Pituitary Apoplexy

Back

Background

The word apoplexy is defined as a sudden neurologic impairment, usually due to a vascular process. 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. An existing pituitary adenoma is usually present. The visual symptoms may include both visual acuity impairment and visual field impairment from involvement of the optic nerve or chiasm and ocular motility dysfunction from involvement of the cranial nerves traversing the cavernous sinus.[1] It is important to note that pituitary apoplexy may be divided into hemorrhagic or ischemic, each with unique neuroimaging findings.

See the image below.



View Image

Enhanced T1-weighted axial and coronal MRI showing a large pituitary tumor that has recently undergone ischemic apoplexy showing a necrotic (hypointen....

Pathophysiology

Pituitary apoplexy stems from an acute expansion of a pituitary adenoma or, less commonly, in a nonadenomatous gland, from infarction or hemorrhage. 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.

Some postulate that a gradual enlarging pituitary tumor becomes impacted at the diaphragmatic notch, compressing and distorting the hypophyseal stalk and its vascular supply. 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. This explanation is doubtful, since most tumors that undergo apoplexy are slow growing.

Epidemiology

Frequency

International

Pituitary apoplexy results in an estimated 1.5-27.7% of cases of pituitary adenoma, although the figure is probably closer to 10%.

Mohr and Hardy reviewed hospital records of 664 patients who had surgery for pituitary adenomas.[2] They noted typical symptomatic pituitary apoplexy to occur in only 0.6% of patients with significant hemorrhagic and necrotic changes in 9.5% of surgical specimens.

Frequency of intratumoral hemorrhage increases to 26% if using only MRI criteria without clinical evidence of apoplexy. However, hemorrhagic pituitary apoplexy may be fatal. Kurisu et al reported a 68-year-old man who developed pituitary apoplexy resulting in massive intracerebral hemorrhage and death 1 month later.[3]

Sex

Pituitary apoplexy has a male-to-female ratio of 2:1.

Age

The usual age range is 37-57 years. Pediatric pituitary apoplexy has been described.[4]

Prognosis

Pituitary apoplexy can be a life-threatening condition, which is not easily diagnosed or treated. When appropriately managed, visual symptoms often improve, but endocrinologic function may remain compromised.[5]

Patient Education

Educate patients about the disorder and the complications that can arise from the treatment of the disorder.

History

Patients with pituitary apoplexy may present with the following complaints[6] :

There is one case report of recalcitrant hiccups in association with pituitary apoplexy.[7]

Physical

Clinical presentation is marked by headache in 95% of cases. The headache is sudden and postulated to result from stretching and irritation of the dura mater in the walls of the sella supplied by the meningeal branches of cranial nerve V. The headache also may result from irritation of the trigeminal nerve from the expanding mass. Frequently, it is retro-orbital in location and may be unilateral at onset, then becomes generalized.

Vomiting occurs in 69% of patients and often accompanies the headache. The mechanism is unclear but may be due to meningeal irritation or increased intracranial pressure.

Visual acuity defects (52%) and visual field defects (64%) result from upward expansion of the tumor, which compresses the optic chiasm, optic tracts, or optic nerve. The classic visual field defect is a bitemporal superior quadrantic defect. Optic tract involvement from a prefixed chiasm is less common and results in a contralateral homonymous hemianopia. Optic nerve compression from a postfixed chiasm is rare and may mimic optic neuritis with pain on eye movement, monocular visual acuity loss, and a central scotoma on visual field testing. See the image below.



View Image

Automated visual field showing a bitemporal field defect due to compression of the optic chiasm from below.

Ocular paresis (78%) results from compression of the cavernous sinus, which makes cranial nerves III, IV, and VI vulnerable to compression. If consciousness is maintained, diplopia may be present. Of the cranial nerves, the oculomotor nerve (cranial nerve III) is involved most commonly, resulting in a unilateral dilated pupil, ptosis, and a globe that is deviated inferiorly and laterally.[8]

Less commonly, cranial nerve IV is involved. A fourth cranial nerve palsy typically manifests as vertical diplopia that worsens when the patient gazes in a direction opposite or tilts the head toward the direction of the hypertropic (affected) eye. It also is worsened by downgaze.

Cranial nerve VI is least commonly involved, perhaps because, in the cavernous sinus, it is more sheltered from the pituitary expansion than are cranial nerves III and IV. Abducens involvement produces horizontal diplopia owing to the inability to abduct the involved eye.

Trigeminal nerve (cranial nerve V) involvement may produce facial pain or sensory loss.

