Rapid-Fire Clinical Pearls (May 2026 - Part 2)

While not every case can make the cut each month and be considered one of my favorites, many still have interesting clinical pearls and lessons worth sharing.

Here’s a collection of some of my favorite additional pearls from May 2026.

I’ve broken this into a few separate posts to keep the length more manageable.

Ovarian Leydig cell tumors secrete androgens.

They are a cause of hyperandrogenism and virilization in post-menopausal women

Clinical presentations usually involves hirsutism, androgenic alopecia, a deepening voice, and clitoromegaly. Although onset is often rapid, it can also develop slowly over many years.

Key labs include elevated serum testosterone, often greater than 150 ng/dL, but normal levels of adrenal androgen, such as DHEA-S. This combination of lab findings helps localize the source of the ovaries.

While imaging can identify a solid ovarian mass, Leydig cell tumors are often very small (less than 1 cm) and within normal ovarian stroma, which can lead to a “negative” study.

The definitive diagnosis of a Leydig cell tumor requires the identification of Reinke crystals.

Source: Annals of IM - Postmenopausal Occult Ovarian Disease With Hirsutism – A 6-Year Follow-Up Course

Clopidogrel is a prodrug requiring hepatic CYP450 enzyme activation (primarily CYP2C19).

Genetic differences can lead to a “nonresponder” or “hyporesponder” state.

In these patients, usual doses of clopidogrel won’t be effective and thus increase the risk of thrombosis after receiving a stent until there has been adequate endothelialization (which can take weeks to months).

Platelet function testing can test for reduced platelet inhibition from clopidogrel.

In such cases, future anti-thrombotic medication should prioritize alternative options like ticagrelor or prasugrel rather than re-challenging with clopidogrel.

Source: Annals of IM - Clopidogrel Nonresponsiveness Mimicking Endocarditis After PFO-Occlusion Combining Aspiration, Retrieval, and Laboratory Assessment for Diagnostic-Therapeutic Work-Up

Osteonecrosis (also known as avascular necrosis, or AVN) is ischemic death of bone tissue resulting from poor blood supply. It commonly affects the femoral head.

Though it’s often linked to trauma, corticosteroids, and alcohol, it can also rarely be caused by anti-angiogenic medications such as bevacizumab (Avastin).

Bevacizumab inhibits vascular endothelial growth factor (VEGF) which promotes the formation of blood vessels.

Thus, blocking this pathway impairs perfusion and repair of bone, increasing the risk of osteonecrosis.

Patients will usually present with slow onset of joint pain over time that worsens with weight-bearing.

MRI is best for diagnosing osteonecrosis since it’s highly sensitive for early changes such as “bone marrow edema”, “subchondral signal abnormalities”, and eventually “articular surface collapse”.

Source: Annals of IM - Bevacizumab-Associated Osteonecrosis Of The Femur

Migration of a transjugular intrahepatic portosystemic shunt (TIPS) stent is rare but can be a potentially fatal complication. It can happen if the stent dislodges and embolizes cranially into the right atrium, right ventricle, or pulmonary artery.

Migration of the stent can cause arrhythmias from direct myocardial irritation, TR, perforation with tamponade, and clot/PE.

Source: Annals of IM - Intracardiac Migration Of A Tips Stent Causing Ventricular Tachycardia

The classic presentation of GBS is a rapidly progressive, relatively symmetric ascending weakness that begins in the feet and legs and moves upwards over hours to days.

Flaccid paralysis is the classic finding. It can progress to involve the trunk, upper limbs, cranial nerves, and respiratory muscles, potentially leading to respiratory failure.

Vital capacity (FVC) and negative inspiratory force (NIF) can help you anticipate the need for intubation.

Another sign is areflexia or hyporeflexia.

Paresthesia in the hands and feet is common. Significant sensory loss is not typical.

Autonomic dysfunction, including tachycardia, arrhythmias, labile blood pressure, and urinary retention, can occur in many patients.

The classic CSF finding is “albuminocytologic dissociation”, which means there’s an elevated protein with a normal WBC count. However, this might be absent in the first one to two weeks of illness.

Source: CPS - May 4, 2026 Mainstream Mondays VMR with Youssef & Saketh - B/L lower limb weakness

The classic presentation involves cognitive impairment (such as short-term memory deficits) behavioral or psychiatric disturbances, and seizures.

Facial brachial dystonic seizures are essentially pathognomonic for LGI1 encephalitis.

Autoimmune encephalitis can present with a completely normal CSF analysis. A bland CSF does not rule out an inflammatory process.

The onset of hyponatremia in a patient with neuropsychiatric symptoms should raise suspicion for limbic encephalitis, since it’s a common paraneoplastic or autoimmune-related SI/ADH finding.

Source: CPS - May 6, 2026 VMR with Steph & Zaven - 3 months involuntary movements and behavioral changes

Around 85% of patients diagnosed with CML are diagnosed in the “indolent chronic phase.” CML is often discovered incidentally. When the patient is symptomatic, they might present with fatigue, weight loss, or LUQ discomfort due to splenomegaly.

The combination of splenomegaly (even when noted incidentally on imaging) and a high WBC should raise suspicion.

The presence of basophilia in a left shift that spans across all myeloid cells are classic findings in CML.

In the setting of significantly elevated WBC from CML, inflammatory markers (CRP/ESR) can be normal. This can be a key negative finding that can help differentiate from a severe reactive or infectious process.

Source: CPS - May 11, 2026 Mainstream Mondays VMR with Maddy & Seeme - worsening depression and suicidal attempt

An aleukemic (or leukopenic) variant of ALL can happen when blasts are not seen peripherally and are only in the marrow. This can delay diagnosis, given the classic picture of a high WBC seen on CBC is missing.

The combination of massive splenomegaly and cytopenias (especially plts less than 20,000-30,000) suggests primary marrow failure since hypersplenism alone is unlikely to cause such severe deficits.

An elevated ALP that is seemingly out of proportion to the level of transaminases can be a major clue for malignant infiltration in the liver, especially if there is hepatomegaly.

Source: CPS - May 12, 2026 VMR with Ravi & Kirtan - fever, yellow discoloration of eyes, epistaxis

“Synpharyngitic” hematuria (gross hematuria seen during a URI, or shortly afterward) is consistent with IgA nephropathy. This distinguishes it from post-streptococcal glomerulonephritis, which usually doesn’t present until one to three weeks after infection.

The combination of hematuria, proteinuria, and casts on a UA is considered “nephritic sediment”. The presence of the sediment helps to localize the pathology to the glomerulus.

Patient diagnosed with IgA nephropathy should also be asked about rash, joint pain, and abdominal pain which may prompt concern for IgA vasculitis.

Source: CPS - May 18, 2026 Mainstream Mondays VMR with Maddy & Magnus - reddish discoloration of urine