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Pituitary Apoplexy


Pituitary Apoplexy

Article Author:
Miguel Mayol Del Valle
Article Editor:
Orlando De Jesus
Updated:
8/11/2020 11:35:51 AM
For CME on this topic:
Pituitary Apoplexy CME
PubMed Link:
Pituitary Apoplexy

Introduction

Pituitary apoplexy is a condition in which there is a hemorrhage or infarction of the pituitary gland. This disorder usually occurs in a pre-existing pituitary adenoma.[1][2][3] The term pituitary apoplexy or apoplexia refers to the "sudden death" of the pituitary gland, usually caused by an acute ischemic infarction or hemorrhage. Pearce Bailey described the first case of pituitary tumor-associated hemorrhage in 1898, but the term pituitary apoplexy referring to both necrosis and bleeding into pituitary tumors was first used in 1950 by Brougham et al.[4] Pituitary apoplexy is a medical and surgical emergency in many cases. Prompt identification and evaluation are imperative to improve outcomes.

Etiology

A pre-existing pituitary adenoma is usually found in cases of pituitary apoplexy. In the majority of the cases, the patients are unaware of the tumor.[5] Several predisposing or contributing factors for pituitary apoplexy include endocrine stimulation tests,[6] bromocriptine or cabergoline treatment,[7][8] gonadotropin-releasing hormone treatment,[9] lumbar fusion in the prone position,[10][11] pregnancy,[12][13] pituitary irradiation,[14] anticoagulation,[15] thrombocytopenia,[16][17] and erectile dysfunction medications.[18]

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.

Epidemiology

The reported incidence of pituitary apoplexy varies significantly from 1.5-27.7% in cases of pituitary adenoma, but many of them do not distinguish between symptomatic and asymptomatic patients. When symptomatic cases only are included, the incidence approaches 10%.[2][19][20][21] If non-symptomatic intratumoral hemorrhage detected by neuroimaging studies is considered, the incidence increases to 26%. Apoplexy in pituitary adenomas is rare and is estimated at 0.2% annually. Tumors larger than 10 cm have a higher risk, and those in which rapid growth has been documented.[22]

Most patients fall in the age range of 37-58 years.[23] There is a male-to-female ratio approaching 2:1.[21][23][24]

Pathophysiology

Hemorrhage produces an acute expansion of the tumor, which produces many of the symptoms. Visual symptoms are caused by direct compression of the optic nerves or chiasm, and hormonal dysfunction is caused by the sudden interruption of the release of the hormones. 

Several theories had been proposed to explain the ischemic and hemorrhagic changes found in the tumor and the normal gland. Although they are proposed as separate mechanisms, probably each theory contributes to some process, and the combination of them is what ultimately produces the apoplexy. One theory postulates that the compression of the superior hypophyseal artery and its branches against the diaphragma sella leads to ischemia of the anterior pituitary gland and the tumor.[2][3][25] Another theory proposes that the thin pituitary vascular network is compressed as it is located inside the small intrasellar compartment causing ischemia, necrosis, and hemorrhage.[2][3][26] Lastly, another theory stipulates that the rapid expansion of the tumor outstrips its vascular supply, resulting in ischemia and necrosis.[2][3][27]

History and Physical

A sudden-onset headache located behind the eyes is the most common symptom.[3][28] Several mechanisms have been postulated 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.

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 apoplexy. The lack of secretion causes a cessation of cortisol secretion by the adrenal gland, which produces a variety of symptoms called "adrenal crisis."[2][3] The patient may have nausea and vomiting, abdominal pain, bradycardia and hypotension, hypothermia, lethargy, and sometimes coma.

Evaluation

Computed tomographic (CT) scan: Non-contrast head CT scan is usually performed first as it is easier to obtain. It will show a sellar/suprasellar mass associated with intralesional hemorrhage. Ischemia or necrosis of the gland/tumor can not be identified. Contrast examination is done afterward to delimit the size of the tumor as the hemorrhagic products, and contrast-enhancing areas are hyperdense to the brain.

