galactorrhea, or decreased libido. Pancreatic neuroendocrine tumors (pNETs) include gastrinomas (which cause Zollinger-Ellison syndrome), insulinomas, VIPomas, and non-functioning tumors.
In patients with suspected MEN1, a full endocrine screen should be sent. This includes prolactin, gastrin, IGF-1, insulin, and glucose to screen for the classic “P” tumors.
Once a biochemical diagnosis is made, imaging is needed to help localize tumors. Neck ultrasound or sestamibi scans can evaluate parathyroid glands. Pituitary MRI is the best modality to assess for adenomas. CT or MRI of the abdomen is most commonly used to screen for pNETs.
However, the final diagnosis of MEN1 is confirmed with genetic testing.
Prolactinomas are treated medically with dopamine agonists. Management of hyperparathyroidism in MEN1 is complicated. These cases often involve asymmetric 4-gland parathyroid hyperplasia whereas sporadic cases will have a single adenoma that can simply be removed. All of the parathyroids will often be removed with auto-transplantation. Some patients will need medical therapy with cinacalcet.
All patients with MEN1 will require lifetime imaging surveillance for new tumors.
Pearls
Vague systemic symptoms like fatigue or constipation, along with an endocrine abnormality such as irregular menses should raise suspicion. The addition of kidney stones should further raise the suspicion, given likely underlying hypercalcemia.
In patients diagnosed with endocrine tumors at a young age, a detailed family history can be critical given it may change surgical planning for hyperparathyroidism due to four-gland hyperplasia and not a single adenoma that can simply be removed
Chronic hypercalcemia can mimic IBS, particularly the constipation-predominant type. Before formally diagnosing IBS, you should always check a calcium level.
Patients with recurrent kidney stones should always have a BMP checked to rule out metabolic causes like hypercalcemia which may lead to further diagnoses
My Commentary
The the very first rotation I ever did during my clerkship year was with an endocrine oncology surgical team. Thus, I have a particular affinity for these unusual endocrine tumors and the nuances of their management. It was an amazing first clinical experience. Although it made me assume that zebras (pheochromocytomas, gastrinomas, insulinomas, MEN1, etc.) are much more common than they are!
This case is particularly interesting because it unfolded in a realistic manner. In my opinion, it highlights how most atypical or rare diseases are ultimately diagnosed. Many case reports will organize information plainly in a streamlined manner, leading us to assume the clinicians went through the diagnostic process in a stepwise manner to arrive at the final diagnosis. However, the reality is that unexpected laboratory and imaging findings will often lead clinicians to pause and go backwards to further clarify history with the patient which then helps them arrive at the diagnosis. Although we were taught in medical school to do a thorough family history and complete a full ROS, in reality, this does not happen. I don’t say this to imply that clinicians (myself included) are lazy, but rather than effective, focused history, exam, and diagnostic workups focus on likely and life-threatening etiologies. When data is introduced that is unexpected or changes the clinical picture, good clinicians will not disregard it but rather will investigate further and not be afraid to move backwards.
I distinctly recall a case of a patient diagnosed with Pasteurella bacteremia when I was a resident. Only after the blood cultures returned positive did I ask the patient if she had any pets or recent bites. She revealed that she did in fact have a new puppy, and showed me a very small, healing red cut on the inside of her index finger. She sheepishly added “he didn’t mean to - he was just playing!” All’s well that ends well.
The case is also a great reminder that some nondescript or common symptoms, such as fatigue, constipation, irregular menses may individually not be particularly notable. However, if such symptoms are persistent, it’s important to think through how they interact and what a common root cause might be. This can be particularly challenging in patients that report many disparate seeming symptoms.
Case Summary
A 56M presented with a number of recurrent ischemic strokes and was found to have progressive upper extremity weakness. These findings were initially attributed to mild carotid plaque. However, his neurological status deteriorated despite antithrombotic therapy. Imaging revealed new scattered infarcts and progression of his right internal carotid artery (ICA) plaque to severe stenosis with occlusion. He had a workup for cryptogenic stroke completed. It was notable for a serum IgG4 level of 2050 mg/dL (very high). Subsequent PET scan showed multifocal hypermetabolism in the Waldeyer ring and cervical lymph nodes. The patient had a tonsillar biopsy that confirmed the diagnosis, showing a dense lymphoplasmacytic infiltrate with IgG4/IgG >40%. He was treated with IVIG and glucocorticoids, then mycophenolate mofetil (MMF). The patient showed partial functional recovery.
IgG4-Related Disease (IgG4-RD)
IgG4-Related Disease is a systemic immune-mediated fibroinflammatory condition with tumefactive lesions that result from the infiltration of IgG4-positive plasma cells into different organs in the body. Classic presentations typically involve the pancreas, salivary or lacrimal glands, and retroperitoneum. However, essentially any organ can be affected by the disease. Patients with neurological involvement will often present as hypophysitis. Synovitis of the intracranial arteries due to large vessel vasculitis is rare in this disease but does happen.
