INCIDENTAL PITUITARY LESION -Diagnostic approach

Albert Beckers&

JF BonnevilleService d’Endocrinologie

Centre Hospitalier Universitaire de Liège Université de Liège, Belgique

Rome - November, 2019Le fils de l'homme by René Magritte, 1964Private collection

Is There a Lesion ?

Ø Normal variant: « large » pituitary in small sella

Ø Physiologic hypertrophy: pregnancy, puberty

Ø Secondary enlargement:

• Lack of feedback : primary hypothyroidism, Klinefelter syndrome

• Hypersecretion of releasing hormones (CRH, GHRH)

Ø Technical artifacts

Possible pitfalls

Pitfalls in imaging-pituitary pseudoenlargement

Normal T1 and T2 signalsNormal enhancement after gadolinium injection

Ø small or flat sella, extensive pneumatizationof sphenoid sinus

Ø small sella and thick dorsum sellae

Ø extensive sphenoid sinus pneumatization and a narrow sella in an adolescent girl

?Isointensepituitary adenoma or ‘pituitary hyperplasia’

?Bulging of the normal-sized pituitary gland

YES

‘Kissing’ internal carotid arteries.

Narrow sellar content due to unusually large inferior coronary sinus, a sellar spine or a medial deviation of the internal carotid or trigeminal arteries

Trigeminal artery piercing the dorsum sella

Pitfalls in imaging-Vascular anomalies

Pituitary imaging - differential diagnosis

A large T1-isointense RCC with

an intracystic T2-hypointense nodule associated with

an enlarged inferior coronary sinusin a female with intracranial hypotension

after failed lumbar puncture.

Enlarged pituitary content of multiple origins

”Little Hut” - a Russian fairy tale of forest animals living in a house, which was too small for the bear

Pituitary imaging - secondary enlargement of pituitary

Primary hypothyroidism in a 9-yo girl. Regular enlargement of a homogeneous pituitary gland (upward convexity).

Pituitary imaging - technical artifacts

'Luminous 99' by Sergey Morshch, 2016, Contemporary art gallery, San Francisco

Ø Partial volume artifacts (parts of different anatomical structures)

Ø Magnetic susceptibility artifacts (at the interface betweenanatomical structures with different signal intensities)

Ø Flux artifacts (due to pulsating internal carotid arteries and cerebrospinal fluid)

Ø Chemical shift artifacts and ghosting (high signal of fat)

Posterior lobe mimicking a pituitary lesionon coronal T2-weighted image

Pituitary imaging - differential diagnosis

Deep fossula hypophyseos on axial CT

A posteriorly located pituitary adenoma ?

Etiology

Anterior pituitary tumoursØ Pituitary adenoma

Macro / microFunctioning / non-functioning

Ø Pituitary hyperplasiaØ Pituitary carcinoma

Posterior pituitary tumoursØ PituitocytomaØ Granular cell tumours

Malformative lesionsØ Rathke’s cleft cystØ DermoidØ EpidermoidØ Arachnoid cystØ Hamartoma

Benign parasellar tumoursØ MeningiomaØ CraniopharyngiomaØ NeurinomaØ Lipoma

Malignant tumoursØ GliomaØ Germ cell tumourØ Primary lymphomaØ ChordomaØ ChondrosarcomaØ ChondromaØ EpendymoblastomaØ PlasmocytomaØ Pituitary metastases

Inflammatory and granulomatous lesionsØ Lymphocytic hypophysitisØ Granulomatous hypophysitisØ Langerhans’ cell histiocytosisØ TuberculosisØ SarcoidosisØ Pituitary abscess

Vascular lesionsØ Aneurysms Ø Cavernous angiomasØ Cavernous sinus thrombosis

Vasilev V, Rostomyan L et al., EJE 2016

Etiology

Final clinical diagnosis of 282 incidentalomas

Histological diagnosis of operated cases and estimated diagnosis in non-surgical group

