Review Pituitary Apoplexy...Pathophysiology of Pituitary Apoplexy 5 Hemorrhage 1.Suri, H.,...

1

Date:2020.2.27

Speaker:R1 An Che, Cheng

Supervisor: VS Chih Jen, Cheng

Review

Pituitary Apoplexy

Introduction

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Pituitary apoplexy is a clinical syndrome, characterized by

sudden onset of headache, visual impairment and

decreased consciousness caused by abrupt hemorrhage

and/or infarction of the pituitary gland, generally within a

pituitary adenoma

Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20. .

Hormone Secretion of Pituitary Gland

3 Modified from The Netter Collection of Medical Illustrations: Endocrine System Vol.2

TSH

ACTH

LH

FSH

Prolactin

GH

Oxytocin

ADH

Posterior pituitary gland Anterior pituitary gland

Hypothalamus

Anatomy of Pituitary Gland

4 Modified from Netter, Netter’s Atlas of Human Anatomy

III cranial nerve

Optic chiasm Pituitary gland

IV cranial nerve

V1 cranial nerve

V2 cranial nerve

VI cranial nerve

Internal carotid artery

Sphenoidal sinus

Pathophysiology of Pituitary Apoplexy

5

Hemorrhage

1.Suri, H., Dougherty, C. Presentation and Management of Headache in Pituitary Apoplexy. Curr Pain Headache Rep 23, 61 (2019)

2.Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45..

Precipitating

factors

Reduced

perfusion

Increased

intrasellar pressure

Infarction

Vasculopathy

Tumor outgrowth of

blood supply


Sudden increased


Increased pressure on

adjacent vascular and

neural structure

Neural palsy

(CN.III, IV, V, VI)




Sudden increased




neural structure

Pressure transmitted on

brain stem/hypothalamus Consciousness

impairment

Neural palsy

(CN.III, IV, V, VI)




Sudden increased




neural structure


brain stem/hypothalamus

Optic chiasm

compression

Visual

Defect

Consciousness

impairment

Neural palsy

(CN.III, IV, V, VI)




Sudden increased


Compression of

normal pituitary gland



neural structure

Hypopituitarism


brain stem/hypothalamus

Optic chiasm

compression

Visual

Defect

Consciousness

impairment

Neural palsy

(CN.III, IV, V, VI)



Epidemiology

10

1.Raappana A, Koivukangas J, Ebeling T, Pirilä T. Incidence of pituitary adenomas in Northern Finland in 1992–2007. J Clin Endocrinol Metab.

2010;95:4268–4275

2.FernandezAKaravitakiNWassJA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK).

Clinical Endocrinology 201072377–382.

More than 80% have an underlying pituitary adenoma, but it

can occur in non-adenomatous lesions, such as sellar

tuberculoma, and sellar metastasis, or normal pituitary gland

Prevalence is about 6.2 cases/100 000 population

Incidence is about 0.17 episodes/100,000 person-years

Most frequent in the fifth or sixth decade

Male : Female is about 2:1

Precipitating Factors

11

Systemic hypertension (26%) Dopamine agonists

Anticoagulation therapy (25%) Radiation therapy

Major surgery, in particular Cardiac

surgery(18%)

Dengue haemorrhagic fever

Pituitary function tests with GnRH,

TRH and CRH

Coagulopathies

Pregnancy and Delivery Cerebral angiopathy

Estrogen therapy

Head trauma

Precipitating factors have been found in 40% of cases The majority of cases occur spontaneously

1.Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20

2.Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45... .

Clinical Presentation

Clinical manifestation Frequency

Headache >90%

Nausea and vomiting 43~80%

Visual impairment

Visual fields defects or decreased visual acuity 36~71%

Diplopia >50%

Altered mental state 13–42%

Hypopituitarism

ACTH deficiency 70~76%

Gonadotrophin deficiency 76~79%

Central hypothyroidism 50~57%

Panhypopituitarism 70%

Hyponatremia 12~44%

Cristina Capatina ,Warrick Inder ,Niki Karavitaki et.al1 MANAGEMENT OF ENDOCRINE DISEASE: Pituitary tumour apoplexyin

European Journal of Endocrinology May 2015 Volume 172: Issue 5, European Society of Endocrinology

Clinical Presentation

Himanshu Suri & Carrie Dougherty. Presentation and Management of Headache in Pituitary Apoplexy; Current Pain and Headache Reports

volume 23, Article number: 61 .2019.

.

Presentations of Headache in Pituitary Apoplexy

Nearly half (45.8%) in a retrospective series of 60 patients

presented with severe acute thunderclap headache with

maximum intensity at onset.

Some presented with a gradual onset, unremitting

headache of several weeks duration.

