Cushing’s syndrome can cause seizures, though it does so through several indirect pathways rather than one straightforward mechanism. Excess cortisol affects the brain in ways that lower the threshold for seizure activity, and the metabolic complications of the syndrome, from dangerously high blood pressure to electrolyte imbalances, each carry their own seizure risk. Case reports document seizures as a presenting symptom in both children and adults with Cushing’s, and the picture gets even more complicated when treatments for the syndrome introduce their own neurological side effects.
How Excess Cortisol Shifts the Brain Toward Seizures
Cortisol is a glucocorticoid, and the brain is densely packed with receptors for it, particularly in the hippocampus, a region already prone to generating seizure activity. Research in animal models has consistently shown that glucocorticoids lower the threshold at which neurons begin firing uncontrollably. They make evoked seizures worse, speed up the process by which the brain becomes progressively more sensitive to seizure triggers, and amplify the neuronal damage caused by prolonged seizure episodes.1PubMed Central. Hippocampal glucocorticoid receptors modulate status epilepticus severity In plain terms, flooding the brain with cortisol for weeks or months, which is exactly what Cushing’s syndrome does, makes the brain more electrically unstable.
The relationship is not perfectly linear, though. In experiments that selectively reduced glucocorticoid receptors in the hippocampus, mild behavioral seizures actually appeared sooner, while more severe convulsive seizures and death were delayed in male mice.1PubMed Central. Hippocampal glucocorticoid receptors modulate status epilepticus severity This suggests that the role of cortisol in seizures is nuanced: at certain levels it may suppress the progression to the most dangerous forms of seizure, while at chronic excess it generally pushes the brain toward instability. For someone living with Cushing’s, the takeaway is that chronic cortisol overproduction creates a brain environment where seizures become more likely, even if the person has no history of epilepsy.
When Blood Pressure Spikes Cause Brain Swelling
One of the most dramatic ways Cushing’s syndrome leads to seizures is through a condition called posterior reversible encephalopathy syndrome, or PRES. This happens when severely elevated blood pressure overwhelms the brain’s ability to regulate its own blood flow, causing fluid to leak into brain tissue, especially in the back of the brain. The result is swelling that produces headaches, confusion, vision problems, and seizures.
Cushing’s syndrome frequently causes significant hypertension because cortisol promotes sodium and water retention and increases the sensitivity of blood vessels to other hormones that raise blood pressure. In some patients, the hypertension becomes severe enough to trigger PRES. One case series noted that PRES had been reported in at least six patients with Cushing’s syndrome, with severe secondary hypertension suspected as the trigger.2PubMed Central. A Case of Cushing’s Disease Presenting with Posterior Reversible Encephalopathy Syndrome In one pediatric case, a child with a type of adrenal Cushing’s presented to the emergency department with a new-onset seizure and high blood pressure, and brain imaging confirmed findings consistent with posterior encephalopathy.3PubMed Central. Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome
The “reversible” part of PRES is important. When the blood pressure is brought under control and the underlying cortisol excess is addressed, the brain swelling typically resolves and the seizures stop. But if the condition goes unrecognized and untreated, it can progress to permanent brain injury. PRES should be on the radar of any clinician managing a patient with Cushing’s who develops sudden neurological symptoms, and for patients themselves, a sudden severe headache with visual changes or confusion is a reason to seek emergency care.
Blood Clots and the Brain
Cushing’s syndrome puts people in a prothrombotic state, meaning their blood clots more easily than it should. Deep vein thrombosis in the legs and blood clots traveling to the lungs are well-recognized complications.4World Neurosurgery. Cerebral Venous Sinus Thrombosis After Transsphenoidal Resection: A Rare Complication of Cushing Disease-Associated Hypercoagulability Less commonly, clotting can happen in the veins that drain blood from the brain, a condition called cerebral venous sinus thrombosis. When blood cannot drain properly from the brain, pressure builds, and that rising pressure can cause headaches, vision changes, and seizures.
