Case Presentation

A 43-year-old white man presented to the emergency department with a 2-day history of worsening headache accompanied by severe bilateral vision loss. He described the headache as "the worst of his life." He complained of rapidly progressing vision loss that was more severe in his left eye. The patient denied any nausea, vomiting, fever, chills, chest pain, abdominal pain, back pain, or other focal neurologic deficits. His blood pressure (BP) was 135/99 mm Hg and his heart rate, 90 beats/min.

The patient's medical history included chronic sinusitis, viral cardiomyopathy, and depression. His daily medications were carvedilol (Coreg), amlodipine (Amvaz, Norvasc), fosinopril sodium (Monopril), atorvastatin (Lipitor), escitalopram (Lexapro), ketorolac tromethamine, and hydrocodone (eg, Lortab, Panacet, Vicodin). Surgical history included a remote cleft palate repair and back surgery. The family history was notable for macular degeneration and glaucoma.

Ophthalmic examination revealed a visual acuity of 20/200 in the right eye and 20/400 in the left eye. The pupils were sluggishly responsive to light. Bedside visual field testing by confrontation (ie, face to face) revealed a bitemporal hemianopsia, along with a complete loss of the inferior fields. Mild proptosis and conjunctival injection were evident bilaterally. The remainder of the examination was unremarkable.

Magnetic resonance imaging (MRI) of the brain showed a large pituitary macroadenoma (Figure 1), with previous hemorrhage consistent with pituitary apoplexy. The predominantly sellar mass extended into the sphenoid sinus and third ventricle and compressed the left lateral ventricle. Substantial compression of the optic nerve was noted.

Laboratory tests revealed: fasting cortisol, 858 μg/dL (normal, 7-25 μg/dL); adrenocorticotropic hormone (ACTH), 812 pg/mL (normal, 10-60 pg/mL); prolactin, 0.5 ng/mL (normal, 1.6-18.8 μg/mL); insulinlike growth factor-1, 196 ng/mL (normal, 90-360 ng/mL). Comprehensive endocrine-related laboratory testing was not done in the acute setting.

The patient underwent transsphenoidal hypophysectomy one day after presentation. Pathologic evaluation revealed an ACTH-positive pituitary adenoma. Two weeks after surgery, repeat MRI demonstrated that the compression on the optic chiasm had been released (Figure 2). The patient's anticipated postsurgical panhypopituitarism was treated with hormonal supplementation.

Figure 1—Preoperative MRI showing displacement of the optic chiasm by a large pituitary macroadenoma (arrow), with previous hemorrhage.	Figure 2—Postoperative MRI after resection of the pituitary macroadenoma (arrow); the optic chiasm is no longer displaced.

Discussion

Pituitary apoplexy is marked by a rapid enlargement of the pituitary gland secondary to hemorrhage or infarction.^1-4 Classic clinical features in the acute setting include severe headache, visual field disturbances, ophthalmoplegia, decreased visual acuity, altered consciousness, nausea and/or vomiting, and hypopituitarism.^4-6 These signs and symptoms are thought to be related to a mass effect of the rapidly evolving hemorrhage. Patients usually show a rapid response to treatment. Because pituitary apoplexy may precipitate a hypotensive state as a result of acute cortisol deficiency, timely diagnosis is critical.

Pituitary apoplexy is most often found in middle-aged men, slightly less often in women, and rarely in children.^1,7,8 Although typically occurring in patients with pituitary macroadenomas, pituitary apoplexy can also be seen in individuals with no history of pituitary pathology. In one study, 81% of patients presenting with pituitary apoplexy had no history of pituitary tumor, as well as no history of endocrine dysfunction.⁷ Pituitary apoplexy can also occur in association with craniopharyngiomas, lymphocytic hypophysitis, and in patients with a normal pituitary gland.⁷

Although the exact precipitants of pituitary apoplexy remain speculative, 4 general categories that may contribute to this phenomenon have been hypothesized⁹:

1. Reduced blood flow in the pituitary gland from BP fluctuation, such as in the setting of cardiac surgery, hemodialysis, or hypoperfusion caused by increased intracranial pressure.
2. Degenerative changes in the pituitary gland microvasculature, as in diabetes or in chronic hypertension.
3. Stimulation of the pituitary gland from high-level estrogen states, including pregnancy or exogenous estrogen administration, or in response to excessive steroid production from surgery-related stressors.
4. Anticoagulated state associated with the use of anticoagulant medications or thrombolytics, or related to thrombocytopenia.

Because pituitary apoplexy often occurs without any precipitating factors or an associated disease, however, the absence of such factors should not diminish one's clinical suspicion when evaluating a patient with acute headache, especially in the context of neuroophthalmologic symptoms.

The clinical manifestations of pituitary apoplexy can vary significantly. Between 87% and 92% of patients present with a headache, and up to 50% have visual deficits.^6,7 However, even though visual field defects and cranial nerve abnormalities are not always present, the rapidly evolving nature of pituitary apoplexy, particularly early in its course, can produce a spectrum of visual field changes. The variety of these changes, if unanticipated, may pose a significant diagnostic challenge before completion of appropriate imaging studies. For example, our patient presented with bitemporal hemianopsia, along with binasal inferior quadranopsia.

