Low Free T3 and Its Relationship to Non-Epileptic Seizures
Low free T3 (triiodothyronine) levels can potentially contribute to non-epileptic seizures, and treatment should focus on addressing the underlying thyroid dysfunction while monitoring for seizure activity.
Relationship Between Low Free T3 and Non-Epileptic Seizures
Thyroid Dysfunction and Seizure Risk
- Low free T3 can occur in various clinical contexts, including primary hypothyroidism, central hypothyroidism, or as part of non-thyroidal illness syndrome (NTIS) 1
- Thyroid hormone abnormalities, including low T3, have been associated with an increased threshold for seizures 2
- Patients with 22q11.2 deletion syndrome demonstrate a clear connection between thyroid dysfunction and seizure activity, with seizures being common across the lifespan 2
Mechanisms of Seizure Induction
- Low free T3 may affect neuronal excitability through:
- Altered neurotransmitter function
- Changes in cerebral metabolism
- Electrolyte disturbances (particularly when associated with hypocalcemia)
- Hypocalcemia, which can accompany thyroid dysfunction, is a significant trigger for seizures 2
Diagnostic Approach
Initial Evaluation
- Confirm the non-epileptic nature of seizures through:
- Electroencephalography (EEG)
- Brain imaging (CT/MRI) to rule out structural causes
- Detailed seizure semiology assessment
Thyroid Function Assessment
- Complete thyroid panel including:
- TSH, free T4, free T3
- Thyroid antibodies to determine etiology
- Repeat testing to confirm abnormal values, as a single abnormal value is insufficient for diagnosis 3
Associated Conditions to Evaluate
- Check calcium, magnesium, and parathyroid hormone levels, as hypocalcemia can trigger seizures 2
- Assess for other endocrine abnormalities, particularly in patients with suspected central hypothyroidism 3
- Consider medication effects, as certain antiepileptic drugs can alter thyroid function 4
Treatment Approach
Thyroid Hormone Replacement
- For confirmed hypothyroidism with low free T3:
Monitoring and Adjustment
- Monitor thyroid function every 4-6 weeks initially until stable, then every 6-12 months 3
- If both adrenal insufficiency and hypothyroidism are present, ALWAYS start steroids prior to thyroid hormone to avoid adrenal crisis 3
- Be cautious with levothyroxine treatment in patients with a history of seizures, as inappropriate treatment may potentially trigger seizures 5
Management of Seizures
- For non-epileptic seizures related to hypocalcemia:
- For seizures not related to electrolyte abnormalities:
Special Considerations
Non-Thyroidal Illness Syndrome (NTIS)
- Low T3 may represent NTIS in acutely ill patients rather than true hypothyroidism 1
- Treatment of NTIS remains controversial and generally not recommended unless true hypothyroidism is confirmed 1
Medication Effects
- Antiepileptic drugs (especially carbamazepine, phenobarbital, and valproate) can lower thyroid hormone levels 6, 4
- Combination therapy with multiple antiepileptic drugs may have more pronounced effects on thyroid function 4
Monitoring During Critical Illness
- During acute illness, monitor thyroid function carefully as changes may reflect NTIS rather than primary thyroid disease 1
- A falling TSH with normal or lowered T4 may suggest pituitary dysfunction; check cortisol levels in these cases 2
Clinical Pitfalls to Avoid
- Misdiagnosing transient TSH elevation following seizures as subclinical hypothyroidism 5
- Initiating thyroid hormone replacement without confirming persistent thyroid dysfunction 5
- Failing to check calcium and magnesium levels in patients with seizures and thyroid dysfunction 2
- Overlooking the potential effects of antiepileptic medications on thyroid function 6, 4
By addressing the underlying thyroid dysfunction while carefully monitoring for seizure activity, most patients with non-epileptic seizures related to low free T3 can achieve significant improvement in their condition.