What is apoplexy

Apoplexy is a medical term for sudden loss of consciousness as a result of an acute vascular disturbance caused by the rupture of an intracerebral artery or its occlusion by thrombosis or embolism. The rupture of an intracerebral artery causing subarachnoid hemorrhage (SAH) may also be a cause. Apoplexy could also mean a sudden severe hemorrhage into any organ. For example, abdominal apoplexy or idiopathic spontaneous intraperitoneal hemorrhage, is a rare and often fatal condition resulting from a variety of disease processes affecting the arterial and venous abdominal vasculature ¹. Adrenal apoplexy caused by massive bleeding into the adrenal gland can cause Addisonian crisis or adrenal crisis, which is a potentially life-threatening condition that results from an acute insufficiency of adrenal hormones (glucocorticoid or mineralocorticoid) and requires immediate treatment ². Cerebellar apoplexy caused by thrombosis of the posterior inferior cerebellar artery ³.

Cerebral apoplexy

Cerebral apoplexy is more commonly known as stroke, is an acute compromise of the cerebral perfusion or vasculature or cerebrovascular accident ⁴. A stroke is a life-threatening medical emergency. Strokes happen when blood flow to your brain stops. Within minutes, brain cells begin to die. There are two kinds of stroke. The more common kind in the United States is called ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain. The other kind, called hemorrhagic stroke, is caused by a blood vessel that breaks and bleeds into the brain. “Mini-strokes” or transient ischemic attacks (TIAs), occur when the blood supply to the brain is briefly interrupted.

• Strokes are a medical emergency and urgent treatment is essential.
• A stroke can cause lasting brain damage, long-term disability, or even death.
• Stroke is the no. 3 cause of death in the United States. More than 140,000 people die each year from stroke in the United States.
  
• Stroke is the leading cause of serious, long-term disability in the United States.
• Each year, approximately 795,000 people suffer a stroke. About 600,000 of these are first attacks, and 185,000 are recurrent attacks.
• Nearly three-quarters of all strokes occur in people over the age of 65. The risk of having a stroke more than doubles each decade after the age of 55.
• Strokes can and do occur at ANY age. Nearly one fourth of strokes occur in people under the age of 65.
• Stroke death rates are higher for African-Americans than for whites, even at younger ages.
• On average, someone in the United States has a stroke every 40 seconds.
• Stroke accounted for about one of every 17 deaths in the United States in 2006. Stroke mortality for 2005 was 137,000.
• The risk of ischemic stroke in current smokers is about double that of nonsmokers after adjustment for other risk factors.
• Atrial fibrillation (AF) is an independent risk factor for stroke, increasing risk about five-fold.
• High blood pressure is the most important risk factor for stroke.

The sooner a person receives treatment for a stroke, the less damage is likely to happen.

If you suspect that you or someone else is having a stroke, call your local emergency number immediately and ask for an ambulance.

Other symptoms and signs of stroke may include:

• Sudden numbness, paralysis or weakness of the face, arm or leg (especially on one side of the body)
• Sudden loss or blurring of vision in one or both eyes
• Dizziness
• Sudden trouble walking, dizziness, loss of balance or coordination
• Sudden confusion, trouble speaking or understanding speech
• Difficulty understanding what others are saying
• Problems with balance and co-ordination
• Difficulty swallowing (dysphagia)
• Sudden and very severe headache resulting in a blinding pain unlike anything experienced before
• Loss of consciousness

However, there may be other causes for these symptoms.

If you have any of these symptoms, you must get to a hospital quickly to begin treatment. Acute stroke therapies try to stop a stroke while it is happening by quickly dissolving the blood clot or by stopping the bleeding. Post-stroke rehabilitation helps individuals overcome disabilities that result from stroke damage. Drug therapy with blood thinners is the most common treatment for stroke.

Figure 1. Ischemic stroke

Figure 2. Hemorrhagic stroke

Figure 3. Transient ischemic attack (TIA) or mini stroke

Cerebral apoplexy causes

A stroke occurs when the blood supply to your brain is interrupted or reduced. This deprives your brain of oxygen and nutrients, which can cause your brain cells to die.

A stroke may be caused by a blocked artery (ischemic stroke) or the leaking or bursting of a blood vessel (hemorrhagic stroke). Some people may experience only a temporary disruption of blood flow to their brain (transient ischemic attack, or TIA). This causes what’s known as a mini-stroke, often lasting between a few minutes and several hours. TIAs should be treated urgently, as they’re often a warning sign you’re at risk of having a full stroke in the near future. Seek medical advice as soon as possible, even if your symptoms resolve.

There are two main causes of strokes:

1. Ischemic stroke – where the blood supply is stopped because of a blood clot, accounting for 85% of all cases
2. Hemorrhagic stroke– where a weakened blood vessel supplying the brain bursts

Risk factors for cerebral apoplexy

Many factors can increase your risk of a stroke. Some factors can also increase your chances of having a heart attack. Potentially treatable stroke risk factors include:

Lifestyle risk factors

• Being overweight or obese
• Physical inactivity
• Heavy or binge drinking
• Use of illicit drugs such as cocaine and methamphetamines

Medical risk factors

• High blood pressure (hypertension) — the risk of stroke begins to increase at blood pressure readings higher than 120/80 millimeters of mercury (mm Hg). Your doctor will help you decide on a target blood pressure based on your age, whether you have diabetes and other factors.
• Cigarette smoking or exposure to secondhand smoke.
• High cholesterol.
• Diabetes.
• Obstructive sleep apnea — a sleep disorder in which the oxygen level intermittently drops during the night.
• Cardiovascular disease, including heart failure, heart defects, heart infection or abnormal heart rhythm (atrial fibrillation).

Other factors associated with a higher risk of stroke include:

• Personal or family history of stroke, heart attack or transient ischemic attack.
• Being age 55 or older.
• Race — African-Americans have a higher risk of stroke than do people of other races.
• Gender — Men have a higher risk of stroke than women. Women are usually older when they have strokes, and they’re more likely to die of strokes than are men. Also, they may have some risk from some birth control pills or hormone therapies that include estrogen, as well as from pregnancy and childbirth.

Cerebral apoplexy prevention

Knowing your stroke risk factors, following your doctor’s recommendations and adopting a healthy lifestyle are the best steps you can take to prevent a stroke. If you’ve had a stroke or a transient ischemic attack (TIA), these measures may help you avoid having another stroke. The follow-up care you receive in the hospital and afterward may play a role as well.

Many stroke prevention strategies are the same as strategies to prevent heart disease. In general, healthy lifestyle recommendations include:

• Controlling high blood pressure (hypertension). One of the most important things you can do to reduce your stroke risk is to keep your blood pressure under control. If you’ve had a stroke, lowering your blood pressure can help prevent a subsequent transient ischemic attack or stroke.

