Magnetic Resonance

Imaging of Pituitary TumorsDr Khalili

Endocrinologist

Magnetic Resonance Imaging (MRI) is currently considered a major

keystone of the diagnosis of diseases of the hypothalamic-hypophyseal

region.

However,

the relatively small size of the pituitary gland,

its location deep at the skull base and

the numerous physiological variants present in this area

impede the precise assessment of the

anatomical structures and, particularly, of the pituitary gland itself

The diagnosis of the often tiny lesions of this region – such as pituitary

microadenomas – is then difficult if the MRI technology is not optimized

and if potential artifacts and traps are not recognized.

Advanced MRI technology can not only depict small lesions with greater

reliability, but also help in the differential diagnosis of large tumors.

Pituitary adenomas represent the most common pathology

of the sellar region.

They become symptomatic if they exert a

mass effect on the surrounding structures, or

in cases of hormonal hypersecretion.

Pituitary adenomas are frequently discovered by chance.

MRI has totally supplanted CT (computed tomography)

in the diagnosis of these lesions.

CT is still obtained in rare cases, including the search for

tumor calcifications when a craniopharyngioma is suspected, or of

bone erosion in the presurgical assessment of the clivus in aggressive

pituitary adenomas.

The Normal Pituitary Gland

The pituitary gland is routinely examined in sagittal and

coronal projections in every case, and in axial projections in

some particular circumstances.

In our practice, gadolinium injection is not always mandatory and depends

on the results of nonenhanced sequences.

Fig. 1. Sagittal T1-weighted image obtained to

determine coronal projections.

Coronal sequences are obtained perpendicularly

to the subcallosal plane.

Coronal T1- and T2-weighted sequences are always performed perpendicularly to a reference

plan drawn on the sagittal view, e.g. a line tangential to the inferior surface of the corpus callosum

( fig. 1 ).

This strategy permits a perfect comparison of images

on serial MRIs.

In normal subjects, the shape of the anterior pituitary is variable on coronal images, with a

flat,concave or convex upper surface;

its height can vary considerably from 1–2 to 7–8 mm.

The T1-weighted signal of the normal anterior pituitary gland is strictly

identical to that of the cerebral white matter,

The posterior lobe can be masked by the dorsum sellae in the T1-weighted

sagittal view,

so that its demonstration is best obtained on

axial T1- weighted fat-saturated sequences.

After intravenous gadolinium injection, enhancement of the anterior

pituitary, pituitary stalk and tuber cinereum is normally observed ( fig. 2 ).

Fig. 2. MRI of the normal pituitary gland. a , b Coronal

T1- and T2-weighted images.

c Axial T1-weighted fat-saturated image (the arrow

points to the posterior lobe).

d Sagittal T1-weighted image: anterior pituitary (1); posterior pituitary (2);

pituitary stalk (3); 3rd ventricle (4).

e Contrastenhanced sagittal T1-weighted MRI: enhancement of the

anterior pituitary, the pituitary stalk and the tuber cinereum (arrow). f

Anatomic representation of the normal sellar region;

Pituitary Adenomas

The MRI aspect of pituitary adenomas is described

according to their size and their hormonal secretion.

Pituitary Microadenomas

Pituitary microadenomas are defined as tumors measuring

less than 10 mm in diameter.

the term ‘picoadenomas’ is proposed for adenomas measuring less than 3 mm that frequently need specific technical options, such as the search for

corticotropic adenomas.

Pituitary microadenomas have to be

differentiated from:

– artifacts,

– normal anatomical structures, such as the posterior

Pituitary

– variants from normal, such as unusual intrasellar

arteries,

– intrasellar cysts, such as Rathke’s cleft cysts (RCC),

a small sella turcica can also mimic a pituitary gland enlargement;

frequently associated with an extensive sphenoidal sinus pneumatization,

( fig. 3 ).

Fig. 3. a , b Small sella, short sellar floor and

hyperpneumatization of the sphenoid bone

(frontal view).

Dynamic imaging has to be read with caution and can be

the source of false positive diagnoses: ( fig. 4 ).

Fig. 4. a–e Hazard of dynamic MRI:

normal delayed enhancement of the

anterior pituitary gland wrongly interpreted

as a microadenoma (arrow

in c ). The off-midline posterior lobe

enhances earlier because of its direct

blood supply.

b

a

c

c

Microprolactinomas

Microprolactinomas are the most frequent pituitary microadenomas.