Famini P, Maya MM, Melmed S, JCEM 2011

Sanno N et al., EJE 2003

Nonfunctioning pituitary adenomas are the most frequent among etiologies

• Independently of the initial visualisation method

• Also confirmed histologically in surgical series

Pituitary imaging -Nature of incidental lesions

PITUITARY ADENOMA - Usually micro, non-functioning

Intrasellar microadenomas:• Lateralization inside the adenohypophysis• Possible deformation of the sellar diaphragm• Possible displacement of the pituitary stalk

Micro PRL: T1- hypointense and T2-hyperintenseMicro GH: T2 iso- or hypointense

!!! Unrecognized large non-functioning / gonadotroph PAs

!!! Unsuspected, subclinical or silent PRL, GH, ACTH secretion

Solid lesions

Pituitary imaging – pituitary adenoma

T1-hypointense and T2-hyperintense on coronal images.

Microprolactinoma

Attention!• drug-induced hyperprolactinemia ...• hypothalamic-pituitary stalk damage• false hyperprolactinemia ... macroprolactinemia

How to assess at endocrinology appointment

1. Complete history

2. Physical evaluation

3. Hormonal analysis

4. Visual field defects assessment5. * MRI scan (specific pituitary

protocol with fine cuts through the sella)if initial study was a CT or brain MRI

Is it causing any:

? Hormonal hypersecretion

? Hormonal hyposecretion

? Mass effects

Freda PU et al., JCEM 2011

Hyper

PRL – 10-40% of PA, stalk compression

GH – silent GH-secretion, medical comorbidities

ACTH – silent corticotropinoma, risk of progression to overt Cushing’s

Gonadotropins – rarely cause clinical symptoms

TSH – rare type of functioning PA

Alteration in pituitary function

Freda PU et al., JCEM 2011

Alteration in pituitary function

HypoChronic hypopituitarism results in general symptomatology (hypotension, generalized weekness, hypothermia, malaise, depression…)

Macroadenomas / larger microadenomas (6-9 mm) - screening recommended

Smaller microadenomas (<6mm) - screen only if clinically indicated

Clinical and laboratory evaluation for hypopituitarism:Hypogonadism (30%)Hypothyroidism (28%)Adrenal insufficiency (18%)GH insufficiency (8%)

Freda PU et al., JCEM 2011

Additional Work-up

HeadacheNeurological defects

Visual field defects ... in all macroadenomas and

microadenomas abutting or compressing

the optic nerves or chiasma on MRI,

even if there are no apparent visual symptoms(in 5-15% unrecognized visual field defects at

presentation)

Tumor mass effect

Freda PU et al., JCEM 2011

Vasilev V, Rostomyan L et al., EJE 2016

Pituitary imaging - differential diagnosis

Presellar meningioma inserted on the planum sphenoidale (arrow)It has stronger enhancement than the pituitary gland (marked with asterisk)

Solid lesions

MENINGIOMA• Sella is not enlarged • Normal pituitary tissue is

visualized• T1 - isointense and T2

hyperintense• “Dural tail” and homogeneous on

enhancement

Sagittal T1 Sagittal T2

Sagittal contrast-enhanced T1 Coronal contrast-enhanced T1

Pituitary imaging - differential diagnosis

Enlarged sellar content abutting the optic chiasm (curved arrow)The lesion is T1-isointense, T2-hyperintense, and becomes markedly enhanced after gadolinium injectionThe dural tail is shown with arrows

Solid lesionsCoronal T1 Coronal T2

Coronal contrast-enhanced T1 Sagittal contrast-enhanced T1

LYMPHOCYTIC HYPOPHYSITIS• Symmetric homogeneous

enlargement of the pituitary• Frequent suprasellar extension• Thickening of the stalk• Intense contrast accumulation

Pituitary imaging - differential diagnosis

Mucoid RCC located in the midline between the anterior and posterior lobes

Cystic lesions

axial T1 coronal T1

RCC on the upper surface of the pituitary, as an ‘egg in an egg cup’

