1. GIANT PITUITARY
ADENOMAS
Sumit Sinha
M.S.; D.N.B.; M.Ch
Assistant Professor
Deptartment of Neurosurgery
All India Institute of Medical Sciences
New Delhi

2. GIANT PITUITARY ADENOMAS
➢ Pituitary adenomas – 7-17% of all the intracranial tumors
➢ 3rd commonest tumors after Gliomas and Meningiomas
➢ Mostly benign- limited to the sella
➢ Produce symptoms due to hormone production, local mass effect or both

3. GIANT PITUITARY ADENOMAS
➢ About 15% of them grow considerably to significant size- spread to the
extrasellar compartment- GIANT PITUITARY ADENOMAS
➢ Formidable surgical problem
➢ Identified as a separate category- aggressive behavior, higher prevalence of
neuro-ophthalmologic deficits and poorer response to surgery and
radiotherapy
➢ Raise distinct and complex management issues

4. GIANT PITUITARY ADENOMAS
Definition- AMBIGOUS
No distinct histopatholgical features
Rigid criterion are lacking
Symon and Jakuwoski (1979) *– MOST ACCEPTED DEFINITION:
➢ >40 mm above the planum sphnoidale in any direction
➢ < 6 mm from the highest point of the tumor to the FM
➢ Multidirectional spread in >2 directions
*Symon L, Jakuwoski J. Surgical treatment of giant pituitary adenomas. J
Neurol Neurosurg Psychiatry 1979; 42: 973-82

5. GIANT PITUITARY ADENOMAS
➢ Guiot et al – SS extension of >30 mm above the tuberculum sellae
➢ Mohr et al (1990) – SS extension >20 mm above the jugum sphenoidale in
any direction regardless of the intrasellar volume
➢ Garibi et al (2002) – Tumors >30 mm in diameter (Hardy Type D)
➢ Yildiz et al (1999) – Tumors > 40 mm in size
Other Definitions:

6. GIANT PITUITARY ADENOMAS
Grade 0- Intrapituitary adenoma, <1 cm, normal sella
Grade 1- Intrapituitary adenoma, <1 cm, focal bulging sella
Grade 2- Intrasellar adenoma, >1 cm, enlarged sella, no erosion
Grade 3- Diffuse adenoma, >1 cm, enlarged sella, localized erosion/
destruction
Grade 4- Invasive adenoma, >1 cm, ghost sella
Tumors with SS extension:
A: extending to SS cistern
B: extending to the IIIrd ventricle recess
C: extending to involve whole of the anterior IIIrd ventricles
Pituitary adenomas- Classification

7. GIANT PITUITARY ADENOMAS
Hardy and Vezina (1976)- (on the basis of PEG):
➢ Type A- SS extension bulges into chiasmatic cisterns
➢ Type B- Tumor reaches the floor of the IIIrd ventricle
➢ Type C- Tumor bulges into the IIIrd ventricle
➢ Type D- frontal or temporal fossa extensions
GPA- CLASSIFICATION:

8. GIANT PITUITARY ADENOMAS
Hashimoto et al (1981) – included
➢ Grade C- SS extension with gross III ventricle displacement
➢ Grade D- intracranial, intradural and parasellar extension
➢ Grade E- extradural extension into and beneath the CS
GPA- CLASSIFICATION:

9. GIANT PITUITARY ADENOMAS
Goel et al (2004) –
➢ Grade I- confined to the elevated diaphgrama/ bordered laterally by the
intact medial wall of the CS
➢ Grade II- Transgression and invasion into the medial wall of the CS
➢ Grade III- Elevation of the supr wall of the CS, with multicompartmental
extension
➢ Grade IV- Supradiaphgramatic subarachnoid extension
GPA- CLASSIFICATION:

10. GIANT PITUITARY ADENOMAS
Alleyne et al (2002) –
➢ Type A- SS extension with dumb-bell configuration
➢ Type B- Asymmetric SS extension in sagittal plane anteriorly
➢ Type C- Asymmetric SS extension in sagittal plane posteriorly
➢ Type D- Asymmetric SS extension in coronal plane into the middle fossa
GPA- CLASSIFICATION:

11. GIANT PITUITARY ADENOMAS
Local mass effects Endocrinopathy
Visual deficits Acromegaly
Headache FA syndrome
Hypopituitarism CS
Seizures
FND
CN palsies
Extension into the sph sinus-
Extension into the nasopharynx
CLINICAL FEATURES:

12. GIANT PITUITARY ADENOMAS
Hormonal assessment:
➢ Non- functioning- MC
➢ Prolactinomas- MC functioning GPA
➢ GH secreting adenomas
➢ ACTH secreting adenomas