They are usually round or oval in shape,

located off midline,

hypointense on T1-weighted images, as compared to the normal anterior

pituitary gland, and

more or less hyperintense on T2-weighted images.

Microprolactinomas generally have a T1-weighted signal similar to the

cerebral gray matter,

while the normal unaffected anterior

pituitary gland has the same T1-weighted signal as the cerebral

white matter ( fig. 5 ).

Fig. 5. Typical microprolactinoma MRI pattern:

the adenoma is located in the top right side of the pituitary and appears

hypointense on T1-weighted images and

Hyperintense on T2-weighted images ( a );

Unusual hypointensemicroprolactinoma on a

T2-weighted image, before and after gadolinium injection ( b ).

a b

High signal intensity on T1-weighted images can sometimes be observed,

reflecting hemorrhagic transformation, not uncommon even in

asymptomatic patients with prolactinomas .

Intratumoral calcifications are very rare, but do not rule out the diagnosis

of pituitary adenomas, particularly in men.

An additional CT scan can be helpful in these cases.

some relationship between the tumor T2 signal and the serum prolactin

levels;

the more hyperintense the tumor, the lower the prolactin

levels are.

T2 hypointense microprolactinomas are very unusual;

they seem to be associated with higher prolactin levels

and can possibly have a different evolution, e.g. arise during

pregnancy ( fig. 6 , 7 ).

Fig. 6. Normal appearance of the pituitary in the 7th month of a

normal pregnancy: the gland is enlarged and hyperintense on T1-weighted MRI images ( a ); microprolactinoma before cabergoline

treatment ( b ), and moderate adenoma enlargement in the 7th

month of pregnancy after cabergoline withdrawal ( c ).

Fig. 7. A 27-year-old female with ‘post-pill’ amenorrhea; prolactin was 4,000 mIU/l. Left-sided prolactinoma with an unusual T2-hypointense signal ( a ); T1- ( b ) and post-contrast T1-weighted sequences ( c ).Pregnancy occurred quickly after dopamine agonist treatment and was stopped as soon as the pregnancy was determined ( d ). On the coronal T2-weighted image, a clear enlargement of the adenoma in the 8th month of pregnancy is seen, with tilting of the optic chiasm. Cabergoline was

reintroduced and normal delivery occurred. At follow-up,4 months after delivery, there was shrinkage of the mass and a slight hemorrhagic transformation of the adenoma ( e ). f Further reduction ofthe lesion 1 year after delivery.

There is generally a good correlation between the prolactin

level and adenoma size, except for extremely T2-hyperintense

and T1-hyperintense lesions as these situations usually

correspond to tumors secreting low amounts of prolactin .

We have almost never detected a microprolactinoma

with a prolactin level <1,000 mIU/l (35 μg/l) on MRI.

Indirect radiological signs of a microadenoma are changes

of the sellar floor and an upper convex surface.

The pituitary stalk displacement is not always helpful for diagnosis.

However, a localized subtle deformation of the sellar floor is a valuable

indicator, even for small microadenomas .

When the radiological diagnosis is obvious after T2- and

T1-weighted sequences in a context of infertility, amenorrhea-

galactorrhea and hyperprolactinemia, we consider

contrast-enhanced sequences unnecessary.

On the contrary,contrast medium injection must be used in all uncertain

situations, e.g. if an isointense or hypointense pituitary microadenoma is

suspected.

Shrinkage of microprolactinomas is normally observed

after a few weeks of treatment with dopamine agonists.

Most of the time, an accentuation of high T2-intensity is also seen.

A partial hemorrhagic transformation of the adenoma can mask its

shrinkage.

Enlargement in size, usually a doubling, of the microadenoma occurs

during pregnancy, principally during the third trimester, if dopamine

agonists have been withdrawn

In the same way, the volume of the normal anterior pituitary gland

increases – on average by 0.08 mm per week – and its T1-weighted signal

increases.

Return to the prepregnancy size of the adenoma and of normal pituitary

gland shape is usually observed a few weeks after delivery

In some particular conditions, such as

hemorrhagic transformation of the adenoma,

a second pregnancy or

prolonged medical treatment during pregnancy,

a reduction of size or even the disappearance of the adenoma at MRI can

sometimes be observed, paralleled by the normalization of prolactin levels.

Growth Hormone-Secreting

Microadenomas

Growth hormone (GH)-secreting microadenomas were

previously underdiagnosed, while to date they represent

one third of all somatotropinomas.