Horner syndrome may develop from damage to the sympathetic fibers. Hemispheric deficits may also develop.

The carotid siphon may be compressed against the anterior clinoid process, leading to stroke and vasospasm from subarachnoid blood.

Leakage of blood and necrotic tissue into the subarachnoid space may lead to meningismus, stupor, and coma.

The cerebrospinal fluid frequently is marked by increased pressure and pleocytosis (even in the absence of hemorrhage), increased numbers of red blood cells, and xanthochromia.

Involvement of the hypothalamus may alter thermal regulation. Destruction of adenohypophyseal tissue may lead to endocrinologic deficiencies.

Rarely, pituitary apoplexy can occur in ectopic sites. Hori examined normal adult brains at autopsy and found ectopic pituitary cells in the leptomeninges of the peri-infundibular region in 75%.[9] He postulated that these cells may produce an ectopic pituitary adenoma. Ectopic pituitary adenomas commonly present late because they displace rather than invade vital nervous structures. They may be discovered only after the patient has pituitary apoplexy. Only one case of an ectopic pituitary adenoma that underwent apoplexy has been reported.

Causes

Predisposing factors of pituitary apoplexy include endocrine stimulation tests, bromocriptine treatment, head trauma, pregnancy, pituitary irradiation, and, perhaps, anticoagulation.[10]

Okuda reported one woman with a giant pituitary adenoma who underwent triple bolus stimulation test with luteinizing hormone-releasing hormone, thyrotropin-releasing hormone (THR), and insulin.[11] 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.

Some associate apoplexy with administration of gonadotrophin-releasing hormone. Corticotropin-releasing hormone 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 during induction chemotherapy for acute myeloid leukemia has been reported by Silberstein and colleagues.[12]

Apoplexy has been reported after cardiac bypass surgery by Thurtell and colleagues.[13]

Brar and Garg reported a case of pituitary apoplexy in a young man who ascended to high altitude gradually, even after proper acclimatization.[14]

Pituitary apoplexy has been reported in a patient with dengue fever and thrombocytopenia.[15] Kruljac et al reported a patient with pituitary metastasis presenting as ischemic pituitary apoplexy following heparin-induced thrombocytopenia.[16]

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.

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. 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. Notwithstanding, Sheehan syndrome is regarded as a neurological emergency and is potentially lethal.

In Sheehan syndrome, lactation failure may occur result from 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 to 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" (see Imaging Studies).[17]

Weisberg warns that radiotherapy is potentially hazardous in pituitary tumors with prior hemorrhagic, necrotic, or cystic changes.[18] Apoplexy may be precipitated in these cases.

Some believe that 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.[19] Both may result in brain ischemia.

Complications

Complications include optic neuritis, acute ophthalmoplegia, increased intracranial pressure, extraocular muscle paralysis, and ptosis.

Frontal lobe herniation and chiasmal herniation have been reported.[20]

Laboratory Studies

At least one anterior pituitary deficiency is always present at the onset of pituitary apoplexy, with corticotropic deficiency being the most common and most life-threatening, affecting 60%-80% of patients.[24] Electrolytes, glucose, pituitary hormones, and plasma/urine osmolality should be evaluated.

Imaging Studies

CT scanning and MRI are radiologic tests used to evaluate the pituitary.

CT scanning is generally 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 SAH. CT scanning can help to exclude SAH from an aneurysm by showing an intrasellar mass with hemorrhagic components, seen in 80% of pituitary apoplexy cases.[24]

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.[25]

Kaplun and colleagues reported the MRI evolution of pituitary changes in 2 patients with Sheehan syndrome.[26] The first case initially had the pituitary ring sign, although MRI later showed an empty sella with shrinkage of the pituitary.

Liu et al 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).[27]

MRI, as seen in the images below, is the most sensitive imaging study for evaluating the pituitary gland, possibly visualizing hemorrhage not seen on CT scan.



View Image

Enhanced axial and coronal T1-weighted MRI of a typical large pituitary tumor with a "snowman" configuration (coronal) and marked enhancement with con....



View Image

Enhanced T1-weighted axial and coronal MRI showing a large pituitary tumor that has recently undergone ischemic apoplexy showing a necrotic (hypointen....

