Pituitary Apoplexy Clinical Presentation

Patients with pituitary apoplexy may present with the following complaints ^[7] :

• Headache (often sudden and severe)
• Nausea and vomiting
• Diplopia
• Changes in vision or visual field
• Ptosis

There is one case report of recalcitrant hiccups in association with pituitary apoplexy. ^[8]

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. 

Automated visual field showing a bitemporal field defect due to compression of the optic chiasm from below.

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Ocular paresis (78%) results from compression of the cavernous sinus, which makes cranial nerves III, IV, and VI vulnerable to compression. If consciousness is maintained, diplopia may be present. Of the cranial nerves, the oculomotor nerve (cranial nerve III) is involved most commonly, resulting in a unilateral dilated pupil, ptosis, and a globe that is deviated inferiorly and laterally. ^[9]

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.

Cranial nerve VI is least commonly involved, perhaps because, in the cavernous sinus, it is more sheltered from the pituitary expansion than are cranial nerves III and IV. Abducens involvement produces horizontal diplopia owing to the inability to abduct the involved eye.

Trigeminal nerve (cranial nerve V) involvement may produce facial pain or sensory loss.

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.

Rarely, 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%. ^[10] 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.

Predisposing factors of pituitary apoplexy include endocrine stimulation tests, bromocriptine treatment, head trauma, pregnancy, pituitary irradiation, and, perhaps, anticoagulation. ^[11]

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. ^[12] The patient became stuporous, and computerized tomography (CT) scan revealed pituitary and subarachnoid hemorrhage (SAH). 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.

Pituitary apoplexy during induction chemotherapy for acute myeloid leukemia has been reported by Silberstein and colleagues. ^[13]

Apoplexy has been reported after cardiac bypass surgery by Thurtell and colleagues. ^[14]

Brar and Garg reported a case of pituitary apoplexy in a young man who ascended to high altitude gradually, even after proper acclimatization. ^[15]

Pituitary apoplexy has been reported in a patient with dengue fever and thrombocytopenia. ^[16] Kruljac et al reported a patient with pituitary metastasis presenting as ischemic pituitary apoplexy after heparin-induced thrombocytopenia. ^[17]

Apoplexy may occur during pregnancy. Normally, the pituitary gland hypertrophies in pregnancy because of diffuse nodular hyperplasia of the prolactin secreting cells. This hypertrophy, combined with locally released factors, mediates vascular spasm and renders the pituitary more susceptible to infarction from compromised blood flow.

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.

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. Notwithstanding, Sheehan syndrome is regarded as a neurologic emergency and is potentially lethal.

In Sheehan syndrome, lactation failure may occur as a result of prolactin deficiency, and there may be amenorrhea due to gonadotrophin deficiency. In addition, in the postpartum period, shaved pubic or axillary 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 neuroimaging characteristics of Sheehan syndrome are distinctive. 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 with 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; this characteristic MRI finding is called the "pituitary ring sign" (see Imaging Studies). ^[18]

Weisberg warns that radiotherapy is potentially hazardous in pituitary tumors with prior hemorrhagic, necrotic, or cystic changes. ^[19] Apoplexy may be precipitated in these cases.

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.

Ahmed and Semple reviewed the potential complications of pituitary apoplexy, one being mechanical occlusion of the internal carotid arteries in the cavernous sinus, and the other being vasospasm. ^[20] Both may result in brain ischemia.

Complications include optic neuritis, acute ophthalmoplegia, increased intracranial pressure, extraocular muscle paralysis, and ptosis.

Frontal lobe herniation and chiasmal herniation have been reported. ^[21]