Etiology of Pituitary Apoplexy
Pituitary apoplexy is primarily caused by spontaneous hemorrhage or infarction of a pre-existing pituitary adenoma, though it can rarely occur in previously normal pituitary glands affected by inflammation or infection. 1, 2
Primary Underlying Pathology
The overwhelming majority of pituitary apoplexy cases result from hemorrhagic or vascular impairment of a pituitary adenoma (pituitary neuroendocrine tumor). 1, 2 This represents the main etiologic mechanism, with most patients harboring previously undiagnosed clinically non-functioning adenomas at the time of apoplexy. 3, 4
Null-cell adenomas are the most common tumor type underlying apoplexy, accounting for 61% of cases in surgical series. 4 Non-functioning pituitary adenomas represent the predominant substrate, with many patients completely unaware of the adenoma's existence prior to the acute apoplectic event. 5, 3
Precipitating Factors
While apoplexy often occurs spontaneously, identifiable precipitating factors are present in up to 30% of cases. 2 The American College of Radiology identifies several key triggers:
Iatrogenic and treatment-related factors:
- Prior radiation treatment to the pituitary region 1
- Anticoagulation therapy, which increases hemorrhage risk 1
- Major surgery 3
- GnRH agonist therapy (exceedingly rare, with fewer than 30 reported cases) 6
- Post-operative sella changes or stalk transection 1
Medical conditions:
- Arterial hypertension (present in 26% of apoplexy patients) 3, 4
- Head trauma 1
- Infection (can contribute even in healthy pituitary glands) 1
Physiologic states:
- Pregnancy and immediate postpartum period 2
Age and Gender Distribution
Pituitary apoplexy occurs most frequently in men aged 50-60 years (mean age 49.8 years), with a male predominance in most adult series. 2, 3, 4 However, apoplexy is rare in children and adolescents, though when it does occur in this population, it is probably more common than in adults with non-functioning adenomas and may be more severe. 7, 8
Special Populations
In children and young people (CYP), pituitary apoplexy represents a distinct presentation pattern. 7 Arginine vasopressin deficiency (central diabetes insipidus) is extremely infrequent at diagnosis of non-functioning pituitary adenomas unless the tumor has undergone apoplexy, and its presence should prompt consideration of alternative diagnoses such as craniopharyngioma, histiocytosis, or germ-cell tumor. 7
Clinical Correlation Caveat
Not all cases of intrapituitary hemorrhage detected on imaging represent symptomatic pituitary apoplexy. 1 The diagnosis requires correlation between imaging findings showing hemorrhage and the acute clinical syndrome of sudden headache, visual disturbances, and endocrine dysfunction. 1, 5 Subclinical hemorrhage discovered incidentally at surgery should be distinguished from classical pituitary apoplexy, which presents as a medical emergency. 4