Background: The word apoplexy is defined as a sudden neurologic impairment, usually due to a vascular process. Pituitary apoplexy is characterized by sudden onset of headache, visual symptoms, altered mental status, and hormonal dysfunction due to acute hemorrhage or infarction of a pituitary gland. There is usually an existing pituitary adenoma present. The visual symptoms may include visual acuity and visual field impairment from involvement of the optic nerve or chiasm and ocular motility dysfunction from involvement of the cranial nerves traversing the cavernous sinus. Pathophysiology: This condition stems from an acute expansion of a pituitary adenoma or, less commonly, in a nonadenomatous gland, from infarction or hemorrhage. The anterior pituitary gland is perfused by its portal venous system, which passes down the hypophyseal stalk. This unusual vascular supply likely contributes to frequency of pituitary apoplexy. Some postulate that a gradual enlarging pituitary tumor becomes impacted at the diaphragmatic notch, compressing and distorting the hypophyseal stalk and its vascular supply. This deprives the anterior pituitary gland and the tumor itself of vascular supply, apoplectically causing ischemia and subsequent necrosis. Another theory stipulates that rapid expansion of the tumor outstrips its vascular supply, resulting in ischemia and necrosis. This explanation is doubtful, since most tumors that undergo apoplexy are slow growing. Frequency: Internationally: This condition results in an estimated 1.5-27.7% of cases of pituitary adenoma, although the figure is probably closer to 10%. Mohr and Hardy reviewed hospital records of 664 patients who had surgery for pituitary adenomas. They noted typical symptomatic pituitary apoplexy to occur in only 0.6% of patients with significant hemorrhagic and necrotic changes in 9.5% of surgical specimens. Frequency of intratumoral hemorrhage increases to 26%, if using only MRI criteria without clinical evidence of apoplexy. Sex: Male-to-female predominance is 2:1. Age: The age range is 37-57 years. CLINICAL Section 3 of 10 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography History: Patients may present with complaints of the following: Headache Nausea and vomiting Diplopia Changes in vision or visual field Ptosis Physical: Clinical manifestations Clinical presentation is marked by headache in 95% of cases. The headache is sudden and postulated to result from stretching and irritation of the dura mater in the walls of the sella supplied by the meningeal branches of cranial nerve V. The headache also may result from irritation of the trigeminal nerve from the expanding mass. Frequently, it is retro-orbital in location and may be unilateral at onset, then becomes generalized. Vomiting occurs in 69% of patients and often accompanies the headache. The mechanism is unclear but may be due to meningeal irritation or increased intracranial pressure. Visual acuity defects (52%) and visual field defects (64%) result from upward expansion of the tumor, which compresses the optic chiasm, optic tracts, or optic nerve. The classic visual field defect is a bitemporal superior quadrantic defect. Optic tract involvement from a prefixed chiasm is less common and results in a contralateral homonymous hemianopia. Optic nerve compression from a postfixed chiasm is rare and may mimic optic neuritis with pain on eye movement, monocular visual acuity loss, and a central scotoma on visual field testing. Ocular paresis (78%) results from compression of the cavernous sinus, which make cranial nerves III, IV, VI vulnerable to compression. If consciousness is maintained, diplopia may be present. Of the cranial nerves, the oculomotor nerve is involved most commonly, resulting in a unilateral dilated pupil, ptosis, and a globe that is deviated inferiorly and laterally. Less commonly, cranial nerve IV is involved. A fourth cranial nerve palsy typically manifests as vertical diplopia that worsens when the patient gazes in a direction opposite or tilts the head toward the direction of the hypertropic (affected) eye. It also is worsened by downgaze. The sixth cranial nerve is least commonly involved, perhaps because of its sheltered position in the cavernous sinus. Its involvement produces horizontal diplopia, which results from inability to abduct the involved eye. By virtue of its existence in the cavernous sinus, trigeminal nerve involvement may produce facial pain or sensory loss. A Horner syndrome may develop from damage to the sympathetic fibers. Hemispheric deficits may also develop. The carotid siphon may be compressed against the anterior clinoid process, leading to stroke and vasospasm from subarachnoid blood. Leakage of blood and necrotic tissue into the subarachnoid space may lead to meningismus, stupor and coma. The cerebrospinal fluid frequently is marked by increased pressure and pleocytosis (even in the absence of hemorrhage), increased numbers of red blood cells, and xanthochromia. Involvement of the hypothalamus may