Epidemiology

Pituitary adenomas are common, with a prevalence of 3% to 27% in various autopsy series. They are rarely diagnosed in life, with a reported incidence of 4 per 100,000 in a Finnish population and a prevalence of 77 per 100,000 in a British one.^1,2 Apoplexy occurs in a minority of such lesions and can occasionally be seen with normal glands. Because of the relative rarity of this condition, pituitary apoplexy may be confused with more common entities such as subarachnoid hemorrhage. Delay in diagnosis and treatment may lead to blindness, permanent cranial nerve palsies, or death.^3,4

Pathophysiology

The two lobes of the pituitary gland sit within an enclosed space known as the sella turcica. Blood supply to this gland is one of the richest of all mammalian tissues.

The anterior lobe receives the portal hypophyseal vessel from the hypothalamus. Differentiated cells in the anterior lobe secrete specific hormones, including growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), thyroid-stimulating hormone (TSH), and gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

The posterior lobe is an extension of the hypothalamus and secretes two hormones: antidiuretic hormone (or arginine vasopressin) and oxytocin. The pituitary stalk and the portal vessel pass through a small diaphragm that separates the sella turcica from the middle fossa. This anatomic arrangement places the pituitary at risk for infarction or hemorrhage when a mass increases pressure in the sella or compresses the stalk and vessels. Higher intrasellar pressures are associated with poor outcomes.

Pituitary tumors are common and many are asymptomatic. They are classified by size (microadenoma, <10 mm; macroadenoma, >10 mm) and by the hormone produced. Of tumors that cause clinical symptoms, the most commonly secreted hormones are PRL, which leads to hypogonadism; GH, which promotes acromegaly; and ACTH, a cause of Cushing disease.

Tumors involved in apoplexy are typically nonfunctional and unsuspected macroadenomas. In patients undergoing an endocrine stimulation test for hypogonadism, hypothyroidism, or adrenal insufficiency, apoplexy may occasionally develop secondary to stimulation of a macroadenoma. Treatment of a pituitary tumor can also precipitate apoplexy, particularly in cases of surgery, irradiation, or bromocriptine administration. Other reported risk factors include pregnancy (Sheehan syndrome), head trauma, recent cardiac surgery, anticoagulation, hypertension, diabetic ketoacidosis, and ovarian stimulation medications.⁵

Most patients with pituitary apoplexy have no identifiable risk factor. Apoplexy may occur in normal glands.

Presenting Signs and Symptoms

Differential Diagnosis and Medical Decision Making

Common neurologic emergencies can be confused with pituitary apoplexy (Box 170.1). The sudden onset of severe headache suggests subarachnoid hemorrhage. Obtundation and meningeal signs suggest meningitis, cerebral hemorrhage, or cerebral venous thrombosis. Cranial nerve findings in the setting of altered mental status may indicate cavernous sinus thrombosis or midbrain infarction. Rare hypothalamic and pituitary compressive or destructive processes may closely mimic apoplexy because of accompanying headaches and visual field deficits. Two such mimics are lymphocytic hypophysitis and Rathke cleft cysts. Pediatric craniopharyngiomas and several primary and metastatic lesions in adults may also compress the pituitary gland and mimic apoplexy. Generally, deficits in visual acuity and visual fields raise suspicion for apoplexy in the appropriate clinical setting.

Diagnostic Testing

Visual acuity and confrontational visual field testing should be performed when the diagnosis of pituitary apoplexy is considered. Samples should be obtained for electrolytes, renal function, liver function, clotting screen, blood counts, random cortisol, thyroxine, TSH, PRL, insulin-like growth factor, GH, LH, FSH, and testosterone in men and estradiol in women.⁸ A non–contrast-enhanced computed tomography scan of the head will exclude the diagnosis of acute subarachnoid hemorrhage. Endocrine simulation testing could worsen the condition and should be deferred. Computed tomography is not sufficiently sensitive to exclude a pituitary process. Contrast-enhanced, diffusion-weighted magnetic resonance imaging allows the best visualization of pituitary tumors and details of the hemorrhage and infarction within them (Fig. 170.1, A and B).⁹

Fig. 170.1 A, Magnetic resonance imaging of the brain showed a 3 × 2 × 2-cm pituitary macroadenoma with bleeding in the center (arrow). B, The tumor shown in coronal section (arrow).

(From Basaria S, Turchin A, Krasner A. Apoplexy in recurrent pituitary adenoma. Postgrad Med J 2001;77:23.)

Management

Parenteral hydrocortisone (100 mg every 6 hours) or dexamethasone (4 mg every 12 hours) is given to decrease tumor edema and treat impending adrenal crisis. Obtunded or comatose patients should be intubated.

There is controversy regarding conservative treatment with steroids versus surgical intervention.^8,10,11 Patients with minimal or improving visual symptoms are sometimes managed medically. Definitive treatment is pituitary decompression, most often through a transsphenoidal approach. The outcome depends on the severity of symptoms at initial evaluation and prompt decompression of the sella turcica. Early diagnosis and treatment improve outcome and visual acuity; any residual hypopituitarism generally persists.^6,7

Disposition

Patients with pituitary apoplexy require emergency consultation with a neurosurgeon experienced in pituitary surgery. Admission to a neurologic intensive care unit should be accompanied by consultation with a medical intensivist and endocrinologist.

Patients with subacute or chronic panhypopituitarism should be evaluated by an endocrinologist for initiation of therapy and further management. Asymptomatic pituitary tumors can be safely followed in the outpatient setting because such cases rarely progress to apoplexy.