Magnetic resonance imaging (MRI): Brain MRI is performed to improve the definition of the lesion. MRI is the diagnostic imaging modality of choice.[2][23] It can easily identify hemorrhagic and necrotic areas. The characteristic brain MRI finding in an ischemic pituitary apoplexy is an enlarged sellar/suprasellar mass with peripheral enhancement surrounding a hypointense center. Diffusion-weighted imaging provides information about the consistency of the tumor and is very useful to identify ischemic tissue after arterial occlusion has occurred.[2] For a hemorrhagic apoplexy, T1-weighted MRI shows a sellar/suprasellar lesion with intralesional areas of high signal intensity, suggesting the presence of blood.[3] The MRI gradient-echo sequence T2-star weighted (T2*W), is very sensitive to detect deposits of hemosiderin.[2]

Hormonal evaluation: Pituitary hormonal evaluation is required, as nearly 80% of patients present with a deficiency of at least one of the anterior pituitary hormones.[1] The most common deficiencies are growth hormone deficit in 90% of the patients and ACTH deficit in 70% of them.[2][32]

Grading system: A 5-grade classification based on the clinical presentation spectrum had been recently proposed for treatment decisions and outcomes.[33]

Treatment / 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.[32] All patients should receive corticosteroids even if they do not present symptoms of adrenal crisis. 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.[3]

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. Emergency surgery should be reserved for patients with progressive deterioration of consciousness, hypothalamic involvement, and progressive visual worsening. It has been demonstrated that a significant postoperative clinical improvement is a consequence of a surgical procedure performed as soon as possible.[23] 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.[34][35] 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.[30][36][37] 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.[38] 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. 

Pediatric pituitary tumor apoplexy has a more aggressive natural history in comparison to adults, and early surgery may reduce its occurrence and improve outcomes.[39][40]

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[41][42][43]
  • Temporal arteritis[44]
  • Aneurysm
  • Craniopharyngioma
  • Subarachnoid hemorrhage[45]
  • Meningitis,[46] encephalitis 
  • Cavernous sinus thrombosis
  • Basilar artery infarct
  • Hypertensive encephalopathy
  • Ophthalmoplegic migraine[47]
  • Retrobulbar neuritis

Prognosis

Pituitary apoplexy can be a life-threatening condition if not detected and treated. The overall mortality is 1.6% to 1.9%.

Visual acuity, visual field defects, and ophthalmoplegia improve in the majority of the patients after both conservative and surgical decompression. 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. Although visual outcome appears to be better with early intervention as compared to late,[48] 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.[49] A complete restoration of the oculomotor palsy usually needs 3 months, while abducens nerve palsy usually needs 6 months.[23] 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.[30]

Gross total resection and short duration of preoperative headaches are predictors for improvement in postoperative headaches.[50] Hormonal replacement therapy is needed in 80% of the patients.[1][21][49] In some cases that are treated conservatively, spontaneous remission of the tumor has occurred, and surgery is not required.[51][52] This may be caused by ischemic necrosis of the tumoral tissue.

Complications

  • Visual loss
  • Adrenal crisis
  • Ophthalmoplegia
  • Increased intracranial pressure
  • Ptosis
  • Diabetes insipidus
  • Bilateral cerebral infarcts[53][54][55]

Consultations

  • Neurosurgery
  • Hospitalist
  • Ophthalmology
  • Endocrinology

Deterrence and Patient Education

Patients with pituitary apoplexy may have a long residual endocrine deficiency and should have an assessment of pituitary function at 4 to 8 weeks after the event. Assessment of visual acuity, eye movements, and visual fields is mandatory. An MRI scan is recommended at 3 to 6 months after an episode to evaluate for residual tumor, and thereafter an annual MRI scan should be considered for the next 5 years.

Those patients with a known tumor should be educated about the possibility of hemorrhage. They should be encouraged to attend their endocrinologist and neurosurgeon scheduled visits. Any acute visual change or significant headache should alert them to seek immediate medical evaluation.

Enhancing Healthcare Team Outcomes

Pituitary apoplexy frequently poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as headache, vomiting, and nausea. Sometimes, visual problems alert the patient of a more serious problem. The diagnosis is difficult to recognize without proper imaging studies.

While the neurosurgeon is almost always involved in the care of patients with pituitary apoplexy, it is important to consult with an interprofessional team of specialists that include an endocrinologist and ophthalmologist. The nurses are also vital members of the interprofessional team as they will monitor the patient's vital signs and assist with the education of the patient and family. Those patients with adrenal crisis have to be monitored in an intensive care unit until hemodynamically stable. In the postoperative period for pain, wound infection prophylaxis, and hormonal replacement, the pharmacist will ensure that the patient is on the right analgesics, hormonal replacements, and appropriate antibiotics. The neuroradiologist also plays a vital role in determining if pituitary apoplexy is secondary to hemorrhage or ischemia. Without providing a proper history, the neuroradiologist may not be sure what to look for or what additional radiologic exams may be needed.



(Click Image to Enlarge)
MR Head Sag T1 Pituitary Apoplexy
MR Head Sag T1 Pituitary Apoplexy
Contributed by Scott Dulebohn, MD

References

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