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.[17] Vaphiades retrospectively reviewed the cranial MRIs of 3 patients with ischemic (nonhemorrhagic) pituitary apoplexy; all 3 patients displayed the "pituitary ring sign."[17]

This MRI appearance of the “pituitary ring” was first noted in 1995 by Lavalee et al in a patient with Sheehan syndrome on a contrast-enhanced CT scan and on a T1-weighted contrast-enhanced MRI and thought to be unique to ischemic apoplexy in patients with Sheehan syndrome.[28]

In 1998, Kleinschmidt-Demasters and Lillehei reported the pathological and MRI features of 15 patients with pituitary adenomas presenting with apoplexy. On T1-weighted contrast-enhanced MRI, they observed a peripheral rim of enhancement with gadolinium in 10 cases.[29]

Subsequent reports corroborated this MRI finding in patients with ischemic pituitary apoplexy.[30, 31]

The presumed etiology of the hypointense center in the pituitary gland is necrosis, which does not enhance with gadolinium on T1-weighted MRI. The enhancing part of the tumor is the outer-most portion of the infarcted pituitary or its “skin.” This was found to correspond to the presence of granulation tissue and lymphocytosis at histologic examination.[29]

Sphenoid sinus mucosal thickening in the setting of pituitary apoplexy was first described by Arita et al in 2001. 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 when performed within 7 days after the onset of apoplectic symptoms. Controls consisted of MRIs obtained in 100 consecutive patients with pituitary adenomas but without apoplectic symptoms. Included in this group were 58 functioning and 42 nonfunctioning pituitary adenomas. Fifteen patients experienced thickening of the sphenoid sinus mucosa, including 5 with some apparent pansinusitis. The incidence of mucosal thickening of the sphenoid sinus in patients with apoplexy was significantly greater than that in the patients without apoplexy.[32] On histopathological specimens in patents with apoplexy, the thickened sphenoid sinus mucosa demonstrates a swollen subepithelial layer presumably responsible for the rim of MRI gadolinium enhancement.[32]

In 2006, Liu et al performed a retrospective review of 28 patients with pituitary apoplexy. Thickening of sphenoid sinus mucosa was found in 22 (79%) of these patients. They also noted that patients with thickened sphenoid sinus mucosa had larger tumors, 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 to patients without thickened mucosa.[33]

In 2011, Agrawal et al 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.[34]

In 2017, Vaphiades reviewed twelve cases of ischemic pituitary apoplexy, all of which showed both the "pituitary ring sign" and "sphenoid sinus mucosal thickening" signs on MRI. The twelve cases were composed of ten cases from the literature (3 of which were published by this author) and two cases recently evaluated in the author’s hospital. Thus, five of the twelve cases were evaluated by this author. Five of the twelve patients had both headache and visual loss, five had headache alone, and two had no initial symptoms (nonfunctioning pituitary adenomas were incidentally found on MRI). These findings indicate that each sign ("pituitary ring sign" and "sphenoid sinus mucosal thickening") may exist alone with or without pituitary apoplexy, yet both signs together in the appropriate clinical context is a strong predictor of pituitary apoplexy. This is important because timely diagnosis treatment of pituitary apoplexy may be vision- and life-saving in this disorder.[35] See image below.



View Image

Post-contrast sagittal T1-weighted scan shows sphenoid sinus roof mucosal thickening. The yellow arrow shows the “pituitary ring sign,” while the whit....

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

Medical 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).[24]

Medical treatment consists of the following:

Surgical Care

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.[38, 39, 24]

Consultations

See the list below:

Further Inpatient Care

Monitor metabolic status, visual acuity, visual fields, and ocular motility.

Medication Summary

As corticotropic deficiency is present in most patients with pituitary apoplexy and may be life-threatening,[24] the goals of pharmacotherapy are to correct the corticosteroid deficiency, to reduce morbidity, and to prevent complications.

Hydrocortisone (Hydrocortone, Cortef, Solu-Cortef)

Clinical Context:  Hydrocortisone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Corticosteroids replenish the cortisol that would normally be produced under this type of physiologic stressful situation.

What is pituitary apoplexy?What is the pathophysiology of pituitary apoplexy?What is the global prevalence of pituitary apoplexy?What are the sexual predilections of pituitary apoplexy?Which age groups have the highest prevalence of pituitary apoplexy?What is the prognosis of pituitary apoplexy?What is included in patient education about pituitary apoplexy?What are the signs and symptoms of pituitary apoplexy?Which physical findings are characteristic of pituitary apoplexy?What causes pituitary apoplexy?What are the possible complications of pituitary apoplexy?Which conditions are included in the differential diagnoses of pituitary apoplexy?What are the differential diagnoses for Pituitary Apoplexy?Which lab tests are performed in the workup of pituitary apoplexy?What is the role of imaging studies in the workup of pituitary apoplexy?Which histologic findings are characteristic of pituitary apoplexy?How is pituitary apoplexy treated?What is the role of surgery in the treatment of pituitary apoplexy?Which specialist consultations are beneficial to patients with pituitary apoplexy?What is included in the inpatient care of pituitary apoplexy?What is the role of medications in the treatment of pituitary apoplexy?Which medications in the drug class Corticosteroids are used in the treatment of Pituitary Apoplexy?