Exercising, managing stress, maintaining a healthy weight, and limiting the amount of sodium and alcohol you eat and drink are all ways to keep high blood pressure in check.. In addition to recommending lifestyle changes, your doctor may prescribe medications to treat high blood pressure.

• Lowering the amount of cholesterol and saturated fat in your diet. Eating less cholesterol and fat, especially saturated fat and trans fats, may reduce the fatty deposits (plaques) in your arteries. If you can’t control your cholesterol through dietary changes alone, your doctor may prescribe a cholesterol-lowering medication.
• Quitting smoking. Smoking raises the risk of stroke for smokers and nonsmokers exposed to secondhand smoke. Quitting tobacco use reduces your risk of stroke.
• Controlling diabetes. You can manage diabetes with diet, exercise, weight control and medication.
• Maintaining a healthy weight. Being overweight contributes to other stroke risk factors, such as high blood pressure, cardiovascular disease and diabetes. Weight loss of as little as 10 pounds may lower your blood pressure and improve your cholesterol levels.
• Eating a diet rich in fruits and vegetables. A diet containing five or more daily servings of fruits or vegetables may reduce your risk of stroke. Following the Mediterranean diet, which emphasizes olive oil, fruit, nuts, vegetables and whole grains, may be helpful.
• Exercising regularly. Aerobic or “cardio” exercise reduces your risk of stroke in many ways. Exercise can lower your blood pressure, increase your level of high-density lipoprotein cholesterol, and improve the overall health of your blood vessels and heart. It also helps you lose weight, control diabetes and reduce stress. Gradually work up to 30 minutes of activity — such as walking, jogging, swimming or bicycling — on most, if not all, days of the week.
• Drinking alcohol in moderation, if at all. Alcohol can be both a risk factor and a protective measure for stroke. Heavy alcohol consumption increases your risk of high blood pressure, ischemic strokes and hemorrhagic strokes. However, drinking small to moderate amounts of alcohol, such as one drink a day, may help prevent ischemic stroke and decrease your blood’s clotting tendency. Alcohol may also interact with other drugs you’re taking. Talk to your doctor about what’s appropriate for you.
• Treating obstructive sleep apnea, if present. Your doctor may recommend an overnight oxygen assessment to screen for obstructive sleep apnea (OSA). If obstructive sleep apnea is detected, it may be treated by giving you oxygen at night or having you wear a small device in your mouth.
• Avoiding illicit drugs. Certain street drugs, such as cocaine and methamphetamines, are established risk factors for a TIA or a stroke. Cocaine reduces blood flow and can cause narrowing of arteries.

Preventive medications

If you’ve had an ischemic stroke or TIA, your doctor may recommend medications to help reduce your risk of having another stroke. These include:

• Anti-platelet drugs. Platelets are cells in your blood that initiate clots. Anti-platelet drugs make these cells less sticky and less likely to clot. The most commonly used anti-platelet medication is aspirin. Your doctor can help you determine the right dose of aspirin for you. Your doctor may also consider prescribing Aggrenox, a combination of low-dose aspirin and the anti-platelet drug dipyridamole, to reduce the risk of blood clotting. If aspirin doesn’t prevent your TIA or stroke, or if you can’t take aspirin, your doctor may instead prescribe an anti-platelet drug such as clopidogrel (Plavix).

• Anticoagulants. These drugs, which include heparin and warfarin (Coumadin), reduce blood clotting. Heparin is fast-acting and may be used over a short period of time in the hospital. Slower acting warfarin may be used over a longer term. Warfarin is a powerful blood-thinning drug, so you’ll need to take it exactly as directed and watch for side effects. Your doctor may prescribe these drugs if you have certain blood-clotting disorders, certain arterial abnormalities, an abnormal heart rhythm or other heart problems. Other newer blood thinners may be used if your TIA or stroke was caused by an abnormal heart rhythm.

Cerebral apoplexy diagnosis

To determine the most appropriate treatment for your stroke, your emergency team needs to evaluate the type of stroke you’re having and the areas of your brain affected by the stroke. They also need to rule out other possible causes of your symptoms, such as a brain tumor or a drug reaction. Your doctor may use several tests to determine your risk of stroke, including:

Physical examination. Your doctor will ask you or a family member what symptoms you’ve been having, when they started and what you were doing when they began. Your doctor then will evaluate whether these symptoms are still present. Your doctor will want to know what medications you take and whether you have experienced any head injuries. You’ll be asked about your personal and family history of heart disease, transient ischemic attack or stroke.

Your doctor will check your blood pressure and use a stethoscope to listen to your heart and to listen for a whooshing sound (bruit) over your neck (carotid) arteries, which may indicate atherosclerosis. Your doctor may also use an ophthalmoscope to check for signs of tiny cholesterol crystals or clots in the blood vessels at the back of your eyes.

• Blood tests. You may have several blood tests, which tell your care team how fast your blood clots, whether your blood sugar is abnormally high or low, whether critical blood chemicals are out of balance, or whether you may have an infection. Managing your blood’s clotting time and levels of sugar and other key chemicals will be part of your stroke care.
• Computerized tomography (CT) scan. A CT scan uses a series of X-rays to create a detailed image of your brain. A CT scan can show a hemorrhage, tumor, stroke and other conditions. Doctors may inject a dye into your bloodstream to view your blood vessels in your neck and brain in greater detail (computerized tomography angiography).
• Magnetic resonance imaging (MRI). An MRI uses powerful radio waves and magnets to create a detailed view of your brain. An MRI can detect brain tissue damaged by an ischemic stroke and brain hemorrhages. Your doctor may inject a dye into a blood vessel to view the arteries and veins and highlight blood flow (magnetic resonance angiography, or magnetic resonance venography).
• Carotid ultrasound. In this test, sound waves create detailed images of the inside of the carotid arteries in your neck. This test shows buildup of fatty deposits (plaques) and blood flow in your carotid arteries.
• Cerebral angiogram. In this test, your doctor inserts a thin, flexible tube (catheter) through a small incision, usually in your groin, and guides it through your major arteries and into your carotid or vertebral artery. Then your doctor injects a dye into your blood vessels to make them visible under X-ray imaging. This procedure gives a detailed view of arteries in your brain and neck.
• Echocardiogram. An echocardiogram uses sound waves to create detailed images of your heart. An echocardiogram can find a source of clots in your heart that may have traveled from your heart to your brain and caused your stroke. You may have a transesophageal echocardiogram. In this test, your doctor inserts a flexible tube with a small device (transducer) attached into your throat and down into the tube that connects the back of your mouth to your stomach (esophagus). Because your esophagus is directly behind your heart, a transesophageal echocardiogram can create clear, detailed ultrasound images of your heart and any blood clots.

