AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The word apoplexy is defined as a sudden neurologic impairment, usually due to a vascular process. Pituitary apoplexy is characterized by a sudden onset of headache, visual symptoms, altered mental status, and hormonal dysfunction due to acute hemorrhage or infarction of a pituitary gland. An existing pituitary adenoma is usually present. The visual symptoms may include both visual acuity impairment 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

International

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.¹⁷ 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

The male-to-female predominance is 2:1.

Age

The age range is 37-57 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients may present with the following complaints:

• Headache
• Nausea and vomiting
• Diplopia
• Changes in vision or visual field
• Ptosis

Physical

• 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 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.
  
  
  • 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, the 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.
• 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.

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.²⁰ 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 the 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, mediates 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 occurs and amenorrhea due to gonadotrophin deficiency classically develops.
    • 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.
  • Weisberg warns that radiotherapy is potentially hazardous in pituitary tumors with prior hemorrhagic, necrotic, or cystic changes.²⁹ 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Aneurysmal rupture
Acute ophthalmoplegia

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Evaluate electrolytes, glucose, and pituitary hormones.

Imaging Studies

• CT scan and MRI are radiologic tests used to evaluate the pituitary.
• • MRI is the most sensitive imaging study for evaluating the pituitary gland, possibly visualizing hemorrhage not seen on CT scan.
  • In the first 3-5 days, hemorrhage within the sella is isointense or hypointense on T1-weighted images. On T2-weighted sequences, the blood appears hypointense.

Histologic Findings

Histologically, many of these tumors display hemorrhagic necrosis in their substance. This has been postulated to result from unrecognized episodes of focal hemorrhage. Bills reviewed histories of 37 patients with symptomatic pituitary apoplexy.² By immunostaining criteria, null-cell adenomas were the most frequent tumor type found.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment consists of the following:

• Medically stabilize the patient.
• Administer high-dose corticosteroids (most patients have hypopituitarism).
• Immediately evaluate electrolytes, glucose, and pituitary hormones.
• Administer appropriate endocrinologic replacement therapy alone or combined with transsphenoidal surgical decompression of the tumor.

Surgical Care

Evacuation of the tumor by a neurosurgeon should be planned once the patient is medically stable.

Consultations

• Neurosurgery for potential surgical therapy
• Medicine for general medical management
• Endocrinology for hormonal management

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to correct the corticosteroid deficiency, to reduce morbidity, and to prevent complications.

Drug Category: Corticosteroids

Replenish the cortisol that would normally be produced under this type of physiologic stressful situation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Monitor metabolic status, visual acuity, and visual fields.

Complications

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

Prognosis

• Pituitary apoplexy can be a life-threatening condition, which is not easily diagnosed or treated.

Patient Education

• Educate patients about the disorder and the complications that can arise from the treatment of the disorder.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Pituitary apoplexy is difficult to diagnose, and care should be taken to fully examine patients with subtle symptoms that include headache and both visual field loss and visual acuity loss.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jun 26, 2007