Author

Michael S Vaphiades, DO, Professor, Departments of Ophthalmology, Neurology, and Neurosurgery, Chief of Neuro-Ophthalmology and Electrophysiology Services, University of Alabama at Birmingham School of Medicine; Consulting Staff, Children's Hospital, Birmingham

Disclosure: Nothing to disclose.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Edsel Ing, MD, MPH, FRCSC, Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Active Staff, Michael Garron Hospital (Toronto East Health Network); Consulting Staff, Hospital for Sick Children and Sunnybrook Hospital, Canada

Disclosure: Nothing to disclose.

Acknowledgements

Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

References

  1. Nawar RN, AbdelMannan D, Selman WR, Arafah BM. Pituitary tumor apoplexy: a review. J Intensive Care Med. 2008 Mar-Apr. 23(2):75-90. [View Abstract]
  2. Mohr G, Hardy J. Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol. 1982 Sep. 18(3):181-9. [View Abstract]
  3. Kurisu K, Kawabori M, Niiya Y, Ohta Y, Mabuchi S, Houkin K. Pituitary apoplexy manifesting as massive intracerebral hemorrhage. Case report. Neurol Med Chir (Tokyo). 2012. 52(8):587-90. [View Abstract]
  4. Culpin E, Crank M, Igra M, Connolly DJA, Dimitri P, Mirza S, et al. Pituitary tumour apoplexy within prolactinomas in children: a more aggressive condition?. Pituitary. 2018 Oct. 21 (5):474-479. [View Abstract]
  5. Giritharan S, Gnanalingham K, Kearney T. Pituitary apoplexy - bespoke patient management allows good clinical outcome. Clin Endocrinol (Oxf). 2016 Sep. 85 (3):415-22. [View Abstract]
  6. Mou C, Han T, Zhao H, Wang S, Qu Y. Clinical features and immunohistochemical changes of pituitary apoplexy. J Clin Neurosci. 2009 Jan. 16(1):64-8. [View Abstract]
  7. Simsek Bagir G, Civi S, Kardes O, Kayaselcuk F, Ertorer ME. Stubborn hiccups as a sign of massive apoplexy in a naive acromegaly patient with pituitary macroadenoma. Endocrinol Diabetes Metab Case Rep. 2017. 2017:[View Abstract]
  8. Bahmani Kashkouli M, Khalatbari MR, Yahyavi ST, Borghei-Razavi H, Soltan-Sanjari M. Pituitary apoplexy presenting as acute painful isolated unilateral third cranial nerve palsy. Arch Iran Med. 2008 Jul. 11(4):466-8. [View Abstract]
  9. Hori A. Suprasellar peri-infundibular ectopic adenohypophysis in fetal and adult brains. J Neurosurg. 1985 Jul. 63(1):113-5. [View Abstract]
  10. Ly S, Naman A, Chaufour-Higel B, Patey M, Arndt C, Delemer B, et al. Pituitary apoplexy and rivaroxaban. Pituitary. 2017 Aug 22. [View Abstract]
  11. Okuda O, Umezawa H, Miyaoka M. Pituitary apoplexy caused by endocrine stimulation tests: a case report. Surg Neurol. 1994 Jul. 42(1):19-22. [View Abstract]
  12. Silberstein L, Johnston C, Bhagat A, Tibi L, Harrison J. Pituitary apoplexy during induction chemotherapy for acute myeloid leukaemia. Br J Haematol. 2008 Oct. 143(2):151. [View Abstract]
  13. Thurtell MJ, Besser M, Halmagyi GM. Pituitary apoplexy causing isolated blindness after cardiac bypass surgery. Arch Ophthalmol. 2008 Apr. 126(4):576-8. [View Abstract]
  14. Brar KS, Garg MK. High altitude-induced pituitary apoplexy. Singapore Med J. 2012 Jun. 53(6):e117-9. [View Abstract]
  15. Kumar V, Kataria R, Mehta VS. Dengue hemorrhagic fever: A rare cause of pituitary tumor hemorrhage and reversible vision loss. Indian J Ophthalmol. Jul-Aug /2011. 59:311-2. [View Abstract]
  16. Kruljac I, Cerina V, Pecina HI, et al. Pituitary metastasis presenting as ischemic pituitary apoplexy following heparin-induced thrombocytopenia. Endocr Pathol. 2012 Dec. 23(4):264-7. [View Abstract]
  17. Vaphiades M. The "pituitary ring sign": An MRI sign of pituitary apoplexy. Neuro-ophthalmology. 2007. 31:111-6.
  18. Weisberg LA. Pituitary apoplexy. Association of degenerative change in pituitary ademona with radiotherapy and detection by cerebral computed tomography. Am J Med. 1977 Jul. 63(1):109-15. [View Abstract]
  19. Ahmed SK, Semple PL. Cerebral ischemia in pituitary apoplexy. Acta Neurochir. 2008. 150:1193-6.