Cerebral apoplexy treatment

Emergency treatment for stroke depends on whether you’re having an ischemic stroke blocking an artery — the most common kind — or a hemorrhagic stroke that involves bleeding into the brain.

Ischemic stroke

To treat an ischemic stroke, doctors must quickly restore blood flow to your brain.

Emergency treatment with medications

Therapy with clot-busting drugs must start within 3 hours if they are given into the vein — and the sooner, the better. Quick treatment not only improves your chances of survival but also may reduce complications. You may be given:

• Aspirin. Aspirin is an immediate treatment given in the emergency room to reduce the likelihood of having another stroke. Aspirin prevents blood clots from forming.

• Intravenous injection of tissue plasminogen activator (TPA). Some people can benefit from an injection of a recombinant tissue plasminogen activator (TPA), also called alteplase. An injection of TPA is usually given through a vein in the arm. This potent clot-busting drug needs to be given within 4.5 hours after stroke symptoms begin if it’s given in the vein. TPA restores blood flow by dissolving the blood clot causing your stroke, and it may help people who have had strokes recover more fully. Your doctor will consider certain risks, such as potential bleeding in the brain, to determine if TPA is appropriate for you.

Emergency procedures

Doctors sometimes treat ischemic strokes with procedures that must be performed as soon as possible, depending on features of the blood clot:

• Medications delivered directly to the brain. Doctors may insert a long, thin tube (catheter) through an artery in your groin and thread it to your brain to deliver TPA directly into the area where the stroke is occurring. The time window for this treatment is somewhat longer than for intravenous TPA but is still limited.

• Mechanical clot removal. Doctors may use a catheter to maneuver a tiny device into your brain to physically break up or grab and remove the clot.

However, recent studies suggest that for most people, delivering medication directly to the brain (intra-arterial thrombolysis) or using a device to break up or remove clots (mechanical thrombectomy) may not be beneficial. Researchers are working to determine who might benefit from this procedure.

Other procedures to decrease your risk of having another stroke

To decrease your risk of having another stroke or transient ischemic attack, your doctor may recommend a procedure to open up an artery that’s narrowed by fatty deposits (plaques). Doctors sometimes recommend the following procedures to prevent a stroke.

Options will vary depending on your situation:

• Carotid endarterectomy. In a carotid endarterectomy, a surgeon removes plaques from arteries that run along each side of your neck to your brain (carotid arteries). In this procedure, your surgeon makes an incision along the front of your neck, opens your carotid artery and removes plaques that block the carotid artery. Your surgeon then repairs the artery with stitches or a patch made from a vein or artificial material (graft). The procedure may reduce your risk of ischemic stroke. However, a carotid endarterectomy also involves risks, especially for people with heart disease or other medical conditions.

• Angioplasty and stents. In an angioplasty, a surgeon gains access to your carotid arteries most often through an artery in your groin. Here, he or she can gently and safely navigate to the carotid arteries in your neck. A balloon is then used to expand the narrowed artery. Then a stent can be inserted to support the opened artery.

Hemorrhagic stroke

Emergency treatment of hemorrhagic stroke focuses on controlling your bleeding and reducing pressure in your brain. Surgery also may be performed to help reduce future risk.

Emergency measures

If you take warfarin (Coumadin) or anti-platelet drugs such as clopidogrel (Plavix) to prevent blood clots, you may be given drugs or transfusions of blood products to counteract the blood thinners’ effects. You may also be given drugs to lower pressure in your brain (intracranial pressure), lower your blood pressure, prevent vasospasm or prevent seizures.

Once the bleeding in your brain stops, treatment usually involves supportive medical care while your body absorbs the blood. Healing is similar to what happens while a bad bruise goes away. If the area of bleeding is large, your doctor may perform surgery to remove the blood and relieve pressure on your brain.

Surgical blood vessel repair

Surgery may be used to repair blood vessel abnormalities associated with hemorrhagic strokes. Your doctor may recommend one of these procedures after a stroke or if an aneurysm or arteriovenous malformation (AVM) or other type of vascular malformation caused your hemorrhagic stroke:

• Surgical clipping. A surgeon places a tiny clamp at the base of the aneurysm, to stop blood flow to it. This clamp can keep the aneurysm from bursting, or it can prevent re-bleeding of an aneurysm that has recently hemorrhaged.
• Coiling (endovascular embolization). In this procedure, a surgeon inserts a catheter into an artery in your groin and guides it to your brain using X-ray imaging. Your surgeon then guides tiny detachable coils into the aneurysm (aneurysm coiling). The coils fill the aneurysm, which blocks blood flow into the aneurysm and causes the blood to clot.
• Surgical arteriovenous malformation (AVM) removal. Surgeons may remove a smaller AVM if it’s located in an accessible area of your brain, to eliminate the risk of rupture and lower the risk of hemorrhagic stroke. However, it’s not always possible to remove an AVM if its removal would cause too large a reduction in brain function, or if it’s large or located deep within your brain.
• Intracranial bypass. In some unique circumstances, surgical bypass of intracranial blood vessels may be an option to treat poor blood flow to a region of the brain or complex vascular lesions, such as aneurysm repair.
• Stereotactic radiosurgery. Using multiple beams of highly focused radiation, stereotactic radiosurgery is an advanced minimally invasive treatment used to repair vascular malformations.

Pituitary apoplexy

Pituitary apoplexy also known as pituitary infarction is a rare vision and life threatening disorder where bleeding occurs in the pituitary gland and/or blood flow to the pituitary gland is blocked ⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹. Apoplexy means “sudden death” usually caused by bleeding into an organ or loss of blood flow to an organ ¹¹. The term pituitary apoplexy refers to the “sudden death” of the pituitary gland, usually caused by an acute ischemic infarction or hemorrhage. It is important to note that pituitary apoplexy may be divided into hemorrhagic or ischemic, each with unique neuroimaging findings, and some patients have elements of both ⁶. Pituitary apoplexy is commonly caused by bleeding inside a benign (non-cancerous) tumor of the pituitary called pituitary adenoma or pituitary neuroendocrine tumor ⁸, ⁹, ¹⁰. Pituitary adenomas are very common with more than 10,000 pituitary tumors being diagnosed each year in the United States and are often not diagnosed because these tumors are small and never cause any symptoms or health problems ¹². When examining people who have died or who have had imaging tests (like MRI scans) of their head for other health problems, doctors have found that as many as 1 in 4 people may have a pituitary adenoma without knowing it ¹². Pituitary tumors can occur in people of any age including in children, but they are most often found in older adults ¹². The pituitary is damaged when the tumor suddenly enlarges. It either bleeds into the pituitary or blocks blood supply to the pituitary. The larger the tumor, the higher the risk for future pituitary apoplexy. When pituitary bleeding occurs in a woman during or right after childbirth, it is called Sheehan syndrome. This is a very rare condition.

