In a 24-year-old woman with uterine fibroids and menorrhagia who received a leuprolide injection and developed headache, vomiting, and seizures the next day, what is the most likely cause?

Pseudotumor Cerebri (Idiopathic Intracranial Hypertension) Secondary to Leuprolide Acetate

The most likely cause of this patient's headache, vomiting, and seizures is pseudotumor cerebri (idiopathic intracranial hypertension) induced by leuprolide acetate. This is a rare but well-documented complication of GnRH agonist therapy that requires immediate recognition and management.

Clinical Reasoning

While leuprolide acetate is commonly associated with hypoestrogenic effects including headaches 1, the acute presentation of severe headache, vomiting, and seizures within 24 hours points to a more serious neurological complication rather than typical medication side effects.

The evidence strongly supports pseudotumor cerebri as the diagnosis:

• Case reports document pseudotumor cerebri occurring after leuprolide acetate administration, with patients presenting with headache, nausea, vomiting, and visual disturbances 2, 3
• One case specifically describes a 6.5-year-old who developed pseudotumor cerebri after just 2 doses of leuprolide acetate 3.75 mg, presenting with headache, nausea, and vomiting 2
• Another case documented unilateral papilloedema and visual field defects in a 35-year-old woman on leuprolide, with complete recovery after drug discontinuation 3
• The mechanism appears related to leuprolide strongly inducing increased cerebrospinal fluid pressure 3

Immediate Management Steps

Perform fundoscopy immediately to look for papilloedema with blurred disc margins, which is the hallmark finding 2. This is critical because:

• Papilloedema confirms elevated intracranial pressure
• Permanent vision loss can occur if untreated
• The diagnosis can be made clinically without waiting for imaging

Obtain urgent neuroimaging (CT or MRI brain) to exclude:

• Space-occupying lesions
• Venous sinus thrombosis
• Other structural causes of increased intracranial pressure

Measure opening pressure with lumbar puncture if imaging is normal, which will show elevated CSF pressure (>250 mm H₂O) with otherwise normal CSF composition 3.

Treatment Algorithm

1. Discontinue leuprolide acetate immediately - this is the most critical intervention 2, 3

2. Initiate acetazolamide (typically 500-1000 mg daily in divided doses) to reduce CSF production 2

3. Manage seizures with appropriate anticonvulsants if they persist

4. Monitor visual function closely with:

   • Serial fundoscopy
   • Visual field testing
   • Visual acuity measurements

5. Continue treatment for 6-8 weeks - one case showed complete resolution of papilloedema after 6 weeks of acetazolamide with drug withdrawal 2

Critical Pitfalls to Avoid

• Do not attribute symptoms to "typical GnRH agonist side effects" when seizures are present - this indicates serious pathology
• Do not delay fundoscopy - this is the key diagnostic test and can be performed immediately at bedside
• Do not restart leuprolide - the condition is directly related to the medication 3
• Do not ignore visual complaints - permanent vision loss can occur without prompt treatment

Alternative Fibroid Management

Given this serious adverse event, consider alternative approaches for this patient's fibroids 1:

First-line alternatives:

• Combined oral contraceptives or levonorgestrel-IUD for bleeding control
• Tranexamic acid (non-hormonal option)

Second-line alternatives if GnRH suppression still needed:

• Oral GnRH antagonists (elagolix, relugolix) with add-back estrogen/progestin therapy may have different safety profile
• However, given this severe reaction, avoiding all GnRH-modulating agents may be prudent

Definitive options:

• Uterine artery embolization
• Myomectomy (hysteroscopic, laparoscopic, or open depending on fibroid characteristics)

The prognosis for pseudotumor cerebri secondary to leuprolide is generally excellent with prompt recognition and drug discontinuation, with complete resolution expected within weeks to months 2, 3.