Cushing’s Syndrome is a hormonal disorder characterized by prolonged exposure to high levels of cortisol. This excess cortisol can lead to various physical and mental changes. While many symptoms are well-known, its potential connection to seizures is less commonly discussed. This article explores the relationship between Cushing’s Syndrome and seizure activity, examining how this hormonal imbalance might contribute to neurological manifestations.
Understanding Cushing’s Syndrome
Cushing’s Syndrome arises from excessive cortisol levels over an extended period. Cortisol, often called the “stress hormone,” plays a crucial role in regulating blood pressure, maintaining blood sugar, reducing inflammation, and converting food into energy. The most frequent cause is the long-term, high-dose use of glucocorticoid medications, which mimic cortisol and are prescribed for inflammatory conditions.
Internal causes include tumors. A common cause is a benign growth in the pituitary gland, located at the base of the brain, leading to excessive ACTH production. ACTH then signals the adrenal glands, situated atop the kidneys, to produce too much cortisol. Adrenal gland tumors directly producing cortisol, or ectopic ACTH-producing tumors found elsewhere, can also cause the syndrome.
Physical signs of Cushing’s Syndrome include gradual weight gain, particularly around the trunk, with thinner arms and legs. Other common symptoms are a rounded, reddened face, easy bruising, and wide purple stretch marks on the skin. Individuals may also experience muscle weakness and fatigue.
The Direct Link: Cushing’s and Seizures
While not among the most common neurological symptoms, Cushing’s Syndrome can contribute to seizure activity. Seizures were reported in approximately 6% of patients with Cushing’s presenting with neuropsychiatric symptoms. This connection involves several physiological mechanisms influenced by prolonged cortisol excess.
High blood pressure, affecting 70-85% of adult patients, is a significant factor. Chronic hypertension increases the risk of cerebrovascular events like strokes or transient ischemic attacks (TIAs), which can trigger seizures. Posterior Reversible Encephalopathy Syndrome (PRES), a severe neurological complication characterized by headaches, altered mental status, visual changes, and seizures, has also been reported in Cushing’s patients, often with severe hypertension.
Electrolyte imbalances also play a role, particularly hypokalemia (abnormally low potassium levels). Hypokalemia is a recognized feature of Cushing’s Syndrome, especially in cases caused by ectopic ACTH-producing tumors. Low potassium levels can alter neuronal excitability and lower the seizure threshold, making the brain more susceptible to abnormal electrical activity. A case report highlighted refractory convulsive epileptic seizures linked to severe hypokalemia in a patient with paraneoplastic Cushing’s Syndrome.
High cortisol levels can directly impact brain function. Studies indicate that individuals with frequent seizures often have elevated basal cortisol levels, and cortisol levels tend to rise following a seizure, suggesting that cortisol may reduce the seizure threshold. Research in animal models shows that elevated cortisol can increase excitatory activity in brain regions like the hippocampus, making neurons more prone to firing excessively and triggering seizures. Chronic stress, characterized by sustained high cortisol, has been associated with increased seizure susceptibility.
Cushing’s Syndrome can also lead to metabolic disturbances, such as hyperglycemia (high blood sugar). While not always a direct trigger for seizures, severe fluctuations in blood sugar levels can induce seizures in susceptible individuals. The complex interplay of these factors underscores how the hormonal disruption in Cushing’s Syndrome can create an environment conducive to seizure activity, even if it remains a less common manifestation compared to other neurological issues like mood disturbances or cognitive decline.
Recognizing and Addressing the Issue
Recognizing a potential link between Cushing’s Syndrome and seizures is important for effective medical intervention. Anyone experiencing new-onset seizures, especially if accompanied by other signs consistent with Cushing’s Syndrome, should undergo a comprehensive medical evaluation. An endocrinologist will typically conduct a thorough physical examination and review medical history.
Diagnostic approaches for Cushing’s Syndrome typically involve laboratory tests to measure cortisol levels, including 24-hour urinary free cortisol, late-night salivary cortisol, and dexamethasone suppression tests. Blood tests may also measure ACTH levels, and imaging studies like CT or MRI scans of the pituitary and adrenal glands help identify underlying tumors. For evaluating seizures, a neurological examination is performed, often followed by an electroencephalogram (EEG) to record brain electrical activity. Brain imaging, such as an MRI, is also valuable for detecting structural abnormalities that might be causing seizures.
Treatment for seizures in the context of Cushing’s Syndrome primarily focuses on addressing the underlying hormonal imbalance. Managing excess cortisol is achieved through various methods, depending on the cause. If a tumor is responsible, surgical removal is often the first-line treatment, such as transsphenoidal surgery for pituitary tumors or adrenalectomy for adrenal gland tumors. Medications to lower cortisol production or block its effects may also be prescribed, sometimes as a primary treatment or to prepare for surgery. Radiation therapy may be considered if surgery is not feasible or fully effective.
While anti-epileptic drugs (ASMs) may be used to manage seizure activity directly, the ultimate goal is to alleviate symptoms by correcting the elevated cortisol. Successful treatment of Cushing’s Syndrome can lead to significant improvement or full recovery of associated symptoms, including neurological manifestations. Consulting with healthcare professionals is essential for accurate diagnosis and a personalized treatment plan for both Cushing’s Syndrome and any co-occurring seizures.