alter thermal regulation. Destruction of adenohypophyseal tissue may lead to endocrinologic deficiencies. Pituitary apoplexy can occur in ectopic sites. Hori examined normal adult brains at autopsy and found ectopic pituitary cells in the leptomeninges of the peri-infundibular region in 75%. He postulated that these cells may produce an ectopic pituitary adenoma. Ectopic pituitary adenomas commonly present late because they displace rather than invade vital nervous structures. They may be discovered only after the patient has pituitary apoplexy. Only one case of an ectopic pituitary adenoma that underwent apoplexy has been reported. Causes: Predisposing factors of pituitary apoplexy include endocrine stimulation tests, bromocriptine treatment, head trauma, pregnancy, and pituitary irradiation. Okuda reported one woman with a giant pituitary adenoma who underwent triple bolus stimulation test with luteinizing hormone-releasing hormone, thyrotropin-releasing hormone (THR), and insulin. The patient became stuporous, and computerized tomography (CT) scan revealed pituitary and subarachnoid hemorrhage. The investigators theorized that TRH-induced vasospasm may be a causative factor. Some associate apoplexy with administration of gonadotrophin-releasing hormone. Corticotropin-releasing hormone administration was associated with pituitary apoplexy in a patient with Cushing syndrome. In one study, bromocriptine therapy was associated with high T1 signal in the pituitary tumor on magnetic resonance imaging (MRI), but none of the patients studied had clinical evidence of pituitary apoplexy. Others associate pituitary apoplexy with long-term bromocriptine therapy. Pituitary apoplexy can occur after head trauma. This probably results from shear forces applied to the pituitary stalk with contusion, hemorrhage, and infarction of the adenoma. Apoplexy during pregnancy may be due to temporary enlargement of pituitary adenoma, which compromises blood supply. Sheehan syndrome refers to pituitary apoplexy of a nontumorous gland, presumably due to postpartum arterial spasm of arterioles supplying the anterior pituitary and its stalk. In 1937, Sheehan reported 11 cases of women who died in the puerperium, all of whom had necrosis of the anterior pituitary gland (adenohypophysis). Nine of the 11 cases had severe hemorrhage at delivery. The other 2 cases had no hemorrhage but were gravely ill prior to delivery. Usually, at least 1-2 liters of blood loss and hypovolemic shock are associated with a retained placenta. Sheehan syndrome occurs in 1-2% of women suffering significant postpartum hemorrhage. Normally, the pituitary gland hypertrophies in pregnancy. This hypertrophy combined with locally released factors mediate vascular spasm and renders the pituitary more susceptible to infarction from compromised blood flow. In Sheehan syndrome, inability to lactate after delivery due to prolactin deficiency and the development of amenorrhea from gonadotrophin deficiency classically occurs. Also, after delivery, shaved pubic hair or axillary pubic hair fails to regrow, and waxy skin depigmentation develops. Signs of hypothyroidism and hypoadrenalism may develop, and posterior pituitary (neurohypophysis) involvement with diabetes insipidus may occur. The less frequent involvement of the neurohypophysis probably stems from a difference in the anatomy of the vascular supply. The neurohypophysis contains an anastomotic ring of blood vessels that the adenohypophysis lacks. The clinical presentation of acute pituitary apoplexy has only been reported in the literature in a minority of patients with Sheehan syndrome. The more commonly reported scenario is a woman who develops amenorrhea years later, with a diagnosis of Sheehan syndrome being made retrospectively. However, Sheehan syndrome is a neurological emergency and is potentially lethal. The neuroimaging characteristics of Sheehan syndrome are distinctive. In pregnancy, the pituitary enlarges from diffuse nodular hyperplasia of prolactin secreting cells. On MRI, the normal pituitary gland is largest in the immediate postpartum period, measuring up to 11.8 mm in height and convex in appearance. The anterior pituitary is usually hyperintense on T1-weighted images in pregnant and postpartum women when compared to controls. After delivery, the size of the pituitary gland rapidly returns to normal beyond the first week postpartum. The characteristic MRI finding in Sheehan syndrome is an enlarged pituitary gland bulging under the optic chiasm with peripheral enhancement surrounding an isointense gland. Some believe that apoplexy is more prevalent in patients who produce excess pituitary hormones (eg, acromegaly, Cushing syndrome), perhaps because the tumor is fueled by the hormones. Others report that most pituitary tumors that undergo apoplexy are endocrinologically silent. Weisberg warns that radiotherapy is potentially hazardous in pituitary tumors with prior hemorrhagic, necrotic, or cystic changes. Apoplexy may be precipitated in these cases.