Pituitary apoplexy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Pituitary apoplexy is caused by hemorrhage into the pituitary gland. The pituitary gland is a small gland joined to the hypothalamus at the base of brain. The pituitary produces many of the hormones that control essential body processes. Pituitary apoplexy is most commonly associated with pituitary adenoma. The common symptoms of pituitary apoplexy are severe headache with nausea and vomiting. Other symptoms depends upon the amount of hemorrhage and necrosis in the pituitary gland. Hemorrhage into the pituitary gland may compress the surrounding structures and present with ophthlamoplegia, cranial nerve palsies, and signs of increased intracranial pressure. The initial diagnostic test is a CT scan without contrast which will show the hemorrhage as a hyperintense lesion. In the case of inconclusive CT, an MRI may be done to better visualize the lesion. Laboratory tests are done to identify specific hormone and electrolyte disturbances. The initial management of pituitary apoplexy includes rapid hemodynamic stabilization of the patient with replacement of hormones. Depending upon the patient’s condition after initial management, neurological decompression may be done.^[1][2]

Pituitary apoplexy was first discovered by Pearce Bailey in the year 1898. In 1905, Leopold Bleibtreu recorded the postmortem examination of a 21-year-old acromegalic patient, in whom he discovered that the pituitary gland had been replaced by an old hemorrhage. The term “pituitary apoplexy” was coined by Brougham, Heusner, and Adams in the year 1950.^[3]

Pituitary apoplexy is an acute clinical syndrome caused by hemorrhage and necrosis in the pituitary gland. Most commonly, pituitary apoplexy is associated with pituitary adenoma. The pituitary adenoma predisposes the patient to an increased risk of bleeding within the pituitary gland. The pituitary adenoma has fenestrated endothelium surrounded by a variable number of smooth muscle cells, which are not found in the normal pituitary gland.Gene involved in the pathogenesis of pituitary apoplexy include a mutation in AIP gene, which is located on chromosome 11q13.2. On gross pathology, pituitary apoplexy presents with hemorrhage with or without necrosis. Electron microscopic shows evidence of abnormal fenestration of tumor vessels (pituitary adenoma) with fragmented basal membranes that may predispose the patient to hemorrhage.

Pituitary apoplexy must be differentiated from other diseases that cause severe headache such as subarachnoid hemorrhage, meningitis, intracranial mass, cerebral hemorrhage, cerebral infarction, intracranial venous thrombosis, migraine, head injury, lymphocytic hypophysitis, and radiation injury.^[4][5][6]

The worldwide prevalence of pituitary apoplexy is 6.2 per 100,000 persons. The incidence of pituitary apoplexy is 0.7 per 100,000 persons.^[7]

Common risk factors in the development of pituitary apoplexy include bleeding disorders, diabetes, use of a breathing machine, radiation to the pituitary gland, angiography, head injury, surgery, pituitary stimulation, and pregnancy induced lactotroph hyperplasia.^[8]

There are no screening guidelines for pituitary apoplexy.

If left untreated, pituitary apoplexy is an acute life threatening condition. Pituitary apoplexy may lead to a sudden decline in pituitary hormone production. The most life threatening endocrinopathy is acute adrenal crisis. Complications of pituitary apoplexy include vision loss, optic neuritis, diplopia, ptosis, increased intracranial pressure, hypothyroidism, hypogonadism, and growth hormone deficiency. The prognosis of pituitary apoplexy depends upon presentation and initiation of therapy. Emergent application of medical and surgical treatment is associated with greater improvement in visual field defects, visual acuity, and diplopia. The outlook is good for people who are diagnosed early and treated. Patients require hormone(s) replacement therapy for life.^[9]

Pituitary apoplexy usually has a short period of symptoms (acute). Symptoms usually include severe headache, paralysis of eye muscles, visual disturbances, nausea, and vomiting.^[10]

Patients with pituitary apoplexy appear ill and usually look tired. Physical examination of patients with pituitary apoplexy is usually remarkable for orthostatic hypotension, visual acuity and visual field defects, cranial nerve palsies, Horner syndrome, meningeal irritation, altered level of consciousness, severe mental status change, and other signs of hypopituitarism.

Laboratory findings consistent with the diagnosis of pituitary apoplexy include endocrinopathies from hypofunction of the pituitary gland. Blood tests will be done to check levels of ACTH, cholesterol, cortisol, growth hormone, LH, prolactin and somatomedin C (IGF-1).

X-ray is an inexpensive method for evaluating pituitary apoplexy. However, x-ray is neither the best initial test, nor the most accurate test in evaluating pituitary apoplexy.

