Man With Headache, Diplopia, Nausea, and Vomiting

A 68-year-old man presents to the emergency department with diplopia and headache of acute onset accompanied by nausea and vomiting. Two days earlier, he presented to another hospital with diplopia. Complete left side third nerve palsy was diagnosed, and he was sent home after noncontrast cerebral CT and MRI scans were interpreted as normal. He has a history of well-controlled hypertension, obstructive sleep apnea treated with a uvulopalatopharyngoplasty, hyperlipidemia, and esophagogastroduodenitis. He denies weakness, numbness, preexisting vision loss, and constitutional symptoms.

The patient is alert and oriented and scores 30 out of 30 on a Mini-Mental State Examination. He has bilateral retro-orbital pain that is more pronounced on the left side and complete left side third nerve palsy.

The right pupil is 3 mm and reactive to 2 mm; the left pupil is 4 mm and fixed. On extraocular muscle examination, with the exception of abduction, the left eye is paretic; the right eye is able to move in all directions. The patient has about 50% ptosis in his left eye with full eyelid closure. A positive corneal reflex is noted bilaterally; other cranial nerves are intact.

He has normal tone and bulk and full strength in all extremities. Sensory, cerebellum, and reflex findings are normal.

Laboratory tests reveal the following abnormal levels: chloride, 81 mmol/L (normal, 101 to 111 mmol/L); sodium, 115 mmol/L (normal, 135 to 145 mmol/L); serum cortisol drawn at 9:35 am, 2.5 µg/dL (normal, 8.7 to 22.4 µg/dL); luteinizing hormone, 0.33 mIU/mL (normal, 1.24 to 8.62 mIU/mL); prolactin, 2.18 ng/mL (normal, 2.64 to 13.13 ng/mL); thyroid-stimulating hormone, 0.11 µIU/mL (normal, 0.34 to 5.6 µIU/mL); free thyroxine, 5.70 ng/dL (normal, 5.93 to 13.13 ng/dL); total thyroxine, 5.5 µg/dL (normal, 6.09 to 12.23 µg/dL); and total testosterone, 25 ng/dL (normal, 260 to 1000 ng/dL).

A cerebral angiogram rules out a posterior communicating arterial aneurysm. MRI scans reveal a large sellar mass with suprasellar component and mild mass effect on the left superior cavernous sinus; this is consistent with a pituitary hemorrhagic infarct (Figure 1). The left oculomotor cranial nerve is near the site of left superior cavernous sinus compression. Hemorrhagic pituitary apoplexy is diagnosed.

Results of an adrenocorticotropic hormone (ACTH) stimulation test with 250 µg of synthetic ACTH show 30-minute and 60-minute serum cortisol levels within normal ranges (19.5 µg/dL and 24.7 µg/dL, respectively). These results, coupled with the low baseline cortisol level, indicate recent-onset adrenal insufficiency secondary to loss of ACTH from the pituitary gland. The severe hyponatremia is thought to result from adrenal insufficiency and hypothyroidism. Secondary hypogonadism is also present.

The patient is treated with intravenous hydrocortisone and thyroid supplementation. The hyponatremia slowly corrects within 24 hours. He is discharged after 5 days. Thyroid hormone replacement therapy and oral prednisone, 60 mg/d, are started. One month later, repeated MRI scans show resolution of the mass effect on the left oculomotor nerve (Figure 2). His last follow-up MRI scan showed no significant interval change.

PITUITARY APOPLEXY: AN OVERVIEW

This potentially life-threatening illness requires immediate intervention to prevent serious sequelae. The resulting cranial neuropathies and visual field loss are reversible with timely treatment.¹ In patients with pituitary apoplexy, hemorrhage does not seem to be a helpful prognostic indicator, since mass effect and loss of pituitary function can occur in either the presence or the absence of bleeding.

As many as 90% of pituitary apoplexies occur in patients with a preexisting pituitary adenoma.² In most patients, the tumor remains undetected until the attack.

CLINICAL FEATURES

Headache is usually the most prominent symptom (in about 76% of patients), followed by some degree of visual impairment (in 62% of patients).^2,3 Ocular palsy affects fewer than half of patients and may involve cranial nerves III, IV, and VI as a result of direct compression or entrapment within the cavernous sinus. Isolated unilateral oculomotor paralysis as the presenting feature of a pituitary apoplexy has been described in only a few cases.^4,5

DIAGNOSIS

Differential. In patients with headache, diplopia, nausea, vomiting, and electrolyte disturbances of acute onset, the 2 main diagnostic considerations are pituitary apoplexy and subarachnoid hemorrhage. The interval between the onset of the headache and altered mental status tends to be shorter in subarachnoid hemorrhage, and a bilateral involvement of the third cranial nerves favors pituitary apoplexy. Midbrain infarction, cavernous sinus thrombosis, and bacterial meningitis also need to be considered in the differential diagnosis.

Risk factors. These include head trauma; irradiation; anticoagulation therapy; pregnancy; diabetic ketoacidosis; and use of estrogen supplements, diuretics, or bromocriptine.³ However, the diagnosis usually cannot be made by the history and physical examination alone.

Imaging studies. In the acute setting, noncontrast CT of the head is the most useful diagnostic test. If the scan shows no subarachnoid blood, the test can be repeated with administration of intravenous contrast and thin cuts can be taken through the sellar region. CT scans may demonstrate an inhomogeneous gland, ring enhancement, or a high-density fluid level. However, these findings are not pathognomonic; if the diagnosis remains unclear, order an MRI scan. Although MRI is less reliable in detecting fresh blood, it achieves greater anatomic detail and is better able to detect infarction without hemorrhage.

Diffusion characteristics of pituitary infarction have not been well described. To detect the presence of restricted diffusion in the setting of nonhemorrhagic pituitary infarction, diffusion-weighted MRI has been shown to be a promising technique in the early evaluation of patients who have a suggestive clinical presentation.⁶

Angiographic demonstration of an aneurysm is helpful only when active bleeding is present, because there is a 7.4% co-occurrence of cerebral aneurysms and pituitary adenomas.⁷

CSF findings. Cerebrospinal fluid (CSF) findings are less diagnostic, since xanthochromia and elevated red blood cell counts may be seen in both subarachnoid hemorrhage and pituitary apoplexy. In addition, pleocytosis and an elevated CSF protein level are associated with both pituitary apoplexy and meningitis.

TREATMENT

Pituitary apoplexy is treated with a combination of medical and surgical approaches. Immediate administration of stress doses of corticosteroids is mandatory. If obtundation or uncontrollable electrolyte disturbances develop, immediate neurosurgical decompression can be lifesaving. Another strong indication for surgery is severe and worsening vision loss; only decompressive interventions can completely restore sight.

In this patient, conservative management was selected because he responded rapidly to corticosteroid replacement therapy. In addition, he had isolated ophthalmoplegia with bilateral visual field loss, and ophthalmoplegia usually resolves spontaneously over time.² When a conservative approach is taken, obtain imaging studies several weeks to months after the hematoma resolves. Repeated studies can detect a preexisting pituitary adenoma, which may have been obscured at the time of the initial event. *

References:

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