Pituitary apoplexy is a rare event ¹⁰. According to recent epidemiological studies, the prevalence of pituitary apoplexy is about 6.2 cases per 100,000 in Banbury Oxfordshire, United Kingdom ¹³ and its incidence 0.17 episodes per 100,000 per year in Northern Finland ¹⁴. Between 2% and 12% of patients with all types of pituitary adenoma experience apoplexy and the diagnosis of pituitary tumor was unknown at time of apoplexy in more than 3 out of 4 cases ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹, ²², ²³, ²⁴, ²⁵, ²⁶, ²⁷, ²⁸, ²⁹, ³⁰, ³¹, ³², ³³, ³⁴, ³⁵, ³⁶, ³⁷, ³⁸, ³⁹, ⁴⁰. If the nonfunctioning pituitary adenomas (often incidentalomas) were already known and that a decision was made to manage them conservatively, the risk of pituitary apoplexy was calculated to be between 0.2 and 0.6 events per 100 person-years in 2 metaanalyses ⁴¹, ⁴².

Pituitary apoplexy is characterized by a sudden onset of headache, visual symptoms and vomiting (Apoplexy Triad) with altered mental status, and hormonal dysfunction due to acute hemorrhage or infarction of a pituitary gland ⁶. An existing pituitary adenoma usually is present. Sudden-onset headache located behind the eyes is the most common symptom ⁴³, ⁴⁴. Several mechanisms have been theorized to explain the headache in pituitary apoplexy and include involvement of the superior division of the trigeminal nerve inside the cavernous sinus, meningeal irritation, dura-mater compression, or enlargement of sellar walls. Other symptoms include visual acuity impairment and visual field impairment from involvement of the optic nerve or chiasm, hemianopia, diplopia, ptosis, nausea and vomiting, altered mental status, and hormonal dysfunction ⁴⁵, ⁴⁶, ⁴⁴, ⁴⁷, ⁴⁸, ⁴⁹. Many patients complain of double vision, which is caused by extrinsic compression of one or several of the extraocular nerves traversing the cavernous sinus. The oculomotor is the nerve most commonly affected ⁵⁰. Patients will have ptosis and lateral eye deviation, sometimes accompanied by pupillary dilation of the affected eye.

Pituitary apoplexy diagnosis is based on history, examination, and neuro-imaging. Radiographic features of pituitary apoplexy include enlargement of the pituitary gland, with or without bleeding ⁵¹. Macroscopic hemorrhage is common and occurs in about 85%. It shows peripheral enhancement around a non-enhancing infarcted center ⁵¹. Surrounding edema may be seen in the optic tracts and chiasm.

Pituitary apoplexy treatment can vary between conservative management to prompt resuscitation, including administration of intravenous corticosteroids to avoid Addisonian crisis and neurosurgical intervention, which generally is by the trans-sphenoidal route ⁷.

For patients presenting with neurological changes from pituitary tumor apoplexy, urgent surgical intervention is commonly performed for tumor resection, and optic apparatus decompression ⁵². Pituitary apoplexy treatment aims are to improve symptoms and relieve compression of local structures. For this purposes, surgical decompression is the most rapid way for achieving them ⁵³, ⁵². It has been reported that the surgical outcomes of patients with pituitary apoplexy may be quite poor when compared to the surgical outcomes of patients operated for a pituitary tumor without pituitary apoplexy ⁵⁴. Accordingly, a complete recovery of oculomotor nerve (the third cranial nerve) palsies has been described in 31–57% of patients presenting pituitary apoplexy after surgery ⁵², ⁵⁵, ⁵⁶, normalization of visual acuity in about 50% of the cases ⁵⁵, ⁵⁶, anterior pituitary function normalization in more than 50% of cases and complete tumor resection in most of the patients ⁵⁷, ⁵⁸.

Acute pituitary apoplexy can be life-threatening if its not diagnosed or treated in a timely manner. The prognosis (outlook) is good for people who is diagnosed and treated in a timely manner. When appropriately managed, visual symptoms often improve, but long-term (chronic) pituitary deficiency may remain ⁵⁹.

Figure 4. Pituitary apoplexy

Footnote: Magnetic resonance image scans of a patient categorized as group 3 showing pituitary mass with low signal intensity in the T2-weighted image (A) and high signal intensity in the T1 weighted images (B) indicating acute hemorrhage.

[Source ⁶⁰ ]

Figure 5. Pituitary apoplexy

Footnotes: 30 year old male with one month blurred vision and increasing headache. A 19 x 23 x 25 mm ovoid mass lesion is seen in the pituitary fossa with suprasellar extension (necrotic pituitary macroadenoma). The mass is not clearly separate from the anterior portion of the pituitary, which cannot be identified. A solid component is located anterolaterally (towards the left) and this component enhances. The optic chiasm is markedly compressed, draped over the superior aspect of the mass lesion. The mass is T1 and T2 hyperintense centrally with no significant enhancement post contrast. There are a few fine internal septations. No restricted diffusion within the mass. No calcifications. The remaining imaged brain, including posterior fossa structures, are normal. The white matter in the peri trigonal regions is thinned with undulation of the lateral margins of the lateral ventricles. This patient went on to have transphenoidal surgery. Final diagnosis is pituitary tumor (non-functioning gonadotroph cell adenoma).

[Source ⁶¹ ]

Figure 6. Pituitary Ring Sign

Footnotes: A 55-year-old man presented with acute onset of severe headache, diplopia, nausea, and vomiting. The neuro-ophthalmologic examination showed a visual acuity with correction at the bedside of 20/50 (right eye), 20/70 (left eye), with normal color vision and confrontational visual fields. Pupils were normal without a relative afferent pupillary defect. Ocular motility, slit-lamp, and ophthalmoscopic examinations were normal. Post-contrast sagittal T1-weighted scan shows sphenoid sinus roof mucosal thickening. The horizontal arrow shows the “pituitary ring sign”; the vertical arrow shows sphenoid sinus roof mucosal thickening.

[Source ⁶² ]

What is the pituitary gland?

The pituitary is a small gland at the base of the skull, just below the brain and above the nasal passages and the fleshy back part of the roof of the mouth (known as the soft palate). The pituitary sits in a tiny bony space called the sella turcica. The nerves that connect the eyes to the brain, called the optic nerves, pass just above it. The pituitary is connected directly to part of the brain called the hypothalamus. This provides a key link between the brain and the endocrine system, a collection of glands and organs in the body that make hormones. Hormones are substances released into the blood that control how other organs work. The hypothalamus releases hormones into tiny blood vessels connected to the pituitary gland. These then cause the pituitary to make its own hormones. The pituitary is considered the “master control gland” because it makes the hormones that control the levels of other hormones made by most of the endocrine glands in the body.