Indeed, with high-resolution MRI, particularly in elderly subjects, it has

become possible to reveal tiny pituitary adenomas – sometimes within an

enlarged sella, erroneously called ‘empty sella’– corresponding to

involuted adenomas, either spontaneously or after hemorrhage .

Fig. 8. T2-weighted images of a well-defined,

hypointense GH-secreting

microadenoma.

More than half of microsomatotropinas as well

as GH-secreting pituitary macroadenomas

present with hypointensity on T2-weighted

images, if compared with the unaffected

pituitary gland

Fig. 9. Corticotroph ‘picoadenoma’ demonstrated

with optimized MRI techniques

Corticotroph microadenomas represent a difficult

challenge

for the neuroradiologist, their size being sometimes

at the limit or below the radiological visibility

Corticotroph Microadenomas

In cases of negative MRI examination, it is recommended to

resume MRI and to add alternative sequences, such as delayed

imaging studies, dynamic MRI, 3D imaging and other

variants

Recently, Erickson et al. have confirmed that 3-tesla MRI is significantly

more sensitive than 1.5-tesla MRI and should become

the gold standard for the evaluation of patients with

ACTH-dependent Cushing’s disease.

Ikeda et al. found a high accuracy of microadenoma

localization at surgery using composite images

from methionine positron emission tomography (METPET)

and 3-tesla MRI, but this has not been introduced into

clinical practice.

Pituitary Macroadenomas

Pituitary Nonfunctioning

Macroadenomas

Pituitary nonfunctioning macroadenomas are predominantly

localized within an enlarged sella turcica.

They often also present with extrasellar extension, upwards into the

suprasellar cistern, downwards into the sphenoid sinus or laterally into the

cavernous sinus.

The normal residual pituitary tissue is compressed and pushed laterally,

towards one side, and superiorly, but never inferiorly.

Upwards extension is present in more than 70% of patients

with possible contact, or even compression, of the

optic chiasm.

The sellar diaphragm can function like a ‘belt’,

thus giving the adenoma an hourglass shape ( fig. 10 ).

Fig. 10. So-called ‘snowman’ hemorrhagic

pituitary macroadenoma with hyperintensity

of the upper part of the tumor on the T1-

weighted image and hypointensity on the

T2-weighted image. a, b Postgadolinium

coronal T1- and T2-weighted images. c, d

Postgadolinium sagittal T1- and T2-weighted

images.

The suprasellar component of large

macroadenomas is often

multilobular.

Fig. 11. Pituitary macroadenoma with

suprasellar extension.

T2 hyperintensity within the optic chiasm

could indicate a nonrecovery of the visual

field defect despite surgery.

Hyperintensity of the optic chiasm on T2-weighted

images can indicate a poor prognosis for the visual

function even after quick removal of the pituitary

adenoma responsible for optic pathway

compression

Downwards extension of pituitary nonfunctioning

adenomas is more rare than in GH-secreting tumors.

Fig. 12. Pituitary macroadenoma invading the sphenoid sinus and eroding the clivus. a, b

Sagittal T1- and T2-weighted images. c Sagittal

reformatted CT.

MRI, or even better CT, demonstrates a focal or widespread defect of the

more anterior, upper portion of the clivus

The signal intensity of nonfunctioning macroadenomas

is usually inhomogeneous, particularly on the T2-weighted

images, with disseminated areas of hyperintensities which

reflect cystic or necrotic components.

The posterior lobe is hyperintense in T1-weighted sequences. It is

compressed, flattened and best identified in the axial noncontrast

projection.

Aberrant storage of antidiuretic hormone in the socalled

‘ectopic posterior lobe’ occurs when the pituitary stalk

is severely compressed, i.e. in practice with pituitary adenomas

>20 mm in height.

An ectopic posterior lobe may be present with smaller adenomas after

hemorrhagic events or after surgery.

Enlargement of an ectopic posterior lobe can occur with time, sometimes

described as a ‘nodule’ in the opticochiasmatic cistern, particularly on CT examination.

Fig. 13. Pituitary macroadenomas: lateral displacement of the normal pituitary tissue

( a ) and the dural tail (not specific; b ).