13. GIANT PITUITARY ADENOMAS
CT Scan –
Detailed information about the bony involvement and tumor calcification
➢ Homogenous with increased attenuation or mixed high or isodense
attenuation
➢ Enhances after IV contrast
➢ Occasionally, low attenuation/ nonenhancing areas inside the lesion –
cystic/ necrotic changes
➢ Absence of perilesional edema (more common in SS meningiomas)
RADIOLOGICAL FEATURES

14. GIANT PITUITARY ADENOMAS
MRI –
Best technique to assess the tumor extent
➢ Variable findings- depend on the presence of infarction, necrosis, cyst
formation, hemorrhage or calcification
➢ Typically, hypo-iso on T1WI ; Iso- hyper on T2WI
➢ Figure of 8 appearance
➢ Mild to moderate heterogeneous contrast enhancement
➢ More invasive than PA- invade the skull base, PNS, ACF or MCF
➢ Displace/ encircle rather than constrict the vessel
➢ Helpful in determining the consistency of the tumor preoperatively- 70% of
the fibrous tumors are iso on T2

15. GIANT PITUITARY ADENOMAS
The main difference from small PA-
➢ High prevalence of macrocysts
➢ More invasive behavior
➢ Mass effect
Features indicating the presence of GPA:
➢ Infrasellar extension
➢ Absence of calcification
➢ Low signal intensity on T1WI

16. GIANT PITUITARY ADENOMAS
Radiological D/D:
➢ Craniopharyngiomas
➢ Meningiomas
➢ Germ cell tumors
➢ Fungal granuloma
➢ PNS neoplasms
➢ Chordoma
➢ chondrosarcoma

17. GIANT PITUITARY ADENOMAS
Craniopharyngiomas:
➢ CT – heterogenous density mass centered in the SS region/ cysts/
calcification at the cyst margins. Solid part enhances on contrast
➢ MRI – hypo (serous content)/ hyper (machine oil - more common) –
Intense cyst on T1WI. Calcification – signal dropout
➢ Large SS mass with a variety of components and extensions – CP likely

18. GIANT PITUITARY ADENOMAS
Meningiomas:
➢ CT - iso/ hyperdense extraaxial lesion, well marginated, intensely and
homogenous enhance . Broad based dural attachment. Calcification-
clumpy,amorphous/ diffuse (psammomatous). Bony erosion +
➢ MRI – iso to hypo on T1WI; iso (50%), hyper (40%) and hypo (10%-
fibrotic/Ca ) on T2WI . Dural tail. Enhance intensely. Constrict the vessel
lumen

19. GIANT PITUITARY ADENOMAS
Chordoma
➢ CT - Destructive, locally infiltrative midline mass expanding the clivus and
breaching the posterior clival cortex. Foci of sequestered bone/irregular
calcification/ destroyed BM
➢ MRI – iso to hypo on T1WI replace the bright BM; heterogenous
hyperintense on T2WI; variable enhancement
Chondroasarcomas:
Radiologically indistinguishable.
Occur laterally, centered on the petroclival suture

20. GIANT PITUITARY ADENOMAS
Fungal granulomas:
➢ CT – low density lesions, enhancement +/-. Perilesional edema. Chronic
abcesses – ring and homogenous enhancement. Paranasal sinusitis. Areas
of bony destruction
➢ MRI – hypointense on T2WI with perilesional edema.

21. GIANT PITUITARY ADENOMAS
➢ Medical
➢ Surgical
➢ Radiotherapy
➢ Radiosurgery
MANAGEMENT

22. GIANT PITUITARY ADENOMAS
➢ Giant prolactinomas- distinctively hyper-responsive
➢ Giant PRLomas- S PRL > 3000 ng/ml/ with invasive growth
➢ 0.5% of all pituitary tumors
DOPAMINE AGONISTS- TOC by many authors
MEDICAL MANAGEMENT

23. GIANT PITUITARY ADENOMAS
First line of treatment except in-
➢ Pituitary apoplexy
➢ Visual deterioration- (several reports indicate equal if not efficacious
improvement on DA agonists)
➢ Resistance / intolerance to medical tt
Dopamine Agonists:

24. GIANT PITUITARY ADENOMAS
DA agonists: Mechanism of action-
➢ Bind to the D2 receptors on the lactotroph membrane- inhibit the synthesis
and release of PRL
➢ Inhibit the proliferation of lactotroph cells in the anterior pituitary- reduce
cellular cytoplasmic volume and tumor size
➢ Involution of the RER and GA – inhibits the PRL synthesis
➢ Reduce the PRL gene transcription and translation
DA reduce the S PRL levels in 75% of the pts with macroPRLomas, reduce
the tumor size by >50% and restore the gonadal function

25. GIANT PITUITARY ADENOMAS
DA – agents used:
➢ Bromocriptine
➢ Cabergoline
➢ Quinagolide
➢ Pergolide
➢ lisuride

26. GIANT PITUITARY ADENOMAS
Bromocriptine: (2 bromo-ergocryptine) – ergot alkaloid
➢ Dosage – 5-20 mg/day TDS
➢ Dose increased gradually- reduces the side effects
➢ S/E: nausea/ vomiting (30%)
numbness/ tingling of toes and fingers
weakness of legs
muscle pains
hypotension
visual and auditory hallucinations
orofacial dyskinesias
erythromalalgia
CSF RHINORRHOEA