The pituitary gland has 2 parts, the anterior pituitary and the posterior pituitary. Each part has distinct functions.

Figure 7. The pituitary gland location

Figure 8. Pituitary gland

Figure 9. The hypothalamus and pituitary gland (anterior and posterior) endocrine pathways and target organs

[Source ⁶³ ]

The anterior pituitary

Most pituitary tumors start in the larger, front part of the pituitary gland known as the anterior pituitary. This part of the gland makes several hormones:

• Growth hormone (GH, also known as somatotropin) promotes body growth during childhood. If a child or teen’s body makes too much growth hormone, they will grow very tall (a condition called gigantism). If an adult’s body makes too much growth hormone, the bones of the hands, feet, and face can grow larger than normal, distorting their features. This condition is called acromegaly.
  Thyroid-stimulating hormone (TSH, also called thyrotropin) stimulates the thyroid gland to release thyroid hormones, which regulate body metabolism. Too much of these hormones makes you hyperactive and shaky, and too little makes you sluggish. If a pituitary tumor makes too much TSH, it can cause hyperthyroidism (an overactive thyroid gland).
• Adrenocorticotropic hormone (ACTH, also known as corticotropin) causes the adrenal glands to make steroid hormones (such as cortisol). Too much ACTH from a pituitary tumor causes Cushing’s disease, the symptoms of which can include rapid weight gain and the build-up of fat in certain parts of the body, as well as high blood pressure and diabetes.
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are also called gonadotropins. In women their main effects are on the ovaries, where they control ovulation (the release of eggs) and the production of the hormones estrogen and progesterone. In men, LH and FSH control testosterone and sperm production in the testicles.
• Prolactin causes milk production in the female breast. Its function in men is not known. Pituitary tumors that make prolactin can cause reproductive problems, as well as milk production in both women and men.

The posterior pituitary

The smaller, back part of the pituitary gland is really an extension of brain tissue from the hypothalamus. The posterior pituitary stores and releases hormones made by the hypothalamus (vasopressin and oxytocin) into the bloodstream.

• Vasopressin (also called antidiuretic hormone, or ADH) causes the kidneys to keep water in the body, rather than losing it all in the urine. When vasopressin levels are low, a person urinates too much and becomes dehydrated. This condition is called diabetes insipidus. Vasopressin also can raise blood pressure by constricting blood vessels. It might have other functions as well.
• Oxytocin causes the uterus to contract in women during childbirth and the breasts to release milk when a woman breastfeed her baby. It might also have other functions in both men and women.

Tumors rarely start in the posterior pituitary.

Pituitary apoplexy causes

A pre-existing pituitary adenoma is usually found in cases of pituitary apoplexy ⁷. In the majority of the cases, the patients are unaware of the pituitary tumor ²⁸.

Several predisposing or contributing factors for pituitary apoplexy include ⁶⁴, ⁷:

• endocrine stimulation tests ⁶⁵
• head trauma
• bromocriptine or cabergoline treatment ⁶⁶, ⁶⁷
• gonadotropin-releasing hormone treatment ⁶⁸
• lumbar fusion in the prone position ⁶⁹, ⁷⁰
• pregnancy ⁷¹, ⁷²
• pituitary irradiation ⁷³
• anticoagulation ⁶⁴
• thrombocytopenia (low platelet level) ⁷⁴, ⁷⁵
• erectile dysfunction medications ⁷⁶

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. Sheehan syndrome occurs in postpartum women in which there is necrosis of the pituitary gland secondary to ischemia after significant bleeding during childbirth. It will present with adrenal insufficiency, hypothyroidism, and hypopituitarism, but rarely with visual changes. Most of the time, this entity is not included as a pituitary apoplexy as the gland did not have a pre-existing tumor, and visual symptoms are extremely rare. Sheehan syndrome is regarded as a neurologic emergency and is potentially lethal.

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.

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” ⁶².

Pituitary 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.

Okuda reported one woman with a giant pituitary adenoma who underwent triple bolus stimulation test with luteinizing hormone-releasing hormone, thyrotropin-releasing hormone (TRH), and insulin ⁷⁷. 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 ⁷⁷.

Some scientists associate pituitary apoplexy with administration of gonadotropin hormone-releasing hormone (GnRH). Corticotropin-releasing hormone (CRH) 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 resulting in internal carotid artery occlusion has been reported due to the mass compressing the bilateral cavernous sinuses, resulting in obliteration of the cavernous portion of the right internal carotid artery ⁷⁸.

Pituitary apoplexy during induction chemotherapy for acute myeloid leukemia has been reported by Silberstein and colleagues ⁷⁹.

Pituitary apoplexy has been reported after cardiac bypass surgery by Thurtell and colleagues ⁸⁰.

Brar and Garg reported a case of pituitary apoplexy in a young man who ascended to high altitude gradually, even after proper acclimatization ⁸¹.

Pituitary apoplexy has been reported in a patient with dengue fever and thrombocytopenia ⁸². Kruljac et al reported a patient with pituitary metastasis presenting as ischemic pituitary apoplexy after heparin-induced thrombocytopenia ⁸³.

Weisberg warns that radiotherapy is potentially hazardous in pituitary tumors with prior hemorrhagic, necrotic, or cystic changes ⁸⁴.

Some believe that pituitary 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 ⁸⁵. Both may result in brain ischemia.

Pituitary apoplexy risk factors

Pituitary apoplexy risk factors include ⁵, ⁸⁶:

• Pituitary Tumor
• Non-functioning pituitary macroadenoma
• Certain functional tumors
• Hypertension and/or hypotension
• Surgery
• Cardiac surgery (heart lung bypass; coronary artery grafts)
• Cerebral angiography
• Major orthopedic procedures
• Drugs
• Endocrine stimulation tests (thyrotropin releasing hormone stimulation; insulin tolerance test)
• Anticoagulation therapy
• Estrogen
• Head Trauma
• Changes in intracranial pressure
• Pregnancy and Delivery (Sheehan syndrome)
• Infections
• Dengue fever
• Hypophyisitis
• Radiation therapy
• Medical treatment of a prolactinoma (especially with bromocriptine) ⁸⁷.

Pituitary apoplexy pathophysiology

Pituitary apoplexy pathophysiology is not fully understood, but it is noteworthy that most cases involve patients with pituitary adenomas or, less commonly, in a nonadenomatous gland from infarction or hemorrhage ⁸⁸, ⁸⁹, ²¹, ²⁶, ⁹⁰.