CT scan without contrast is the initial test of choice in emergency department patients who present with sudden-onset severe headache, visual loss or ophthalmoplegia suggestive of pituitary apoplexy. A CT scan can also help to differentiate whether subarachnoid hemorrhage is arising from pituitary hemorrhage or an aneurysm.

MRI is done if the CT scan is suspicious for pituitary apoplexy. MRI is more sensitive than CT scan. MRI is more accurate in distinguishing the soft tissues of the pituitary from the surrounding bony structures. MRI is also superior to CT scan for detecting ischemia and infarction in brain tissue.

There are no ultrasound findings associated with pituitary apoplexy.

There are no other imaging findings associated with pituitary apoplexy.

There are no other diagnostic studies associated with pituitary apoplexy.

The optimal therapy for pituitary apoplexy depends upon presentation of the patient. The emphasis is on early hemodynamic stabilization of the patient, with evaluation for signs of deficiency of pituitary hormones. Life threatening hypopituitarism must be treated with replacement of hormones.

Neurological decompression is done once the patient is hemodynamically stable. Surgery relieves pressure on the pituitary and improves visual field defects and ocular palsy. Early decompression has been associated with better visual and endocrine outcome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Pituitary apoplexy was first discovered by Pearce Bailey in the year 1898. In 1905, Leopold Bleibtreu recorded the postmortem examination of a 21-year-old acromegalic patient, in whom he discovered that the pituitary gland had been replaced by an old hemorrhage. The term pituitary apoplexy was coined by Brougham, Heusner, and Adams in 1950.

• In 1898, Pearce Bailey, an American neurologist, discovered pituitary apoplexy.
• In 1905, Leopold Bleibtreu, a German physicist, performed the first postmortem examination on a patient with pituitary apoplexy.
• In 1950, Brougham, Heusner, and Adams from the Boston City Hospital and Harvard Medical School coined the term “pituitary apoplexy”.^[1]

• In 1925, the first surgery for pituitary apoplexy was performed.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Pituitary apoplexy is an acute clinical syndrome caused by hemorrhage and necrosis in the pituitary gland. Most commonly, pituitary apoplexy is associated with pituitary adenoma. Pituitary adenoma predisposes the patient to an increased risk of bleeding within the pituitary gland. Pituitary adenoma has fenestrated endothelium surrounded by a variable number of smooth muscle cells which are not found in the normal pituitary gland, leading to increased susceptibility to pituitary apoplexy in these tumors. Pituitary apoplexy can result from a mutation in AIP gene which is a tumor suppressor gene located on chromosome 11q13.2. On gross pathology, pituitary apoplexy presents with hemorrhage with or without necrosis. Electron microscopy shows evidence of abnormal fenestration of tumor vessels (pituitary adenoma) with fragmented basal membranes that may predispose the patient to hemorrhage.

Pituitary apoplexy is caused by bleeding into the pituitary gland. Most often, pituitary apoplexy is seen with a pituitary adenoma. Pituitary adenoma predisposes the patient to an increased risk of bleeding within the pituitary gland.^{[1][2][3][4][5][6][7][8]}

• Pituitary adenomas have decreased blood supply and angiogenesis.
• A pituitary adenoma has fenestrated endothelium surrounded by a variable number of smooth muscle cells, which are not found in the normal pituitary gland.

• VEGF mRNA may be increased in pituitary tumors, especially in non-functioning pituitary adenomas, which could be related to an abnormal vascularity.

• Enlarging pituitary adenomas may outgrow their blood supply, making them susceptible to bleeding and infarction.

• The bleeding may lead to increase in intrasellar pressure. The increased intrasellar pressure may compress the adjoining structures and lead to the clinical symptoms of pituitary apoplexy.
  • An enlarged pituitary tumor may become impacted at the diaphragmatic notch, leading to compression of the hypophyseal stalk and its vascular supply.
  • This may render the anterior pituitary gland and its tumor with reduced blood supply causing ischemia and subsequent necrosis.
  • Reperfusion after infarction may lead to hemorrhage within the pituitary gland or adenoma.

• Gene involved in the pathogenesis of pituitary apoplexy include a mutation in AIP gene, which is located on chromosome 11q13.2.
• The most common mutation site in the AIP gene is p.R304 locus.
• Mutated AIP loses its activity as a tumor suppressor gene and leads to increased cell proliferation.
• The penetration of AIP positive carriers is 12-30%.

Pituitary apoplexy is seen with 0.6 to 10% of pituitary adenomas.

• The predominant finding is hemorrhage with or without necrosis.
• Pale, necrotic material is particularly found when there is a long interval between the acute clinical event and surgery.