  20. Pineyro MM, Furtenbach P, Lima R, Wajskopf S, Sgarbi N, Pisabarro R. Brain and Optic Chiasm Herniation into Sella after Pituitary Tumor Apoplexy. Front Endocrinol (Lausanne). 2017. 8:192. [View Abstract]
  21. Chokyu I, Tsuyuguchi N, Goto T, Chokyu K, Chokyu M, Ohata K. Pituitary apoplexy causing internal carotid artery occlusion--case report. Neurol Med Chir (Tokyo). 2011. 51:48-51. [View Abstract]
  22. Madhusudhan S, Madhusudhan TR, Haslett RS, Sinha A. Pituitary apoplexy following shoulder arthroplasty: a case report. J Med Case Rep. 2011 Jul 5. 5:284. [View Abstract]
  23. Mohindra S, Kovai P, Chhabra R. Fatal Bilateral ACA Territory Infarcts after Pituitary Apoplexy: A Case Report and Literature Review. Skull Base. 2010 Jul. 20(4):285-8. [View Abstract]
  24. Briet C, Salenave S, Chanson P. Pituitary Apoplexy. Endocrinol Metab Clin North Am. 2015 Mar. 44(1):199-209. [View Abstract]
  25. Binning MJ, Liu JK, Gannon BS, Osborn AG, Couldwell WT. Hemorrhagic and nonhemorrhagic Rathke cleft cysts mimicking pituitary apoplexy. J Neurosurg. 2008. 108:3-8.
  26. Kaplun J, Fratila C, Ferenczi A, Yang WC, Lantos G, Fleckman AM. Sequential pituitary MR imaging in Sheehan syndrome: report of 2 cases. AJNR Am J Neuroradiol. 2008 May. 29(5):941-3. [View Abstract]
  27. Liu S, Wang X, Liu YH, Mao Q. Spontaneous disappearance of the pituitary macroadenoma after apoplexy: a case report and review of the literature. Neurol India. 2012 Sep-Oct. 60(5):530-2. [View Abstract]
  28. Lavalee G, Morcos R, Palardy J, Aube M, Gilbert D. MR of nonhemorrhagic post-partum pituitary apoplexy. AJNR Am J Neuroradiol. 1995. 16:1939-41.
  29. Kleinschmidt-DeMasters BK, Lillehei KO. Pathological correlates of pituitary adenomas presenting with apoplexy. Hum Pathol. 1998 Nov. 29 (11):1255-65. [View Abstract]
  30. Vaphiades MS. The "pituitary ring sign": An MRI sign of pituitary apoplexy. Neuro-Ophthalmology. 2007. 31:111-6.
  31. Vaphiades MS, Simmons D, Archer RL, Stringer W. Sheehan syndrome: a splinter of the mind. Surv Ophthalmol. 2003 Mar-Apr. 48 (2):230-3. [View Abstract]
  32. Arita K, Kurisu K, Tominaga A, Sugiyama K, Ikawa F, Yoshioka H, et al. Thickening of sphenoid sinus mucosa during the acute stage of pituitary apoplexy. J Neurosurg. 2001 Nov. 95 (5):897-901. [View Abstract]
  33. Liu JK, Couldwell WT. Pituitary apoplexy in the magnetic resonance imaging era: clinical significance of sphenoid sinus mucosal thickening. J Neurosurg. 2006 Jun. 104 (6):892-8. [View Abstract]
  34. Agrawal B, Dziurzynski K, Salamat MS, Baskaya M. The temporal association of sphenoid sinus mucosal thickening on MR imaging with pituitary apoplexy. Turk Neurosurg. 2012. 22 (6):785-90. [View Abstract]
  35. Vaphiades MS. Pituitary Ring Sign Plus Sphenoid Sinus Mucosal Thickening: Neuroimaging Signs of Pituitary Apoplexy. Neuroophthalmology. 2017 Dec. 41 (6):306-309. [View Abstract]
  36. Bills DC, Meyer FB, Laws ER Jr, et al. A retrospective analysis of pituitary apoplexy. Neurosurgery. 1993 Oct. 33(4):602-8; discussion 608-9. [View Abstract]
  37. Kiyofuji S, Perry A, Graffeo CS, Giannini C, Link MJ. The dangers of the "Head Down" position in patients with untreated pituitary macroadenomas: case series and review of literature. Pituitary. 2018 Jun. 21 (3):231-237. [View Abstract]
  38. Thomason K, Macleod K, Eyres KS. Hyponatraemia after orthopaedic surgery - a case of pituitary apoplexy. Ann R Coll Surg Engl. 2009 Apr. 91(3):3-5. [View Abstract]
  39. Muthukumar N, Rossette D, Soundaram M, Senthilbabu S, Badrinarayanan T. Blindness following pituitary apoplexy: timing of surgery and neuro-ophthalmic outcome. J Clin Neurosci. 2008 Aug. 15(8):873-9. [View Abstract]
  40. Harrington DO, Drake NV. Chiasm. The Visual Fields, Text and Atlas of Clinical Perimetry. 1990. 290-6.
  41. Krisht AF, Tindall GT. Pituitary apoplexy. In: Clinical Decisions in Neuro-ophthalmology. 1999. 295-301.
  42. Rose-Innes AP. Sheehan syndrome. Gilman S, ed. Neurology Medlink. 2001.