Cerebral venous sinus thrombosis is much rarer than clotting in the legs, but it is particularly dangerous because its symptoms can mimic other neurological emergencies. The heightened clotting tendency in Cushing’s comes from cortisol’s effects on several clotting factors and on the cells lining blood vessels. This risk persists even after surgical treatment and is actually elevated in the immediate postoperative period, which is why many surgical centers use blood-thinning medications around the time of tumor removal.
Seizures as a Presenting Symptom in Children
Cushing’s syndrome is rare in children, and when it does occur, the presentation can look quite different from what doctors expect. One reported case involved a six-year-old boy who came to medical attention with generalized body swelling, a round face, acne, weight gain, dark patches on his skin, high blood pressure, and seizures.5Journal of Association of Clinical Endocrinologist and Diabetologist of Bangladesh. Generalized swelling and convulsions in a 6-year-old boy: Atypical presentation of ectopic Cushing syndrome His Cushing’s turned out to be caused by a tumor outside the pituitary gland producing excess hormone, what is called ectopic Cushing syndrome.
In pediatric cases, the combination of rapidly developing hypertension, electrolyte shifts, and a still-maturing brain may make seizures more likely than they are in adults. Children also tend to present later in the disease course because the early signs, like weight gain, can be attributed to normal childhood growth patterns or other more common conditions. By the time Cushing’s is diagnosed, the cortisol excess may have been present long enough to produce serious complications including seizures. For parents and pediatricians, the lesson is that unexplained seizures combined with rapid weight gain, high blood pressure, or unusual physical changes like dark skin patches or facial rounding should prompt consideration of an endocrine cause.
When the Seizures Are Not What They Seem
Not every seizure-like event in a patient with Cushing’s is an actual epileptic seizure. Cushing’s syndrome carries a heavy psychiatric burden, including depression, anxiety, psychosis, and cognitive decline. In some cases, the psychological strain produces what are called functional neurological symptoms, episodes that look like seizures but have no underlying electrical brain abnormality.
One well-documented case involved a patient with Cushing’s disease who developed multiple functional neurological symptoms, including nonepileptic seizures, paralysis in both legs, reduced hand function, and a stutter.6PubMed Central. Cushing’s Disease Presenting with Functional Neurological (Conversion) Disorder These were genuine symptoms that caused real disability, but they were driven by the way the brain was processing the extreme hormonal and psychological stress of the disease rather than by abnormal electrical discharges.
Distinguishing epileptic seizures from nonepileptic events is critical because the treatment is completely different. Antiseizure medications will not help nonepileptic seizures and may cause unnecessary side effects. The distinction usually requires EEG monitoring during an episode. For someone with Cushing’s who is experiencing seizure-like events, getting the right diagnosis matters enormously, because the solution may involve treating the underlying cortisol excess and providing psychological support rather than adding anticonvulsant drugs.
What Brain Recordings Actually Show in Cushing’s
Researchers have looked at the electrical activity of the brain in people with Cushing’s syndrome using standard EEG recordings. In many cases, the recordings came back normal or showed only minor abnormalities: slight slowing of background activity, some disorganization, and occasional sharp waves or small spike-wave patterns.7PubMed. EEG changes and serum cortisol levels in Cushing’s syndrome Excessive fast activity was also noted in some patients.
These findings are subtle enough that they would not, on their own, lead to a diagnosis of epilepsy. But they do suggest that chronic cortisol excess creates a low-grade shift in how the brain’s electrical circuits behave. The sharp waves and spike-wave discharges are the same types of activity seen in people with seizure disorders, just at a lower intensity. Think of it as the brain sitting closer to the edge of electrical instability without necessarily going over it. In the right circumstances, an additional push, from a spike in blood pressure, a drop in sodium levels, or severe sleep deprivation, could tip that borderline brain activity into a full seizure.
Seizure Risks That Come with Treatment
Paradoxically, treating Cushing’s syndrome can also introduce seizure risks. The most common surgical treatment for pituitary-driven Cushing’s is transsphenoidal surgery, where a surgeon removes the pituitary tumor through the nose. After the procedure, patients frequently develop delayed drops in blood sodium levels. In one study of 241 patients who had routine sodium levels checked a week after surgery, about 23% were found to have low sodium, and roughly 5% developed symptoms from it.8Journal of Neurosurgery. Recognition and management of delayed hyponatremia following transsphenoidal pituitary surgery When sodium drops low enough, the brain swells, and seizures are one of the most concerning consequences.