Few cases throbbing and associated with nausea,

phonophobia, and mild photophobia, mimicking migraine

Diagnostic Evaluation

14

Patients presenting with acute severe headache with or without

neuro‐ophthalmic signs

Patients known to have a pituitary tumor

Patients known to have a pituitary tumor when performing pituitary

stimulation tests, anticoagulation therapy or undertaking coronary

artery bypass or other major surgery

Who Should be Suspected

Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20.


15

Role of Computerized Tomography(CT)

Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45...

To rule out SAH in patients with severe, sudden onset

headace

It shows an intrasellar mass in 80% of cases, but was

diagnostic in only 21–28% of cases

In non-hemorrhage apoplexy, CT may be non- specific

CT provides better hemorrhage detection in hyperacute

stage(few hours from onset) than MRI.


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Image Findings Non-contrast CT in Hemorrhage of Pituitary Apoplexy

Pradeep Goyal1, Michael Utz2, Nishant Gupta. Et.al Clinical and imaging features of pituitary apoplexy and role of imaging in differentiation of

clinical mimics Vol 8, No 2 March 2018

Hyperdense lesion in acute hemorrhage(few hours from onset)


17

Role of Magnetic Resonance Imaging(MRI)

1.Cristina Capatina, Warrick Inder , Niki Karavitaki et.al. MANAGEMENT OF ENDOCRINE DISEASE: Pituitary tumour apoplexy Volume 172:

Issue 5 May 2015

2.Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20.

Confirm the diagnosis of pituitary apoplexy in over 90% of the patients

MRI can identify hemorrhagic and necrotic areas and show the relationship

between the tumor and neighboring structures

In the first few hours, hemorrhage can be missed on MRI and is better

identified with CT

https://eje.bioscientifica.com/view/journals/eje/172/5/R179.xml#affiliation0

https://eje.bioscientifica.com/view/journals/eje/172/5/eje.172.issue-5.xml


18

Image Findings

Normal Pituitary Gland in MRI

Dr Mostafa El-Feky and Assoc Prof Frank Gaillard et al. Pituitary MRI . Radiopaedia. 23rd Apr 2012.

Iso-intense

Sagittal T1

Pre-contrast


19

Image findings



Contrast enhanced

Hyper-intense

Sagittal T1

Post-contrast


20

Image findings



Coronal T2

Hyper-intense


21

Image Findings

CT and MRI in Hemorrhage Apoplexy

Modified from Dr Mostafa El-Feky and Assoc Prof Frank Gaillard et al. Timeline diagram of MRI and CT characteristics of intracerebral hemorrhage

.Radiopaedia.. 19th Sep 2017

Hyperacute

<12 hours

Acute

12-48 hours

Subacute

>2 days

Chronic

>14 days

Isodense

Isointense

Isointense


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Image Findings MRI of Hemorrhage Apoplexy in Acute Stage(12~48hours)



Hyper-intense

Sagittal T1

Pre-contrast

Hypo-intense

Sagittal T1

post-contrast

Hypo-intense

Coronal T2


23

Image Findings

MRI in Non-hemorrhage Apoplexy

In acute phase, both hemorrhagic and non-hemorrhagic

apoplexy show high signal on diffusion weighted

imaging(DWI)

After intravenous contrast, the most common finding in

both hemorrhagic and non-hemorrhagic apoplexy is

peripheral rim enhancement in acute phase




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Image Findings MRI in Non-hemorrhage Apoplexy in Hyepracute stage



High signal

DWI

Rim enhancement

SagittalT1

post-contrast

Iso-intense

SagittalT1

pre-contrast


25 Modified from Dr Mostafa El-Feky and Assoc Prof Frank Gaillard et al. Timeline diagram of MRI and CT characteristics of intracerebral hemorrhage

.Radiopaedia.. 19th Sep 2017

Hyperacute

<12 hours

Acute

12-48 hours

Subacute

>2 days

Chronic

>14 days

Isodense

Isointense

Isointense

Back to Our Case


26

Axial T1

Pre-contrast

Heterogonous

Hyper-intense

Back to Our Case


27

Axial T1

Post-contrast

Hypo-intense

Back to Our Case


28

Axial T2

Heterogonous

Hyper-intense

Back to Our Case


29

Differential Diagnosis

Pregnancy Hyperplasia

During pregnancy there is progressive enlargement of the pituitary gland. Patient may

present with headache with visual field deficits and can have acute hypopituitarism.

Sagittal T1

pre-contrast

Large pituitary gland

Axial T1

pre-contrast

No focal

Hyper-intense


30

Differential Diagnosis

Rathke's Cleft Cyst(RCC)

Epithelial cysts arising from remnants of the Rathke pouch in the pituitary

gland. A large sellar RCC may mimic pituitary apoplexy clinically

Coronal T2

Heterogeneously

Hypo-intense

Coronal CT

Sellar mass with

fluid debris

level

Management

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Supportive measures to ensure hemodynamic stability

Empiric corticosteroids replacement

Conservative treatment

Surgical intervention

Best approach is controversial

Therapeutic strategies

Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20.

