Can Adrenal Insufficiency Cause Seizures?
Yes, adrenal insufficiency can cause seizures, particularly during adrenal crisis when impaired consciousness manifests as seizures, or through severe hyponatremia and hypoglycemia that lower the seizure threshold.
Mechanism and Clinical Context
Seizures occur in adrenal insufficiency through several pathophysiological pathways:
Direct Crisis Manifestation
According to the 2024 European Society of Endocrinology/Endocrine Society joint guidelines, seizures are explicitly listed as a manifestation of impaired consciousness during adrenal crisis 1. The diagnostic criteria for adrenal crisis include hypotension or hypovolemic shock plus impaired consciousness, which encompasses "lethargy, confusion, somnolence, collapse, delirium, coma, and seizures" 1.
Metabolic Derangements
The seizures result from:
- Severe hyponatremia - a common electrolyte disturbance in adrenal insufficiency that directly lowers seizure threshold
- Hypoglycemia - cortisol deficiency impairs gluconeogenesis
- Cerebral hypoperfusion - from the profound hypotension and shock characteristic of adrenal crisis
Clinical Evidence
Recent case reports demonstrate this association clearly:
- A 2025 case described a 68-year-old woman with hypopituitarism who developed new-onset seizures after abruptly discontinuing chronic steroid therapy, with seizures resolving after hydrocortisone replacement 2
- Another 2025 case reported central-variant posterior reversible encephalopathy syndrome (PRES) with seizures precipitated by adrenal insufficiency, attributed to labile blood pressure causing rapid alterations in cerebral perfusion pressure 3
High-Risk Scenarios
Be particularly vigilant for seizures in these contexts 1:
Glucocorticoid-Related
- Abrupt glucocorticoid withdrawal after long-term treatment
- Tapering below physiological replacement doses (equivalent to <15-25 mg hydrocortisone daily)
- Recent cessation of any glucocorticoid formulation (oral, inhaled, topical, intra-articular)
Stress/Illness Triggers
- Acute infections (gastrointestinal, respiratory, genitourinary, sepsis)
- Physical trauma or surgery
- Severe psychological stress
Drug Interactions
- Initiation of strong CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital, rifampicin) which accelerate glucocorticoid metabolism 1
Diagnostic Approach
When seizures occur with suspected adrenal insufficiency, look for:
Classic biochemical findings:
- Low morning cortisol (<5 µg/dL in primary AI; 5-10 µg/dL in secondary AI) 4
- Hyponatremia (though absence does not exclude the diagnosis - the 2025 case report emphasizes seizures can occur without classic electrolyte abnormalities) 2
- Hypoglycemia
- Hyperkalemia (in primary adrenal insufficiency only)
Clinical presentation:
- Hypotension or shock out of proportion to illness severity
- Nausea, vomiting, severe fatigue
- History of glucocorticoid use or known adrenal insufficiency 1
Critical Management Points
If adrenal crisis with seizures is suspected, immediately administer 100 mg hydrocortisone IV or IM followed by rapid volume resuscitation with 0.9% saline 1. This should be done even before confirmatory testing, as the guidelines explicitly state that "short-term administration of parenteral glucocorticoids at the recommended doses is safe; hence, treatment should be initiated even if an adrenal crisis diagnosis is eventually ruled out" 1.
Common Pitfall
Do not delay treatment waiting for:
- Cortisol levels to return
- Classic electrolyte abnormalities to appear
- Neuroimaging to exclude other causes
The shock in adrenal crisis is typically resistant to inotropes and fluid resuscitation alone if glucocorticoids are not given 1.
Long-Term Seizure Management
For patients with confirmed adrenal insufficiency who experienced seizures:
- Continue physiological glucocorticoid replacement (hydrocortisone 15-25 mg daily or prednisone 3-5 mg daily) 4
- Add fludrocortisone 0.05-0.3 mg daily if primary adrenal insufficiency 4
- Consider anti-epileptic prophylaxis (levetiracetam was used successfully in recent cases) 2, 3
- Educate on stress dosing and provide emergency injectable hydrocortisone 4
The seizures typically resolve with adequate glucocorticoid replacement and do not recur if adrenal insufficiency is properly managed 2, 3.