Gadolinium injection enhances the normal pituitary tissue,

which is located superiorly and/or laterally on one side,

but never inferiorly

Postgadolinium enhancement of the dura, the socalled

‘dural tail’, is not specific of meningiomas and has been described with large

pituitary adenomas, particularly if

they are hemorrhagic or

soon after surgery, as well as with

perisellar aneurysms

Intratumoral Hemorrhage

Intratumoral hemorrhage typically occurs in pituitary adenomas

and much less frequently in other types of pituitary tumors.

Hemorrhage classically appears with high signal intensity on T1-weighted

images, and either as an intratumoral dark mass or as a cyst with a dark rim

on T2-weighted images, which indicates a hematoma or hemorrhagic cyst.

Tosaka et al. consider T2-weighted gradient-echo MRI the most sensitive

technique for the detection of blood, in particular in hyperacute and

chronic hemorrhages.

Fig. 14. Pituitary macroadenomas: the fluidfluid

level indicates an old hemorrhage.

a

Pituitary Apoplexy

The diagnosis of pituitary apoplexy is made clinically. It is usually caused by

infarction or hemorrhage of a previously undiagnosed pituitary

macroadenoma, typically a nonfunctioning adenoma.

This clinical syndrome, characterized by sudden headache, oculomotor

nerve palsy and asthenia, can mimic subarachnoid hemorrhage, stroke or

meningitis.

A radiological diagnosis may be difficult in the early stage.

The classical predominant hyperintensity on T1-weighted images

is frequently absent because infarction or hemorrhage are still in the form of

deoxyhemoglobin.

However, sequential MRI will demonstrate the progressive increase of

T1-weighted hyperintensity, with the passage from deoxyhemoglobin

to methemoglobin.

T2-weighted gradient-echo MRI can be helpful in this case, making

pituitary hemorrhage appear as a ‘dark mass’

Fig. 15. Pituitary apoplexy with a sudden onset

of headache 24 h before. a Coronal T1-

weighted image: ‘striated’ pattern of a pituitary

mass without evidence of hemorrhage.

b Diffusion-weighted MRI: increased signal

intensity (arrow) within the pituitary mass.

c ADC map showing decreased signal intensity.

d Coronal T1-weighted image 2 days later:

peripheral T1-hyperintensity represents

methemoglobin.

a

b c

Finally, reactive thickening of the sphenoid sinus mucosa constitutes a

reliable sign, present from the early stage

If surgery is postponed or not indicated, shrinkage of the mass usually

occurs within several weeks

Prolactinomas in Men

Prolactinomas in men are most often large or very large and

frequently invasive.

Extension into the sphenoid sinus can be impressive and mimic a primitive sphenoid sinus tumor.

Prolactin levels are usually much higher than in females and

can reach hundreds of thousands mIU/l.

Tumor shrinkage and T2-weighted hyperintensity occur very rapidly

with dopamine agonist treatment ( fig. 16 ).

Shrinkage of large invasive macroprolactinomas can exceptionally lead to

cerebrospinal fluid fistula

Fig. 16. a Macroprolactinoma with suprasellar extension. b Six weeks after dopamine agonist

treatment. c After the patient stopped treatment.d–f Shrinkage of the adenoma after reinstitution of

medical treatment on sequential MRIs, 2 months, 1 and 2 years later, respectively

a

GH-Secreting Macroadenomas

GH-secreting pituitary macroadenomas present specific

characteristics.

According to personal data obtained from MRI performed in 300

acromegalic patients, two thirds of them were macroadenomas and 71%

extended predominantly downwards into the sphenoid sinus ( fig. 17 a).

Fig. 17. GH-secreting macroadenomas: predominant

inferior extension ( a ) and isolated

inferior extension ( b ).

Chiasmatic compression and resulting visual field defects were

present in only 17% of the cases .

This explains in part the long delay frequently observed between the onset

of symptoms and the diagnosis.

An isolated inferior extension, i.e. without any extension above the sellar

diaphragm level ( fig. 17 b), was found by Zada et al. in 24% of

somatotropinomas;

The T2-weighted MRI signal appears hypointense in 52% of GH-secreting

pituitary adenomas, as compared to the normal pituitary gland.

Most of these T2-hypointense adenomas present a well-defined round or

oval contour ( fig. 18 )

Fig. 18. Two different types of GH-secreting

pituitary adenomas: T2-hypointense ( a ) and

T2-hyperintense ( b ) to the normal pituitary

gland.

Fig. 22. GH-secreting pituitary

adenomas

before ( a , b ) and after somatostatin

analogs

( a’ , b’ ). Only the T2-hypointense

adenoma

( b, b’ ) shrank.

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