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. It is more common in macroadenomas and nonfunctioning adenomas, and it rarely has been reported in microadenomas ⁹¹.

Some theorized that a gradually enlarging pituitary tumor becomes impacted at the diaphragmatic notch, compressing and distorting the hypophyseal stalk and its vascular supply ⁹². This deprives the anterior pituitary gland and the tumor itself of its 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 ⁹². This explanation is doubtful, since most tumors that undergo apoplexy are slow growing.

Nevertheless, pituitary adenomas are prone to bleed and undergo infarction and necrosis, possibly because pituitary gland has this unique rich vascular structure and/or because pituitary tumors which have a high-energy requirement may outgrow their blood supply or because ischemia (and thus infarction) occurs after compression of infundibular or superior hypophyseal vessels against the sellar diaphragm by the expanding tumor mass with intrinsically poor vascularity ⁹⁰, ⁹³, ⁹⁴.

Moreover, as recently demonstrated, pituitary tumor cells are particularly sensitive to glucose deprivation ⁹⁵. In this setting, all clinical situations that acutely decrease systemic blood pressure, such as cardiac, vascular, or orthopedic surgery may decrease blood supply to the pituitary adenoma and precipitate pituitary apoplexy ⁹². Dynamic tests or hypoglycemia that acutely increase the metabolic needs of the tumor may also precipitate pituitary apoplexy, as well as severe vomiting/diarrhea with concomitant increased Valsalva pressure.

The inherent fragility of pituitary tumor blood vessels may also explain the hemorrhagic tendency ⁹⁶. The blood vessels of pituitary adenomas show signs of incomplete maturation and poor fenestration, and their basal membranes are often ruptured ⁴⁵, ⁹⁷, ⁹⁸. Immunohistochemical expression of vascular endothelial growth factor was found to correlate positively with the risk of pituitary hemorrhage ⁹⁹. Pituitary tumor-transforming gene (PTTG), which is correlated to vascularization and expression of vascular endothelial growth factor ¹⁰⁰, is also overexpressed in pituitary adenomas ¹⁰¹, ¹⁰². Fetal liver kinase 1, a vascular marker, is also expressed, particularly in nonfunctioning pituitary adenomas, particularly in older subjects ¹⁰³, as is nestin, another vascular marker ¹⁰⁴.

Whatever the mechanism, the extent of hemorrhage and necrosis will produce an increase in intrasellar pressure ²¹, ⁴⁵, ¹⁰⁵, ¹⁰⁶, ¹⁰⁷, which in turn leads to more or less pronounced compression of neighboring structures, thus explaining the broad clinical spectrum, from “classical” acute pituitary apoplexy to totally silent necrotic and/or hemorrhagic pituitary adenomas found only on pathological examination.

Pituitary apoplexy symptoms

Pituitary apoplexy usually has a short period of symptoms (acute), which can be life threatening. 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.

Pituitary apoplexy symptoms during the acute phase of apoplexy often include ⁵, ¹⁰⁸:

• Severe headache (worst of your life) (95%). Sudden-onset headache located behind the eyes is the most common symptom ⁴³, ⁴⁴. Several mechanisms have been theorized to explain the headache in pituitary apoplexy and include involvement of the superior division of the trigeminal nerve inside the cavernous sinus, meningeal irritation, dura-mater compression, or enlargement of sellar walls. Other symptoms include decreased visual acuity, hemianopia, diplopia, ptosis, nausea and vomiting, altered mental status, and hormonal dysfunction.[2][28][29][30][31] Many patients complain of double vision, which is caused by extrinsic compression of one or several of the extraocular nerves. The oculomotor is the nerve most commonly affected.[23] Patients will have ptosis and lateral eye deviation, sometimes accompanied by pupillary dilation of the affected eye.
• Paralysis of the eye muscles, causing double vision (ophthalmoplegia) or problems opening an eyelid (78%)
• Loss of peripheral vision (52%) or loss of all vision in one or both eyes (64%)
• Low blood pressure (hypotension) (95%), nausea, loss of appetite, and vomiting (70%) from acute adrenal insufficiency
• Personality changes due to sudden narrowing or spasm of one of the arteries in the brain (anterior cerebral artery)
• Hemiplegia rare
• Meningismus rare
• There is one case report of stubborn hiccups in association with pituitary apoplexy ¹⁰⁹

Less commonly, pituitary dysfunction may appear more slowly. In Sheehan syndrome, for example, the first symptom may be a failure to produce milk caused by a lack of the hormone prolactin after delivery.

As the hemorrhagic infarct resolves, over time problems with other pituitary hormones may develop, causing hypopituitarism symptoms ¹⁰⁸:

• Growth hormone deficiency
• Adrenal insufficiency (if not already present or treated)
• Hypogonadism (body’s sex glands produce little or no hormones)
• Hypothyroidism (thyroid gland does not make enough thyroid hormone)

In rare cases, when the posterior (back part) of the pituitary is involved, symptoms may include ¹⁰⁸:

• Failure of the uterus to contract to give birth to a baby (in women)
• Failure to produce breast milk (in women)
• Frequent urination and severe thirst (diabetes insipidus)

Pituitary apoplexy complications

Complications of untreated pituitary apoplexy can include:

• Adrenal crisis also called Addisonian crisis (condition that occurs when there is not enough cortisol, a hormone produced by the adrenal glands)
• Vision loss
• Frontal lobe herniation and chiasmal herniation have been reported ¹¹⁰

If other missing hormones are not replaced, symptoms of hypothyroidism and hypogonadism may develop, including infertility.

In pituitary apoplexy, the most impacting clinical problem is the lack of secretion of adrenocorticotropic hormone (ACTH), which occurs in more than two-thirds of the patients with pituitary apoplexy ⁷. The lack of secretion causes a cessation of cortisol secretion by the adrenal gland, which produces a variety of symptoms called “adrenal crisis” ⁴⁶, ⁴³. The patient may have nausea and vomiting, abdominal pain, bradycardia and hypotension, hypothermia, lethargy, and sometimes coma.

Pituitary apoplexy diagnosis

Your doctor will perform a physical exam and ask about your symptoms.