This post-surgical sodium drop typically happens around days five through nine after the operation, which is often after the patient has already gone home. That timing makes it easy to miss if patients are not warned to watch for symptoms like headache, nausea, confusion, or lethargy. Most surgical centers now routinely check sodium levels after pituitary surgery and educate patients on warning signs, but it remains a genuine hazard.
Medications used for Cushing’s can also create neurological problems. Mitotane, a drug used primarily for adrenal cancer that sometimes accompanies Cushing’s syndrome, has well-known neurological side effects at higher doses. In one pilot study of patients on mitotane therapy, EEG recordings revealed epileptic abnormalities in a patient whose blood levels of the drug had been above the therapeutic threshold for over two years.9PubMed Central. Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study The drug can also cause slowed thinking, memory problems, confusion, muscle tremors, and dizziness. For patients on mitotane, regular neurological monitoring and drug-level checks are important for catching these issues before they escalate.
Sleep Disruption and Its Relationship to Seizure Vulnerability
Sleep and seizures have a well-established link outside of Cushing’s: sleep deprivation is one of the most reliable triggers for seizures in people with epilepsy, and disrupted sleep architecture can lower the seizure threshold even in people without a seizure history. Cushing’s syndrome is notorious for wrecking sleep. Over half of patients with active disease report insomnia or significantly disrupted sleep, and roughly two-thirds say they often or always have trouble sleeping.10PubMed Central. Sleep disruption in patients with active and treated endogenous Cushing’s syndrome
The disruption comes from multiple directions. Cortisol normally follows a circadian rhythm, peaking in the early morning and dropping at night, and that rhythm is part of what helps the brain transition into and maintain sleep. In Cushing’s, the normal rhythm is flattened or abolished, with cortisol levels remaining high through the evening and nighttime hours. The result is difficulty falling asleep, frequent awakenings, and poor-quality sleep overall. Add in the anxiety and depression that accompany the disease, and some patients end up chronically sleep-deprived.
Even after successful treatment, sleep problems persist for many patients. About 42% of people with treated Cushing’s still report frequent trouble sleeping, and around 31% continue to use sleep medications.10PubMed Central. Sleep disruption in patients with active and treated endogenous Cushing’s syndrome For someone whose brain is already electrically primed by chronic cortisol exposure, ongoing sleep deprivation represents one more factor pushing toward seizure susceptibility. Addressing sleep directly, whether through behavioral strategies, medication adjustments, or treatment of any remaining cortisol excess, is an underappreciated part of managing seizure risk in these patients.
Why the Pathway Matters for Treatment Decisions
If you or someone you know with Cushing’s syndrome experiences a seizure, the most important question is not just “why did it happen” but “which pathway caused it,” because the answer determines what to do next. A seizure from PRES calls for urgent blood-pressure management and possibly imaging to confirm the diagnosis. A seizure from post-surgical low sodium requires careful sodium correction, not antiseizure drugs. A seizure-like event that turns out to be a functional neurological symptom needs psychological treatment and cortisol control, not anticonvulsants. And seizure activity triggered by a medication like mitotane may resolve with dose reduction.
In practice, the evaluation usually starts with basic blood work (sodium, potassium, calcium, glucose), blood pressure measurement, a brain scan to rule out structural problems like clots or PRES, and an EEG to characterize the electrical activity. If the seizure occurs in the post-surgical window, sodium levels are the first thing to check. If it occurs during active, untreated disease, hypertension-driven PRES and the direct effects of cortisol on brain excitability are higher on the list.
The encouraging piece is that most seizure pathways in Cushing’s syndrome are treatable or even reversible once the underlying driver is identified. PRES resolves with blood-pressure control. Post-surgical hyponatremia corrects within days. Medication-related seizures improve with dose adjustment. And as cortisol levels normalize with definitive treatment, the brain’s electrical environment gradually stabilizes, reducing the long-term seizure risk that chronic cortisol excess creates.