Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension

Benign intracranial hypertension has an incidence of 1 per 100 000 children.3 As “benign” belies the potentially debilitating nature of this disorder, including the risk of irreversible blindness,4 the synonyms “pseudotumor cerebri” and “idiopathic intracranial hypertension” are sometimes preferred. Although the pathophysiological basis has not been determined, benign intracranial hypertension has been associated with vitamin deficiencies and toxicities, obesity, head injury,5 adrenal insufficiency,6 and medications, including topical and systemic steroids.7-9 To the best of our knowledge, this is the first reported association between benign intracranial hypertension and inhaled corticosteroids (we conducted a MEDLINE search, using multiple search terms, of English language publications from 1966 to June 2005).

The diagnosis of benign intracranial hypertension in our case was based on modified Dandy’s criteria, an elevated cerebrospinal fluid (CSF) opening pressure (using the paediatric reference range),1,2 and repeated instances of immediate headache relief with lumbar puncture. The ophthalmological findings were non-specific but supported the diagnosis. Magnetic resonance venography would have excluded venous sinus thrombosis (an important cause of benign intracranial hypertension), but there was no reason to suspect a hypercoagulable tendency.

As the CSF opening pressure was first measured 2 months after the patient sustained a minor head injury, we cannot determine whether this injury was the trigger for benign intracranial hypertension or incidental to it. However, the injury alone cannot explain the benign intracranial hypertension in this patient, given its mild nature and the absence of any radiological evidence of parenchymal brain injury.

The adrenal suppression was most likely secondary to inhaled corticosteroid therapy. This is supported by the gradual adrenal recovery after withdrawal of inhaled corticosteroids. The past history of collapse suggests the onset of the adrenal suppression may have occurred 1 year before presentation.

Given the absence of papilloedema at presentation, and the fact that the headache and elevated CSF opening pressure were clearly temporally associated with the withdrawal of inhaled corticosteroids, we suggest that the benign intracranial hypertension was related to the withdrawal of the steroid dose. Benign intracranial hypertension has previously only been reported in cases of primary adrenal insufficiency (Addison disease),6 or in association with the use or withdrawal of topical, oral or intranasal corticosteroids.7-9

Clinicians should be mindful of benign intracranial hypertension as a potential side effect when prescribing inhaled corticosteroids. Our case emphasises the importance of using appropriate inhaled corticosteroid dosage and “back titration”. Patients receiving inhaled corticosteroids require regular review. Dosages should be monitored to achieve the minimal dose for symptom control.10

Temporal association between headache severity, cortisol levels, and cerebrospinal fluid opening pressure

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Medication: F = fluticasone propionate (initially 1000 μg/day); A = acetazolamide (initially 1000 mg/day). CSF = cerebrospinal fluid.