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:
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FSH
LH
ACTH
TSH
Prolactin
GH
Posterior Lobe:
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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 – Cushing’s disease,
Nelson’s 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
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Visual deficits
HA
Hormone deficiency
Evaluation
MRI
Visual field assessment
Endocrine evaluation
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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 3rd
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 – Cushing’s
Acidophilic - Acromegaly
Mixed
WHO Classification
Five-tiered system
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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 Cushing’s,
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
5
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 postsurgical 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
8
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 Cushing’s) 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:
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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
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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