One would usually expect pituitary-associated or other infrachiasmatic lesions to exert chiasmatic compression from below, producing more predominant deficits in the superior visual field. Because pituitary apoplexy is typified by rapidly evolving hemorrhage, however, the classical presentations may not apply. We hypothesized that in our patient the macroadenoma, although technically infrachiasmatic, exerted an expansive pressure from below, substantial enough to produce a suprachiasmatic-like visual defect because the optic chiasm was pressed against the sphenoid.

Differential diagnosis
The differential diagnosis of acute-onset severe headache with vision changes is broad and contributes to the daunting task of correctly identifying pituitary apoplexy. Overlapping features of several serious and potentially fatal conditions underscore the importance of making the correct diagnosis. Clinical features are shared by medical entities such as subarachnoid hemorrhage, migraine headache, optic neuritis, stroke, myocardial infarction, encephalitis, sinusitis, pituitary abscess, cavernous sinus thrombosis, meningitis, and craniopharyngioma.⁷

Imaging studies
Considering the wide variability in the clinical presentation of pituitary apoplexy, MRI can often identify associated areas of infarction, hemorrhage, and chiasmatic compression.^1,5,10 MRI has shown a sensitivity between 88% and 91% for detecting pituitary lesions.^4,11 Computed tomography (CT), however, does not appear to be as reliable. Studies suggest that a CT scan can identify associated pituitary hemorrhage in only 21% to 46% of pituitary apoplexy cases.^1,4 In a study of 45 patients, pituitary apoplexy was correctly identified in only 28% of cases by CT scanning compared with 91% of cases by MRI.¹¹ In another study of 35 patients, MRI identified pituitary hemorrhage in 88% of the patients compared with 21% with CT.⁴

In describing his headache as the worst of his life, our patient used a phrase that raises concern for the possibility of subarachnoid hemorrhage, a condition that is usually investigated with the use of CT.¹² Therefore, because CT scanning exhibits only a modicum of success in demonstrating pituitary hemorrhage, when clinical suspicion for pituitary apoplexy is high, MRI is an important next step.

Figure 3—Results of visual field testing in (A) left eye and in (B) right eye 2 months postoperatively. Darker areas (arrows) correspond to areas of vision loss.

Figure 4—Improvements in both eyes in peripheral vision 4 months postoperatively.

Figure 5—Continued improvement at 1 year postoperatively.

Cortisol deficiency
In our patient, acute cortisol deficiency was not evident by laboratory testing or by clinical signs or symptoms; rather, laboratory results revealed cortisol excess from the pituitary adenoma. As with clinical presentation, laboratory data can vary widely in pituitary apoplexy. In a study of 62 patients, hypopituitarism (secondary to crush injury from hemorrhage) was detected in 73% of the cases, normal function in 24%, and pituitary hyperfunction in only 3% of the patients.⁷ Our case, therefore, represents the rarer subset of patients with pituitary apoplexy who present with increased cortisol levels.

Treatment
Transsphenoidal decompression, in combination with corticosteroid replacement therapy, constitutes the primary treatment for pituitary apoplexy. Several studies support early surgical intervention, based on the ability of surgery to reverse the neuroophthalmologic deficits, improve visual acuity, lower the incidence of hypopituitarism, and reduce mortality.^1,4,6,13 However, other evidence supports a conservative approach. One study of 11 patients showed that conservative treatment (steroid therapy alone) was as effective as surgical intervention for patients presenting with ophthalmoplegia but without other visual deficits or diminished consciousness.¹⁴ A retrospective review of 30 patients showed no differences in outcome among patients managed surgically or conservatively, regardless of initial presentation.¹⁵

The diminished level of consciousness, hypothalamic disturbance, or visual impairment may constitute reasons for emergency surgical intervention.⁷ Although the same investigators advocate early surgery in patients with ophthalmoplegia, they nonetheless note that conservative management may also be justified, particularly in the context of an isolated ocular palsy.⁷

The efficacy of surgical intervention was clear in our patient. When he was examined 2 months after transsphenoidal hypophysectomy, his visual acuity was restored to 20/20 in both eyes, with correction. In addition, he had complete resolution of conjunctival injection and proptosis, although bilateral visual field deficits remained (Figure 3). Although progress has been very gradual, continued improvement in visual field deficits was seen at 4 months (Figure 4) and even at 1 year after surgery (Figure 5).

Three unique components of this case function as reminders that disease presentations can sometimes differ from their classical descriptions:

• Pituitary hyperfunction was observed, instead of the more typical hypopituitarism
• Inferior visual field loss was observed within the context of an infrachiasmatic lesion
• The worst headache of the patient's life turned out to be caused by a rare condition that shares features with other neurologic emergencies.

Conclusion

Many studies have demonstrated the seriousness of pituitary apoplexy and its responsiveness to treatment. As illustrated by this case, visual deficits may continue to resolve long after surgical or medical intervention. The substantial, yet often reversible, visual deficits and pituitary dysfunction; the potential for death; and the efficacy of prompt treatment reinforce the need for physicians to be familiar with this uncommon, yet serious, condition.

References

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