RATHKE CLEFT CYST• Mostly intrasellar• Or lie on the sellar diaphragm

(‘egg in an egg cup’)• Frequently T1-hyperintense• T2-hypointense intracystic

nodules (cholesterol)• Usually no contrast

enhancement• Limited mass effects ( on sella

enlargement, posterior lobe, pituitary stalk…)

CASE 1 – Clinical presentation

A 55-yo man had a fall-related cervical spine injury treated conservatively with a neck brace during 10 weeks

Ø CT- scan was performed revealing a lesion in the sellarregion

Ø Patient had no particular complains and no symptoms related to this lesion at clinical evaluation at referral

CASE 1 – Further evaluation

Visual fields evaluation: Superotemporal loss on right side

Laboratory tests: No hormonal hyper- or hyposecretion

TRANSSPHENOIDAL SURGERY

Pathology findings: Non-secreting pituitary adenoma, Ki67 1-2%

Pituitary MRI :

Pituitary macroadenoma

20x13x19 mm

with suprasellar extension and contact with the right optic nerve

CASE 2 – Clinical presentation

A 79-yo man referred to the emergency room with a head trauma and a large face wound

Ø On CT- scan a large sellar lesion with suprasellar extension was revealed (18x21x28mm)

Ø No signs / symptoms related to this lesion at clinical evaluation

CASE 2 – Further evaluation

Ophtalmological evaluation: Bitemporal superior quadrantanopiaLaboratory tests: FSH 22 U/l

gonadotrophinoma?age-related primary hypogonadism?

Pituitary MRI : Pituitary macroadenoma (max Ø 28 mm) with suprasellar extension compressing the optic chiasma and invasion in the left cavernous sinus

→

0.5 mg x 2 per weekCABERGOLINE

Ø amelioration in visual field defect

Ø shrinkage of pituitary tumor size (25 mm)

CASE 3 – Clinical presentation

A 80-yo man underwent a brain CT-scan for an episode of confusion after aortic valve replacement and coronary arterybypass surgery

Ø On CT- scan a large sellar lesion with suprasellar extension and invasion in sphenoidal sinuses was revealed

Ø No signs / symptoms related to this lesion at clinical evaluation

CASE 3 – Further evaluation

Ophtalmological evaluation: Bitemporal hemianopiaLaboratory tests: IGF-1 : 539 µg/l

GH : 24.56 µg/lPRL : 17.6 µg/l+ hypogonadotropic hypogonadism+ central hypothyroidism

Pituitary MRI : Pituitary giant macroadenoma (max Ø 55 mm) with intrasellar and suprasellar extension and invasion in the surrounding structures

CASE 3 – Further evaluation

Rhinorrhea

→0.5 mg x 3 per week

CABERGOLINE

Ø shrinkage of pituitary tumor size

IGF-1 439 µg/l, GH 1.87 µg/l, PRL 0.1 µg/l

100 µg x 3 per daySANDOSTATIN +

Stop treatmentØ expansion of pituitary tumor with

increase in chiasma compressionIGF-1 529 µg/l, GH 8.55 µg/l, PRL 1 µg/l

Restart treatmentØ shrinkage of pituitary tumor size,

amelioration in visual field lossIGF-1 361 µg/l, GH 2.36 µg/l

Take home message

Ø 90% - Pituitary adenomas + Rathke Cleft Cyst 10% → could be anything, sometimes a challenge

Ø It is important to correlate the images with history & all clinical data

• Detailed history and physical evaluation (hormonal hyper- or hyposecretion, tumor mass effects)

• Screen for hormone hyperfunction – check prolactin in all pituitary incidentalomas, consider screening for Cushing’s and acromegaly at time of identification and other hormones if clinically suspicious

• Screen for hormone hypofunction – in macroadenomas• Refer for visual field assessment if close to the optic chiasm