Management

32

Empiric Corticosteroids Replacement

Corticotropic deficiency is the most life-threatening complication,

potentially causing severe hemodynamic problems

Indication:

Haemodynamic instability, impaired consciousness and

visual function

Treatment:

Hydrocortisone bolus 100–200 mg followed by 50–100 mg

every 6 hours

Tapered to maintenance dose of 20–30 mg/day, orally

1.Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20. 2.Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3:216–226.

Management

33

Conservative Treatment

Some retrospective studies have revealed that in patient with stable

visual deficits or improving, a conservative approach is safe, does not

result in poor visual or endocrine outcome

Indications

Patients without any neuro‐ophthalmic signs or improving

Operative high risk

Treatment

Glucocorticoids, replacement of hormone deficits

Monitoring of visual function, keep fluids and electrolytes balance.

1.Ayuk, J., McGregor, E.J., Mitchell, R.D. et al. (2004) Acute management of pituitary apoplexy–surgery or conservative management?.

2. Gruber, A., Clayton, J., Kumar, S. et al. (2006) Pituitary apoplexy: retrospective review of 30 patients–is surgical intervention always necessary? British

Journal of Neurosurgery, 20, 379–385

3.Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20. 4.Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45...

Management

34

Surgical Intervention

Indications

Visual fields and acuity impairment

Impaired consciousness

Deteriorating neurological signs

Conservative treatment failure

Timing

Preferably within the first 7 days of onset of symptoms

Complications

CSF leakage

Damage of normal pituitary

1.Peter M., De Tribolet N. Visual outcome after transsphenoidal surgery for pituitary adenomas. British Journal of Neurosurgery. 1995;9(2):151–158

2.Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary apoplexy. Clin Endocrinol (Oxf). 2011;74:9–20. 3.Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45...

Management

Best approach is still controversial

1.Sibal L, Ball SG, Connolly V. et.al. Pituitary apoplexy: a review of clinical presentation, management and outcome in 45 cases. Pituitary20047157–163..

2.BujawansaS, Thondam SK, Steele C et.al. Presentation, management and outcomes in acute pituitary apoplexy: a large single-centre experience from

the United Kingdom. Clinical Endocrinology 201480419–424.

3.Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45...

Available literature indicates that cases without severe, progressing

neuroophthalmic signs can safely be managed conservatively

There were selection bias to their retrospective design; the patients

in the conservative group had less severe condition than those in the

surgical group. Bearing this in mind, the endocrine and visual

outcomes are similar in operated and conservatively managed cases.

A randomized trial is needed for obtaining strong evidence.

Management

Adriana Albani, Francesco Ferraù, ,Filippo Flavio Angileri et.al Multidisciplinary Management of Pituitary Apoplexy Int J Endocrinol. 2016 Dec 15.

Suspected pituitary apoplexy

Multidisciplinary care (endocrinologist, neurosurgeon, ophthalmologist)

1. Keep hemodynamic stability, fluid electrolyte balance

2. Consider empiric steroid

3. Assessment of pituitary function

Urgent MRI(or CT if unavailable)

Assess for

Impairment of consciousness

Deterioration or visual disturbance

Surgery Conservative treatment

closely monitoring

No improvement

Outcome

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Motality:5–15.3%

Visual disturbance

Complete or significant improvement in visual disturbance

occurs in 57–86%

Endocrine

Hypogonadism remains in 55–79%, hypothyroidism in 45–60%,

and ACTH deficiency in 60–87%

Briet C1, Salenave S1, Bonneville JF1,et. Al. Pituitary Apoplexy Endocr Rev. 2015 Dec;36(6):622-45..

Take Home Messages

42

Pituitary tumor apoplexy is a rare, potentially life-

threatening clinical syndrome caused by ischemic

infarction or hemorrhage, generally into a pituitary tumor

The diagnosis should be suspected in all cases with

sudden-onset severe headache, with or without

neuroophthalmic manifestations

Take Home Messages

43

CT imaging is the most common initial study during the

acute onset symptoms

MRI having better sensitivity should always be performed

in acute and subacute phase

Take Home Messages

44

Patient should be under the care of a multidisciplinary

team including endocrinologist, neurosurgeon, and

ophthalmologist

In cases with severe, progressing visual or neurological

manifestations, surgical decompression is indicated;

Patients with mild, stable clinical picture can be managed

conservatively

Take Home Messages

45

The visual and neurological outcomes are favorable in

most cases.

The endocrinological prognosis is less favorable with

many patients requiring replacement therapy and long-

term follow-up.

The optimal treatment is debate. Prospective randomized

trials are necessary

Thank you for listening

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Review Pituitary Apoplexy...Pathophysiology of Pituitary Apoplexy 5 Hemorrhage 1.Suri, H.,...

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