Tests that may be ordered include:

• Eye exams
• Magnetic resonance imaging (MRI) or computed tomographic (CT) scan of your brain

Neuroimaging

Magnetic resonance imaging (MRI) scan, as seen in Figure 1 above is the most sensitive imaging study for evaluating the pituitary gland, possibly visualizing hemorrhage not seen on CT scan ⁴⁶, ⁵⁰. 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. A characteristic MRI finding in ischemic (nonhemorrhagic) pituitary apoplexy is an enlarged pituitary gland bulging under the optic chiasm with peripheral enhancement surrounding a hypointense gland. Vaphiades coined the phrase “pituitary ring sign” to denote this MRI appearance (see Figure 6) ⁶². Vaphiades retrospectively reviewed the cranial MRIs of 3 patients with ischemic (nonhemorrhagic) pituitary apoplexy; all 3 patients displayed the “pituitary ring sign” ⁶². The term “pituitary ring sign” is used to describe an enlarged pituitary gland bulging under the optic chiasm, with peripheral enhancement surrounding a hypointense gland ⁶². This MRI appearance was first noted in 1995 by Lavallée et al. in a patient with Sheehan syndrome on a contrast-enhanced computed tomography (CT) scan and on a T1-weighted contrast-enhanced MRI scan and thought to be unique to ischaemic apoplexy in patients with Sheehan syndrome ¹¹¹. However, the ring sign is not specific for pituitary infarction, because it can be seen in association craniopharyngioma ¹¹² in addition to lymphocytic hypophysitis, pituitary abscess, and pituitary adenoma that has not undergone apoplexy ¹¹³. Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland, commonly manifesting late in pregnancy or during the postpartum period. It can mimic pituitary adenoma. In the majority of cases, the lymphocytic hypophysitis diagnosis is made after pituitary surgery for suspected pituitary adenoma ¹¹⁴.

Sphenoid sinus mucosal thickening, occurring in the setting of pituitary apoplexy, was first described by Arita et al. in 2001 ¹¹⁵. They retrospectively evaluated 14 patients with pituitary apoplexy. The mucosa of the sphenoid sinus on MRI had thickened the compartment just beneath the sella turcica in 9 of 11 patients obtained within 7 days after the onset of apoplectic symptoms ¹¹⁵. Controls consisted of MR images obtained in 100 consecutive patients with pituitary adenomas but without apoplectic symptoms. Included in this group were 58 functioning and 42 non-functioning pituitary adenomas. Fifteen patients experienced thickening of the sphenoid sinus mucosa, including five with some apparent pansinusitis. The incidence of mucosal thickening of the sphenoid sinus in the patients with apoplexy was significantly greater than that in the patients without apoplexy ¹¹⁵. On histopathological specimens in the apoplexy patients, the thickened sphenoid sinus mucosa demonstrates a swollen sub-epithelial layer presumably responsible for the rim of MRI gadolinium enhancement ¹¹⁵. In 2006, Liu et al. ²³ performed a retrospective review of 28 patients with pituitary apoplexy. Thickening of sphenoid sinus mucosa was present in 22 (79%) of these patients. They also noted that patients with thickened sphenoid sinus mucosa had larger tumours, a higher rate of cranial nerve deficits at presentation than those without mucosal thickening, and a higher rate of hypopituitarism and subsequent long-term hormone replacement therapy compared with those patients without thickened mucosa ²³. In 2012, Agrawal et al. ¹¹⁶ concluded that there is a temporal association with the radiographic finding of sphenoid sinus mucosal thickening and pituitary apoplexy and that sphenoid sinus mucosal thickening may precede an apoplectic event. Each sign, “pituitary ring sign” and “sphenoid sinus mucosal thickening”, alone may exist in patients with or without pituitary apoplexy, yet presence of both signs together in the appropriate clinical context is a strong predictor of pituitary apoplexy ⁶². This is important because timely diagnosis treatment of pituitary apoplexy may be vision- and life-saving ⁶² .

Kaplun and colleagues reported the MRI evolution of pituitary changes in 2 patients with Sheehan syndrome ¹¹⁷. The first case initially had the pituitary ring sign, although MRI later showed an empty sella with shrinkage of the pituitary.

CT scanning generally is the initial imaging study of choice in the emergency department for patients who present with sudden-onset severe headache, visual loss, and/or ophthalmoplegia suggestive of subarachnoid hemorrhage (SAH). CT scanning can help to exclude subarachnoid hemorrhage (SAH) from an aneurysm by showing an intrasellar mass with hemorrhagic components, seen in 80% of pituitary apoplexy cases ⁴³.

Binning and colleagues reported 6 patients with Rathke cleft cyst apoplexy presenting with the clinical and imaging features of both hemorrhagic and nonhemorrhagic pituitary apoplexy ¹¹⁸.

Liu et al ¹¹⁹ reported spontaneous partial or complete radiological disappearance of adenoma following pituitary apoplexy without the use of dopaminergic agonists (which may result in regression of pituitary adenoma).

Blood tests

Pituitary hormonal evaluation is required, as nearly 80% of patients present with a deficiency of at least one of the anterior pituitary hormones ⁸. The most common deficiencies are growth hormone deficit in 90% of the patients and ACTH (adrenocorticotropic hormone) deficit in 70% of them ⁴⁶, ⁴³, ¹²⁰.

Blood tests will be done to check levels of:

• ACTH (adrenocorticotropic hormone)
• Cortisol
• FSH (follicle-stimulating hormone)
• Growth hormone
• LH (luteinizing hormone)
• Prolactin
• TSH (thyroid-stimulating hormone)
• Insulin-like growth factor-1 (IGF-1)
• Sodium
• Osmolarity in blood and urine

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 ⁸⁹. By immunostaining criteria, null-cell adenomas were the most frequent tumor type found.

Pituitary apoplexy differential diagnosis

Several conditions have to be excluded as they can present with similar visual, ophthalmoplegic, and headache symptoms that occur in pituitary apoplexy. Some of the conditions will only require medical treatment, while in others, the surgical treatment is completely different.

• Rathke’s cleft cyst ¹²¹, ¹²², ¹²³
• Temporal arteritis ¹²⁴
• Aneurysm
• Craniopharyngioma
• Subarachnoid hemorrhage (SAH) ¹²⁵
• Meningitis ¹²⁶ or encephalitis
• Cavernous venous sinus thrombosis
• Basilar artery infarct
• Hypertensive encephalopathy
• Ophthalmoplegic migraine ¹²⁷
• Retrobulbar neuritis

Pituitary apoplexy treatment

The key to successful management of patients with pituitary apoplexy is a team approach including critical care neurologists, neurosurgeons, neuro-ophthalmologist and endocrinologists. Together each of these specialists provide needed expertise in the management and ongoing care of these patients. Acute secondary adrenal insufficiency is seen in approximately two-thirds of patients and is the major source of mortality associated with this condition. Prompt glucocorticoid replacement is therefor mandatory and should not ne delayed for confirmatory testing. The initial management is stabilization of the hemodynamic status with IV 0.9% NaCl (sodium chloride) boluses to maintain normal tissue perfusion, and usually high dose parenteral glucocorticoids (100 mg hydrocortisone every 8 hourly intravenous). Unless significant cerebral edema is present, hydrocortisone rather than dexamethasone is favored.