Enhanced T1-weighted axial and coronal MRI showing a large pituitary tumor that has recently undergone ischemic apoplexy showing a necrotic (hypointense) center and ring of gadolinium enhancement (hyperintense), ie, the "pituitary ring sign." There is a small area of hemorrhagic blush in the center of the necrosis.

Automated visual field showing a bitemporal field defect due to compression of the optic chiasm from below.

Enhanced axial and coronal T1-weighted MRI of a typical large pituitary tumor with a "snowman" configuration (coronal) and marked enhancement with contrast. This tumor has not undergone apoplexy.

Enhanced T1-weighted axial and coronal MRI showing a large pituitary tumor that has recently undergone ischemic apoplexy showing a necrotic (hypointense) center and ring of gadolinium enhancement (hyperintense), ie, the "pituitary ring sign." There is a small area of hemorrhagic blush in the center of the necrosis.

Post-contrast sagittal T1-weighted scan shows sphenoid sinus roof mucosal thickening. The yellow arrow shows the “pituitary ring sign,” while the white arrow shows sphenoid sinus roof mucosal thickening. Courtesy of Taylor & Francis (Vaphiades MS. Pituitary Ring Sign Plus Sphenoid Sinus Mucosal Thickening: Neuroimaging Signs of Pituitary Apoplexy. Neuroophthalmology. 2017 Dec. 41 (6):306-309. Online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764063/.).

Enhanced coronal CT showing large pituitary tumor with a "snowman" configuration and heterogeneous density (mixed signal) within the tumor indicative of pituitary apoplexy. Hemorrhage was confirmed at surgery.

Enhanced axial and coronal T1-weighted MRI of a typical large pituitary tumor with a "snowman" configuration (coronal) and marked enhancement with contrast. This tumor has not undergone apoplexy.

Enhanced T1-weighted axial and coronal MRI showing a large pituitary tumor that has recently undergone ischemic apoplexy showing a necrotic (hypointense) center and ring of gadolinium enhancement (hyperintense), ie, the "pituitary ring sign." There is a small area of hemorrhagic blush in the center of the necrosis.

Automated visual field showing a bitemporal field defect due to compression of the optic chiasm from below.

Post-contrast sagittal T1-weighted scan shows sphenoid sinus roof mucosal thickening. The yellow arrow shows the “pituitary ring sign,” while the white arrow shows sphenoid sinus roof mucosal thickening. Courtesy of Taylor & Francis (Vaphiades MS. Pituitary Ring Sign Plus Sphenoid Sinus Mucosal Thickening: Neuroimaging Signs of Pituitary Apoplexy. Neuroophthalmology. 2017 Dec. 41 (6):306-309. Online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764063/.).