27. GIANT PITUITARY ADENOMAS
DA – Problems:
➢ Resistance to treatment – 10-25% of the pts
➢ Intolerance – 5-10% pts
➢ Several reports- use of DA leads to hemorrhage, inflammatory infarction,
increased tumor fibrosis- tumor excision difficult
➢ Not tumoricidal- require lifelong treatment
➢ CSF rhinorrhoea
HENCE THE FIRST LINE OF TREATMENT OF PRL IS STILL
CONTROVERSIAL

28. GIANT PITUITARY ADENOMAS
➢ 5-20% chance of a macroPRLoma to increase in size during pregnancy
➢ No known teratogenic effects of bromocriptine
➢ TO BE CONTINUED DURING PREGNANCY
➢ Long acting depot injection / 28 days – PARLODEL LAR
➢ Slow release oral preparation – PARLODEL SRO
➢ Bromocriptine patch
➢ Per rectal administration

29. GIANT PITUITARY ADENOMAS
Cabergoline:
Long acting DA
Dosage – 0.2-3.5 mg/wk, twice or thrice a wk
Less S/E

30. GIANT PITUITARY ADENOMAS
➢ Transsphenoidal approach
➢ Transcranial approach
➢ Combined TS and TC approach
➢ Complex skull base approaches
SURGICAL MANAGEMENT

31. GIANT PITUITARY ADENOMAS
➢ Regained popularity after Guiot, Hardy and Wiser used it with the advent
of operating microscope and image intensifier
➢ The preferred approach to pituitary tumors by most authors– lesser
morbidity; more direct trajectory
➢ Only recommended by most of the authors in –
lesions confined to the sella
larger lesions with a significant SS extension and
intact diaphgrama
➢ *Goel et al – radical surgery by TS route is indicated and possible in Grade
I-III tumors, while biopsy + RT is the only option for Grade IV tumors
Transsphenoidal Approach:

32. GIANT PITUITARY ADENOMAS
Indications-
➢ Multicompartmental tumors
➢ Large dumbbell suprasellar extension
➢ Large residual tumor/ postoperative hematoma
➢ Uncertain diagnosis
➢ Abandoned TS d/t distorted anatomy
Transcranial Approach:

33. GIANT PITUITARY ADENOMAS
➢ Most of the authors prefer TC route in all the patients – subfrontal/
combined subfrontal- subtemporal route
➢ Primary aim to decompress the intradural portion of the tumor to relieve the
chiasma and hypothalamus- best achieved by attack on the largest
extrasellar part of the tumor by the TC route
➢ Partial excision inadvisable – postoperative pituitary apoplexy

34. GIANT PITUITARY ADENOMAS
Indications-
➢ Dumbbell shaped tumors ( Type A tumors)
➢ Alleyne Type B/C/D tumors
➢ Firm, fibrous tumors
➢ SS extension of the tumors with a prefixed chiasma
➢ In tumors with multiple extensions extradurally or laterally
*Alleyne et al – combined simultaneous TS and pterional craniotomy approach
Combined TS and TC approach:

35. GIANT PITUITARY ADENOMAS
➢ Midline Transfacial approach with osteoplastic maxillotomy and palatal
division and posterior pharyngeal incision (Anson 1995):
Indications-
Large midline tumors with large cranio-caudal extensions and
limited width and cranial base or clival involvement
➢ Lee Fort I maxillotomy approach (Crockard 1993):
Good exposure to middle and upper thirds of clivus but limited in reaching
the tumor superoinferiorly
Complex skull base approaches:

36. GIANT PITUITARY ADENOMAS
Surgical Complications
➢ Poor surgical outcome- mortality 4.2-18% in various series
➢ TS approach less morbid than TC approaches
➢ High surgical mortality d/t: ischemia of the hypothalamus/ brainstem/
cerebral hemispheres; vessel traction; postoperative apoplexy- compression
of vital structures and hydrocephalus

37. GIANT PITUITARY ADENOMAS
➢ General consensus – RT following surgery gives the best results
➢ Various series report – local control rates in macroadenomas of 50-70%
with surgery alone and 80-90% with surgery and RT
➢ Some authors have suggested that the risk of regrowth of the adenomas was
lower than the complications of radiation
➢ Yildiz et al- local control rates and PFS after Sx + RT – 73% and 65%
➢ Goel et al – suggested postoperative RT in Grade II tumors with significant
residual tumor/ Grade III tumors with asymptomatic residual and in all
Grade IV tumors. No RT for Grade I tumors b/c of the ease of surgical
excision
RADIOTHERAPY