Workup starts with a serum IgG4 concentration. A level >135 mg/dL is consistent with the diagnosis. However, note that this lab is neither 100% sensitive nor specific.
CT or MRI might show organ enlargement or mass-like lesions. If the patient has a concomitant vasculitis, vessel wall imaging might reveal concentric enhancing wall thickening, which will appear different from typical atherosclerosis. A PET can be extremely useful to identify occult sites of inflammation and help guide biopsy.
Histopathology will show lymphoplasmacytic infiltrate, “storiform” fibrosis, and “obliterative phlebitis”. Immunohistochemistry will help confirm the diagnosis by showing >10 IgG4-positive plasma cells per high-power field. Importantly, the IgG4 to IgG cell ratio will exceed 40%.
Glucocorticoids are first-line therapy, which will often lead to rapid responses. Rituximab or MMF are then frequently used for maintenance therapy or in cases where steroids are not working.
Pearls
IgG4-RD should be considered in the ddx for cryptogenic stroke. Clues can be stroke in patients with multifocal or atypical large vessel vasculopathy who do not have traditional atherosclerotic risk factors.
Although an elevated serum IgG4 is a major clue, the diagnosis requires a biopsy, since other inflammatory malignant conditions can also raise the IgG4 levels.
PET scans are especially useful for helping identify biopsy sites. Salivary glands and superficial lymph nodes are easily accessible and often high-yield.
In patients with vascular stenosis who progress despite typical antiplatelet or AC therapy, you should consider an underlying inflammatory vasculitis.
Treatment with immunosuppression not only halts progression but can also reverse stenosis.
My Commentary
IgG4-RD is one of those confusing diseases that internal medicine physicians (myself included) love to bring up on their differential. In my experience, working up cryogenic strokes with multifocal scattered infarcts across different vascular territories, it’s almost always been in the setting of occult malignancy like pancreatic cancer. This makes sense simply given the prevalence of the underlying causative diseases (malignancy is much more common than IgG4-RD) . But it’s important to remember that any prothrombotic or inflammatory disease can lead to similar outcomes. When we’ve had a high clinical suspicion for IgG4-related disease in patients I have cared for, I don’t know that the diagnosis was ever truly a slam dunk, even after biopsy. This might be due to the pearl above that IgG4 can be elevated in other inflammatory or malignant conditions.
Case Summary
A 61F with no notable PMH presented in septic shock with severe epigastric abdominal pain and N/V. Despite this, she had no urinary symptoms, and an exam did not show any CVA tenderness. However, UA showed significant pyuria and positive nitrates. CTAP showed a horseshoe kidney with a large obstructing right ureteropelvic junction stone. Despite this, there was only mild to moderate hydronephrosis. The patient recovered after fluid resuscitation, abx, and an emergent PCN for urinary decompression.
Obstructive Urosepsis in a Horseshoe Kidney
Obstructive urosepsis is a life-threatening emergency where UTI is complicated by a blockage and leads to sepsis. The obstruction prevents clearance of infected urine. This leads to pressure building up in the collecting system and facilitates bacterial translocation into the bloodstream. A horseshoe kidney is a congenital disorder where the kidneys are fused at their lower poles, which creates a U-shape. Horseshoe kidneys lead to unusual ureteral courses and change the angle of insertion, which can predispose patients to urinary stasis. This leads to increased risk of nephrolithiasis and obstruction.
Fever, chills, and flank pain are classic signs of sepsis from a urinary source. However, presentations in patients with horseshoe kidneys may be atypical. Such patients may present with abdominal or epigastric pain and lack clear urinary symptoms.
Management requires prompt BSA and urgent urinary decompression to achieve source control. This is most typically achieved with a PCN or ureteral stenting.
Pearls
In patients with unusual urinary anatomy, infections may present atypically without GU symptoms. The abnormal position and visceral innervation of a horseshoe kidney can refer pain to the mid-abdomen or epigastric region and present more like pancreatitis
The degree of dilation in hydronephrosis does not always correlate with the severity of an infection; you should not be falsely reassured by a mild to moderate hydronephrosis.
My Commentary
I like this case because it reminds me that patients can still present with sepsis from a urinary source even if they don’t have clear urinary symptoms. In my experience, this most commonly happens in elderly patients, or in those that have unusual anatomy (congenitally, or surgically) or indwelling lines. The latter can be particularly challenging because their urine will often show pyuria due to inflammation from foreign material. More often than not, in my clinical experience, I face the opposite problem: patients with pyuria and positive UCx who do not seem to have any clinical symptoms. I actually feel this might be a more challenging clinical situation because in patients who present with evidence of sepsis or septic shock, you are going to always treat with antibiotics anyway. In clearly ill patients, the real clinical challenge, as this case shows, is to recognize that patients won’t improve without source control and thus, imaging of the abdomen in patients that don’t otherwise have a clear source can be critical to help guide management and potentially save a life.
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