Association Between Empty Sella Syndrome and Migraine
Empty sella syndrome (ESS) is frequently associated with headache as a presenting symptom, but the headaches are typically nonspecific in character rather than true migraine, and management should focus on evaluating for pituitary dysfunction and treating headache symptoms according to standard migraine protocols.
Understanding the Relationship
Headache Prevalence in ESS
Headache is one of the most commonly reported symptoms in patients with empty sella, occurring in 62% of cases 1. The headaches are typically:
- Daily and continuous in nature
- Anteriorly or retrobulbar located (frontal or behind the eyes)
- Nonspecific in character 2
- More common in middle-aged, overweight women 2
The relationship between ESS and headache remains somewhat controversial regarding causation 3. Some evidence suggests that increased intracranial pressure (ICP) may play a pathogenic role, as elevated CSF pressure was documented in 35 of 62 patients (56%) who underwent lumbar puncture 1, and impaired ICP/CSF dynamics was observed in 76.8% of patients in a larger series 4.
Key Clinical Distinction
The headaches associated with ESS are not typically classic migraine but rather represent a distinct headache pattern potentially related to:
- Stretching of the sellar floor dura 5
- Increased intracranial pressure 4, 1
- Associated endocrine dysfunction
Evaluation Algorithm for ESS Patients with Headache
Step 1: Confirm ESS Diagnosis
- MRI with dedicated pituitary sequences to visualize CSF herniation into sella turcica
Step 2: Screen for Pituitary Dysfunction
This is critical as 40.5% of primary empty sella patients have at least one hormonal axis deficiency, with 29% of incidentally diagnosed cases affected 6. Test:
- Cortisol (hypoadrenalism in 13.5-17.7%)
- Thyroid function (hypothyroidism in 2.8-29.2%)
- Gonadal hormones (hypogonadism in 8.5-50.4%)
- Prolactin (hyperprolactinemia in 2.9-15.7%)
- Growth hormone/IGF-1 (deficiency in 12.5-20.4%)
Risk factors for hypopituitarism include male sex, total vs. partial empty sella, and traumatic brain injury 6.
Step 3: Evaluate for Increased ICP
Consider lumbar puncture with opening pressure measurement if patient has:
- Severe, intractable headache
- Visual disturbances
- Signs of papilledema on ophthalmologic exam 7
Step 4: Ophthalmologic Assessment
Formal ophthalmology referral to evaluate for:
- Papilledema
- Visual field defects (quadrantanopsia can occur)
- Optic nerve compression 7
Management Approach
Treat Identified Hormonal Deficiencies
Replace deficient hormones according to standard endocrine protocols. This may improve headache symptoms indirectly 8.
Headache Management
For standard migraine treatment in ESS patients, follow evidence-based migraine protocols 9:
Acute Treatment:
- CGRP antagonists (gepants) show robust efficacy with NNT of 13 for pain freedom at 2 hours
- Triptans remain effective for acute migraine
- Greater occipital nerve blockade can be considered (weak recommendation) - easily performed in outpatient settings with favorable safety profile 9
Preventive Treatment (if ≥4 migraine days/month):
- CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) have strong evidence for both episodic and chronic migraine prevention 9
- Note: Monitor blood pressure with erenumab due to postmarketing hypertension risk 9
Surgical Intervention for Intractable Headache
Consider neurosurgical referral if:
- Severe intracranial hypertension documented on lumbar puncture
- Intractable headache unresponsive to medical management
- CSF rhinorrhea present
Surgical options include:
- CSF shunt placement - effective in 35 of 36 patients with severe intracranial hypertension 4
- Transsphenoidal repair of sellar floor - can provide complete headache relief in select cases 5
Important Clinical Pitfalls
- Don't assume all headaches in ESS are benign - Screen for increased ICP and visual compromise
- Don't overlook endocrine testing - Even asymptomatic patients have high rates of hormonal dysfunction that may worsen over time 10
- Obesity is a significant risk factor - Higher BMI correlates with gonadal insufficiency and may exacerbate pituitary dysfunction 10
- Monitor for progression - Partial empty sella can progress to total empty sella with hormonal deterioration 6
- Women are disproportionately affected - 12:1 female predominance in some series, with higher rates of gonadal dysfunction 2, 10
The prognosis for ESS patients is generally good, with most never developing significant symptoms 7. However, the combination of headache with ESS warrants thorough endocrine and neuro-ophthalmologic evaluation rather than dismissing it as incidental.