What are the primary causes of pituitary apoplexy?

Causes of Pituitary Apoplexy

Pituitary apoplexy is primarily caused by spontaneous hemorrhage or infarction of a pre-existing pituitary adenoma (pituitary neuroendocrine tumor), though it can also occur in previously normal glands under specific precipitating conditions. 1, 2

Primary Underlying Pathology

The main cause is hemorrhagic or vascular impairment of a pituitary adenoma, which accounts for the majority of cases. 1, 2 The sudden hemorrhage or infarction leads to acute expansion of sellar contents, compressing surrounding structures and portal vessels, resulting in the characteristic clinical syndrome. 3

Precipitating Factors

While many cases occur spontaneously, precipitating factors are present in up to 30% of cases. 2 The American College of Radiology identifies the following clinical settings where pituitary hemorrhage commonly occurs:

Tumor-Related Factors

• Initial manifestation of an undiagnosed adenoma - apoplexy can be the first presentation of a pituitary tumor 1
• Treated adenoma - hemorrhage in previously diagnosed and treated tumors 1
• Prior radiation treatment to the pituitary region 1

Medication-Related Factors

• Anticoagulation therapy increases hemorrhage risk 1
• Gonadotropin-releasing hormone (GnRH) agonist therapy - exceedingly rare but documented, with proposed mechanisms including sudden cell shrinkage and metabolic hyperactivity within the pituitary gland 4

Physiologic States

• Pregnancy and immediate postpartum period - PA may develop during these high-risk periods 1, 2

Traumatic Causes

• Trauma to the head can precipitate hemorrhage 1
• Stalk transection or post-operative sella changes 1

Rare Causes in Normal Glands

While less common, pituitary apoplexy can develop in healthy pituitary glands affected by:

• Inflammation
• Infection
• Other pathologic processes 2

Clinical Caveat

Not all cases of intrapituitary hemorrhage (such as subacute/necrotic adenoma) are associated with symptomatic pituitary apoplexy, so caution is needed when interpreting pituitary hemorrhage findings in the context of clinical symptoms. 1 The diagnosis requires correlation between imaging findings and the acute clinical syndrome of sudden headache, visual disturbances, hormonal dysfunction, and potential neurological compromise.