Electron microscopic shows evidence of abnormal fenestration of tumor vessels (pituitary adenoma) with fragmented basal membranes that may predispose the patient to hemorrhage.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Pituitary apoplexy is most commonly caused by bleeding into the pituitary gland from a benign tumor of the pituitary. When this bleeding occurs in a woman during or immediately after childbirth, it is called Sheehan syndrome. Other conditions causing pituitary apoplexy are coagulopathy, major surgery, hypertension, drugs such as dopamine receptor agonists, GnRH agonists, antiplatelets, and thrombolytic therapy.

The most common cause of pituitary apoplexy is pituitary adenoma (a benign tumor of pituitary gland). Other common causes include:^[1][2][3][4]

• Coagulopathy
• Surgery predisposing to hypotension
• Systemic hypertension
• Drugs causing pituitary apoplexy:
  • Antiplatelet therapy
  • Thrombolytic therapy
  • Dopamine receptor agonists
  • GnRH agonists
  • Estrogen replacement therapy
• Pregnancy and post-partum
• Hormonal stimulation of pituitary with TRH, GnRH and CRH

• Head injury
• Radiation therapy
• Pituitary surgery

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Pituitary apoplexy must be differentiated from other diseases that cause severe headache such as subarachnoid hemorrhage, meningitis, intracranial mass, cerebral hemorrhage, cerebral infarction, intracranial venous thrombosis, migraine, head injury, and lymphocytic hypophysitis.

Pituitary apoplexy should be differentiated from other diseases causing severe headache for example: ^{[1][2][3][4][5][6][7][8][9][10][11]}

Pituitary apoplexy should be differentiated from other diseases causing hypopituitarism.^{[10][12][13][14][15][16][17]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

The worldwide prevalence of pituitary apoplexy is 6.2 per 100,000 persons. The incidence of pituitary apoplexy is 0.7 per 100,000 persons.^[1]

• Worldwide, the prevalence of pituitary apoplexy is 6.2 per 100,000 persons.^[1]

• Worldwide, the incidence of pituitary apoplexy is 0.7 per 100,000 persons.^[2]

• Pituitary apoplexy is commonly seen in adults with a mean age of 57 years.

• Males are more commonly affected with pituitary apoplexy than females. Two-thirds of all patients are male.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

Common risk factors in the development of pituitary apoplexy include bleeding disorders, diabetes, use of a breathing machine, radiation to the pituitary gland, angiography, head injury, surgery, pituitary stimulation, and pregnancy induced lactotroph hyperplasia.

Common risk factors in the development of pituitary apoplexy include:^[1][2]

• Bleeding disorders
• Diabetes
• Use of a breathing machine
• Radiation to the pituitary gland
• Angiography
• Head injury
• Surgery leading to hypotension
• Pituitary stimulation with ACTH, TRH or GnRH analogue
• Pregnancy induced lactotroph hyperplasia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Akshun Kalia M.B.B.S.[2]

If left untreated, pituitary apoplexy can be an acute life threatening condition. Pituitary apoplexy may lead to a sudden decline in pituitary hormone production. The most life threatening endocrinopathy is an acute adrenal crisis. Complications of pituitary apoplexy include vision loss, optic neuritis, diplopia, ptosis, increased intracranial pressure, hypothyroidism, hypogonadism, and growth hormone deficiency. The prognosis of pituitary apoplexy depends upon presentation and initiation of therapy. Emergent application of medical and surgical treatment is associated with greater improvement in visual field defects, visual acuity, and diplopia. The outlook is good for people who are diagnosed early and treated. Patients require hormone(s) replacement therapy for life.

If left untreated, pituitary apoplexy features depend upon the size of hemorrhage. Pituitary apoplexy is an acute life threatening condition in case of massive hemorrhage. Pituitary apoplexy may lead to a sudden decline in pituitary hormone production. The most life threatening endocrinopathy is an acute adrenal crisis. In a case of small sized hemorrhage, pituitary apoplexy may result in some temporary or permanent endocrinopathies from hypofunction of the pituitary gland.^[1][2]

Complications of pituitary apoplexy can include:

• Adrenal crisis
• Vision loss and optic neuritis
• Diplopia
• Ptosis
• Increased intracranial pressure
• Hypothyroidism
• Hypogonadism
• Growth hormone deficiency

• Acute pituitary apoplexy can be life-threatening.
• The mortality rate associated with pituitary apoplexy is 12.5% and without treatment, the mortality rate can reach as high as 50%.
• Emergent application of medical and surgical treatment is associated with greater improvement in visual field defects, visual acuity, and diplopia.
• Prognosis is good for people who are diagnosed early and treated. Patients require hormone(s) replacement therapy for life.^[3][4][5][6]

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