Although there is a general consensus that patients with pituitary apoplexy and significant neuro-ophthalmic signs or reduced level of consciousness should have surgical decompression, there is significant controversy in the best timing for the surgical procedure due to lack of good quality outcomes data.

Management of the mass is controversial as some advocate early transsphenoidal surgical decompression in all patients, whereas others adopt a conservative approach for those patients without visual acuity or field defects and with normal consciousness ⁷. Emergency surgery should be reserved for patients with progressive deterioration of consciousness, hypothalamic involvement, and progressive visual worsening ⁷. It has been demonstrated that a significant postoperative clinical improvement is a consequence of a surgical procedure performed as soon as possible ⁵⁰. Decompressive surgery can be delayed but performed within 1 week when visual acuity defects appear stable. If ophthalmoplegia is improving or stable, a conservative strategy could be considered ¹²⁸, ¹²⁹. Microscopic endonasal or sublabial transsphenoidal surgery is commonly used. For very large tumors and those extending over the chiasm or laterally to the temporal fossa, a craniotomy should be used to achieve complete resection. Endoscopic endonasal approaches for pituitary apoplexy are effective ⁴⁸, ¹³⁰, ¹³¹. Patients operated using the endoscopic approach have a similar visual outcome, but a better endocrinological outcome as the viable tumoral component can be removed from restricted areas like the cavernous sinus ¹³². Sometimes, an endoscopic approach can prove difficult to perform if required at late night hours as it needs the collaboration of an otolaryngologist with the neurosurgeon.

Figure 10. Pituitary apoplexy treatment

[Source ¹³³ ]

Immediate medical management

Immediate medical management of patients with pituitary apoplexy includes a careful assessment of fluids and electrolyte balance, ensure hemodynamic stability, and replacement with corticosteroids ¹²⁰.

Medical treatment consists of the following:

• Medically stabilize the patient.
• Immediately evaluate electrolytes, glucose, and pituitary hormones.
• Administer high-dose corticosteroids (most patients have hypopituitarism).
• Administer appropriate endocrinologic replacement therapy alone or combined with transsphenoidal surgical decompression of the tumor.
• Avoid the “head down” position, when possible ¹³⁴.

All patients should receive corticosteroids even if they do not present symptoms of adrenal crisis ⁷. The recommended dose is an intravenous 100–200 mg bolus of hydrocortisone. Additional administration of 50-100 mg every 6 hours should be continued. Alternatively, a continuous intravenous infusion of 2-4 mg/hour can be started after the initial bolus ⁴³.

Surgical care

The management of pituitary apoplexy is controversial in that some advocate early transsphenoidal surgical decompression in all patients, whereas others adopt a conservative approach for selected patients (without visual acuity or field defects and with normal consciousness) ⁴³. Children with pituitary tumor apoplexy has a more aggressive natural history in comparison to adults, and early surgery may reduce its occurrence and improve outcomes ¹³⁵, ¹³⁶.

Evacuation of the tumor by a neurosurgeon should be planned once the patient is medically stable, especially in the setting of altered consciousness, visual acuity, and visual field loss ⁴³, ¹³⁷, ¹³⁸.

Shepard et al ¹³⁹ identified 64 patients with pituitary apoplexy, 47 (73.4%) underwent intended conservative management, while 17 (26.6%) had early surgery. Tumor volumes were greater in the early surgical cohort. Among those with visual acuity and field deficits, visual outcomes were similar between both groups. Conservative management failed in 7 patients (14.9%) and they required surgery ¹³⁹. Younger age, female sex, and patients with field deficits or chiasmal compression were more likely to experience unsuccessful conservative management. The authors concluded that the majority of patients with pituitary apoplexy can be successfully managed without surgical intervention assuming close neurosurgical, radiologic, and ophthalmologic follow-up is available ¹³⁹.

Cavalli et al ¹⁴⁰ retrospectively reviewed 30 patients with pituitary apoplexy; they found that 86.7% of patients presented with visual disturbances (70% acuity, 50% field, 50% diploplia), 10 (33%) patients underwent emergency surgery, and 8 underwent delayed elective surgery. At early and late follow-up, the outcome was not significantly different between groups. The authors concluded that good results are possible with conservative management in selected cases. Emergency surgery provides better visual outcomes and a tumor vertical diameter >35 mm should tip the balance in favor of surgical management in presence of visual deficit ¹⁴⁰.

Follow up

While 80% of patients have residual hypopituitarism following pituitary apoplexy (with or without surgical decompression) some patients do not display immediate evidence of hypopituitarism. In addition, recurrent pituitary apoplexy and pituitary tumor regrowth has been reported to occur ¹³³. MRI of the pituitary should be obtained at 3-6 month intervals until the anatomy is stable and then yearly for 5 years. A month after discharge from the hospital and recovery from the acute event, if necessary, patients are subject to repeat endocrine testing to determine if the endocrine defects persist. Repeat testing will confirm whether the patient needs to remain on life-long hormone replacement therapy.

Pituitary apoplexy prognosis

Acute pituitary apoplexy can be life-threatening if its not diagnosed or treated in a timely manner. The prognosis (outlook) is good for people who is diagnosed and treated in a timely manner. The overall mortality is 1.6% to 1.9% ⁷. Visual acuity, visual field defects, and ophthalmoplegia improve in the majority of the patients after both conservative and surgical decompression ⁵⁹. After surgery, such improvement can be observed in the immediate postoperative period and often continues for several weeks after surgery. Visual recovery has been reported to be less likely in patients presenting with monocular or binocular blindness ⁷. Although visual outcome appears to be better with early intervention as compared to late ¹⁴¹, others found that visual deficits, resolution of oculomotor palsy, recovery from hypopituitarism, or non-neuroendocrine signs and symptoms such as headache and encephalopathy do not depend on the timing of surgery ¹⁴². A complete restoration of the oculomotor palsy usually needs 3 months, while abducens nerve palsy usually needs 6 months ⁵⁰. Overall, visual improvement is seen in 75 to 85% of patients, recovery of normal vision in 38% of patients, and rectification of preoperative oculomotor palsies in 81% of patients ⁴⁸.

Gross total resection and short duration of preoperative headaches are predictors for improvement in postoperative headaches ¹⁴³. Hormonal replacement therapy is needed in 80% of the patients ⁸, ²⁵, ¹⁴². In some cases that are treated conservatively, spontaneous remission of the tumor has occurred, and surgery is not required ¹⁴⁴, ¹⁴⁵. This may be caused by ischemic necrosis of the tumoral tissue ⁷.

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