Pituitary Adenomas

Chien Wei OMS IV

September 14, 2006

Overview
Background
Clinical Presentation
Classification
Is it beneficial to give RT after
transsphenoidal resection
How much time post-RT should pt. be
followed?
Is there benefit to GKS?
General Management
Complications

Anatomy
60 mg midline structure in sella turcica
Bordered by diaphragma sellae,
tuberculum sellae, dorsum sellae, lateral
sinuses, and sphenoid sinuses
Anterior and posterior lobes

Function
Anterior Lobe:

FSH
LH
ACTH
TSH
Prolactin
GH

Posterior Lobe:

ADH
Oxytocin

Epidemiology
Etiology is unknown
Not associated with environmental factors
10-15% of all primary brain tumors
20-25% of pituitary glands at autopsy found
to have adenomas
70% of adenomas are endocrinogically
secreting
25% of those with MEN-I develop pituitary
adenomas

Natural History
Pituitary adenomas have long natural
history
Vary in size and direction of spread
Microadenomas < 10 mm may cause
focal bulging
Macroadenomas > 10 mm cause
problems due to mass effect

Clinical Presentation
Most common are endocrine
abnormalities hyper-/hyposecretion of
ant. pituitary hormones
HA
Vision changes bitemporal hemianopsia
and superior
temporal defects

Endocrine-Active Pituitary
Adenomas
Prolactin Amenorrhea, galactorrhea,
impotence
Growth hormone Gigantism and
acromegaly
Corticotropin Cushings disease,
Nelsons syndrome post adrenalectomy
TSH - Hyperthyroidism

Non-functioning Adenomas
25-30 % of patients do not have classical
hypersecretory syndromes
May grow to a large size before they are
detected
Present due to mass effect

Visual deficits
HA
Hormone deficiency

Evaluation
MRI
Visual field assessment
Endocrine evaluation

Tests of normal gonadal, thyroid, and adrenal

function
Radioimmunoassays for hormone levels

Classifying
Imaging/surgical classification
Clinical/endocrine functional vs.
nonfunctional
Pathological classification
WHO classification reconciles the three
systems above

Classification
Microadenomas Grades 0 and I
Macroadenomas Grades II to IV
Grade 0: Intrapituitary microadenoma with
normal sellar appearance
Grade I: Nml-sized sella with asymmetric
floor
Grade II: Enlarged sella with an intact floor
Grade III: Localized erosion of sellar floor
Grade IV: Diffuse destruction of floor

Classification
Type A: Tumor bulges into the chiasmatic
cistern
Type B: Tumor reaches the floor of the 3 rd
ventricle
Type C: Tumor is more voluminous with
extension into the 3rd ventricle up to the
foramen of Monro
Type D: Tumor extends into temporal or
frontal fossa

Pathologic Classification
Benign or malignant
Chromophobic Non-functioning
Basophilic Cushings
Acidophilic - Acromegaly
Mixed

WHO Classification
Five-tiered system

Clinical presentation and secretory activity

Size and invasiveness (e.g. Hardy)
Histology (typical vs. atypical)
Immunohistologic profile
Ultrasturctural subtype

The long-term efficacy of conservative

surgery and radiotherapy in the control
of pituitary adenomas
Retrospective study of 411 patients
treated with EBRT for pituitary adenomas
Goal is to assess both long-term efficacy
and toxicity of conservative surgery and
RT in the management of pituitary
adenomas

M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Method
252 of 411 pts with non-functioning pituitary
adenomas
131 of 411 pts had functional pituitary adenomas
(62 acromegaly, 60 prolactinomas, 7 Cushings,
1 TSH, 1 Gn secreting)
338 had surgical intervention; 11 with complete
resection
187 transfrontal approach, 24 trans-sphenoidal
approach, 35 had no surgery
Median f/u of 10.5 yrs
M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Radiation Therapy
Post-op RT to prescribed dose of 45-50
Gy in 25-30 fxs delivered at 1.8Gy/fx
Three-field technique aimed at a target
volume encompassing the tumor and a 12cm margin
Patient treated in supine position

M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Results
Years after RT

Progression free survival

96%

10

94%

20

88%

M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Results
Extent of surgical resection did not correlate with
outcome
Relative risk of death compared with normal
population was 1.76 (p<0.001)
No prognostic factors for survival were identified
Morbidity of RT was low
1.5% of pts had assumed radiation induced
visual deterioration
Cumulative risk for 2nd brain tumor at 20 yrs was
1.9%
M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Conclusions
High tumor control rate and low toxicity in
nonfunctional pituitary adenomas
suggests that limited surgical approach
and post-surgical conventional
fractionated EBRT should be the
treatment of choice

M. Brada et al, Clinical Endocrinology (1993) 38, 571-578

Results of surgery and irradiation or

irradiation alone for pituitary
adenomas
Retrospective review of all patients with
pituitary adenoma treated with RT alone,
surgery and RT, or RT following surgical
failure

Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Methods
212 patients with pituitary adenoma
underwent treatment between 1954 and
1982
Median f/u was 11.9 yrs
Radiologic evaluation consisted of skull
films, angiography,
pneumoenchephalography,
ventriculgraphy, CT and MRI
73% had transfrontal approach
Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Radiation Therapy
RT

Number of Patients

Orthovoltage X-rays

12

Cobalt 60

4 MV X-rays

13

18-25 MV X-rays

175

Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Radiation Therapy
Most patients treated with parallel-opposed
portals
Mean field sizes: 32.1 cm2 for EBRT alone, 45.3
cm2 for surgery and EBRT, and 40.3 cm2 for
EBRT for surgical failures
Median dose for all patients is 4967 cGy
Pts receiving EBRT only had a mean dose of
3989 cGy; post-op EBRT 4493 cGy, and 4553
for EBRT salvage of surgical failures
Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Conclusion
Overall survival after treatment for all
patients is not significantly different from
an age, sex, and race matched population
Patients receiving surgery and post-op RT
had a greater control of local disease
EBRT salvage of surgical failures is
possible
EBRT treatment results in a low
complication rate
Grigsby et al, J of Neuro-Oncology 6: 129-134 (1988)

Gamma-Knife Radiosurgery

Gamma knife radiosurgery for

pituitary adenomas
Retrospective review of 79 pts treated with
GKS for pituitary adenomas
Purpose: To look at the clinical results of
GKS and both its efficacy and safety in
treatment of pituitary adenomas

Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

Methods
79 of 108 pts treated between 1993 to
1999 with GKS whom f/u exceeded 6 mo.
56 FAs ( 29 acromegaly, 15
prolactinomas, 12 Cushings) and 23
NFAs
Mean age 50.2 yrs (26 y/o 82 y/o)
49 female and 30 male
Mean tumor vol. 7.1 cm3
Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

Radiosurgical Treatment
40 pts (24 FAs and 16 NFAs) underwent
pre-GKS surgical resection
Mean margin dose 22.5 Gy (FA 24.2 Gy,
NFA 19.5)
Highest possible isodose (50-70%) used
Mean f/u period of 26.4 months
Tumor control= decreasing or unchanged
tumor vol.
Endocrinologic improvement=fall in elev.
hormone level
Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

Results
Tumor control 93.6% (NFA 95.6%, FA
92.8%)
Tumor shrinkage 24.1% (NFA 26.1%, FA
23.2%)
Endocrinological improvement 80.3%
Endocrinological normalization 30.3%
5/6 pts with preexisting visual field showed
improvement
3 pts. developed complications
Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

Conclusion
Tumor growth control results achieved
with GKS is similar to those for
fractionated RT
GKS may produce better results than
conventional RT in tx of pituitary adenoma
produced endocrinopathies
GKS seems to be safer than fractionated
RT in terms of complications
Masahiro et al, J of Neurosurgery (Suppl 3) 93:19-22,2000

Pituitary Adenoma: The efficacy of RT

as the sole treatment
Retrospective study of 29 patients with
nonfunctional or prolactin secreting
macroadenomas
Tumor dose 4500 cGy in 4-5 wks
Tumor controlled in 93% of pts
Conclusion: RT is effective for improving vision
and can normalize hyperprolactinemia
Doses need not exceed 4500 cGy in 25 fxs

Rush SC, Newall J., Int J Radiat Oncol Biol Phys 1989; 17:165

General Management
Pituitary adenoma management is complex
and is dictated by size, symptoms, and
character of tumor
Treatment options require multiple
modalities, including: Surgery, RT, SRS,
and medical management

General Management
Multidisciplinary approach
Goals:

Define tumor extent

Evaluate hormone activity
Remove tumor mass
Control hypersecretion
Correct endocrine deficiencies

General Management
Microadenomas: transsphenoidal surgery
or RT
Macoradenomas: initial surgery with postop RT
Medical Management

Bromocriptine
Somatostatin

Treatment Algorithm
Pre-treatment MRI
Close to
Chiasm?
yes
Visual field
testing
Deficit
yes
Surgery

no
Surgery
EBRT

no
Surgery
EBRT
SRS/gamma-knife

Appropriate for GKS

Contraindication for GKS

RT Dosing Guidelines

Nonfunctioning
tumors
Functioning
tumors

EBRT
(1.8Gy/fx)

Radiosurgery
(optic chiasm
dose < 9 Gy)

Local
Tumor
Control

Biochemical
Control

45-50.4
Gy

12-24 Gy
to margin

95%

NA

45-54 Gy

25-30 Gy
to margin

9095%

33-95%

Complications
Hypopituitarism
Vision loss
Carcinogenic
Radiation necrosis
Cerebral Infarction

Future Directions
Profiles of toxicity in the 2-D vs. 3-D era

Thank You
Faculty
Residents