MANAGEMENT OF PITUITARY TUMORS

1. DR KIRAN KUMAR
MANAGEMENT OF
PITUITARY TUMORS
1

2. ANATOMY OF PITUITARY GLAND
2
Located at the base of brain
A midline structure resting
in sella turcica, a cavity of
the sphenoid bone .
Also known as hypophysis
cerebri.
Size: 1.3 X 1.0 X 0.5 cm
Weight : 0.55 to 0.6 gm
Relations:
Superior: diaphragm sella
and optic chiasma
Inferior: venous and
sphenoid sinus
Lateral: cavernous sinus
Ant. And post. : sella wall

3. ANATOMY OF PITUITARY GLAND (contd…)
 Pituitary has Anterior and posterior lobe.
 Stalk is made up of neural and vascular
elements, which connects the pituitary to
hypothalamus.
3

4. Epidemiology
4
 Incidence: 10 –15% of all primary intracranial
tumors.
 Gender : overall male : female ratio is ~2 –3:1.
 ~70% are hormone-secreting tumors.
 14.4% of apparently normal pituitary glands removed
at autopsy contain adenoma (metaanalysis- Ezzat et al)
 Age: usually occurs in patients aged 30 –60 years,
with a median age of 52 years

5. Risk factors
 The etiology of pituitary adenoma or
adenocarcinoma is unknown
A genetic predisposition to develop adenomas
has been described in
MEN I syndrome
Carney complex
Isolated familial
somatotropinomas(IFS)
5
Perez 7th edition

6. Pituitary Adenomas
Prolactinomas most frequent.
 Non-functioning adenomas (NFPA) second most
common.
 ACTH and GH adenomas : 10-15 % of all adenomas.
 TSH adenomas very
rare.
Functional adenomas are more
common in women, while
nonfunctioning and GH-
secreting adenomas are more
common in men.
6
Perez 7th Edition

7. Pituitary Adenoma (Natural History)
 Tumor of the pituitary may compress the remainder of
Pituitary gland and may expand the sella , compress
optic apparatus.
 They may erode the walls and extend laterally into
cavernous sinus.
 Tumor may extend into temporal lobe, third ventricle and
posterior fossa.
 Pituitary tumors do not arise in the posterior lobe.
7
Devita 10th edition

8. CLINICAL PRESENTATIONS
 The presenting symptoms may be due to
Hormonal malfunction
Due to local tumor growth and
mass effect.
 Endocrine abnormalities may be a consequence of hyper or hypo secretion of
pituitary hormones.
 Hypopituitarism
 Hyperpituitarism
Cushing’s disease
Hyperprolactinomas
Hyperthyroidism
Acromegaly.
8

9. CLINICAL FEATURES
9
Disease
PROLACTINOMA More common in females
Prolactin hypersecretion
Elevated serum prolactin level
Symptoms include amenorrhea, galactorrhea,
decreased libido, impotence, and infertility
ACROMEGALY Caused by GSH pituitary adenoma
Elevated GH and insulin-like growth factor (IGF-1)
Acromegaly in adults: enlargement of hands and feet,
visual impairment (20% of patients), weight gain
arthritis, organomegaly, heat intolerance, glucose
intolerance
Cushing’s disease Caused by ACTH-secreting pituitary adenoma
More common in females
Symptoms mostly caused by hypersecretion of ACTH:
truncal obesity, hypertension, psychologic changes, skin
striae, diabetes, hirsutism, and Nelson’s syndrome

10. CLINICAL FEATURES
10

11. FEATURES OF SELLAR MASS LESION
 PITUITARY
 Hypopituitarism
 OPTIC CHIASMA
 Bitemporal Hemianopia
 Superior temporal defect
 CAVERNOUS SINUS
 Ophthalmoplegia
 Ptosis
 Diplopia
 OTHERS
 Headache
 Hydrocephalus
 Dementia
11

12. Differential Diagnosis
 Craniopharyngioma
 Pituitary hyperplasia
 Rathke's cleft cyst
 Meningioma
 Brainstem Gliomas
 Glioblastoma Multiforme
 Germinoma
 Ependymoma
 Low-Grade Astrocytoma
 Primary CNS Lymphoma
12

13. DIAGNOSTIC EVALUATION
13

14. Laboratory tests
14

15. DIAGNOSTIC WORK-UP
INV. SERUM
VALUES
ROLE
Prolactin < 20µg/ml > 200 µg/ml
ACTH 9-50 pg/ml Evaluation by dexamethasone
suppression test
TSH 0.4-4 mIU /ml
Growth hormone 1 – 9 ng/ml Evaluation by growth hormone
suppression test
FSH 4.7-21.5
mIU/ml
Endocrine evaluation
15

16. MRI VS CT
16
MRI CT
SENSITIVITY – 100 % ( patel et al) 17 TO 22 %
SPECIFICITY – 91 % ( patel et al ) -
pituitary adenoma : T1 w images isotense
T2w images- hypertense
DISADVANTAGES-
Poor soft tissue imaging
Radiation exposure
High resolution gadolinium enhanced
dynamic MRI – current imaging modality
of choice
Connor SE et al Magnetic resonance imaging criteria to predict complete excision of parasellar pituitary
macroadenoma on postoperative imaging. J Neurol Surg B Skull Base. Feb 2014;75(1):41-6.
Patel KS et al Utility of Early Post-operative High Resolution Volumetric MR Imaging after
Transsphenoidal Pituitary Tumor Surgery. World Neurosurg. Jul 18 2014;

17. Imaging of pituitary tumor
17
MRI images showing
adenoma

18. Contd…
18

19. ANATOMICAL SIZE
 Picoadenoma ( < 0.3cm)
 Microadenoma(<1 cm)
 Macroadenoma(>1 cm)
CLASSIFICATION OF PITUITARY
TUMOURS
PHYSIOLOGICAL
 Ant pituitary
 Prolactin
 Growth hormone
 Adrenocorticotrophic hormone
 Leutinizing hormone
 Follicle stimulating hormone
 Thyroid stimulating hormone
 Post pituitary
 Oxytocin
 Vasopressin
19
ACCORDING TO CLINICAL
SYMPTOMS
 Functional
 Non functional
Perez 7th edition

20. Classification(Cont…)
20
Hardy’s radiographic classification for pituitary adenomas and grading
schema for suprasellar extension

21. PATHOLOGICAL CLASSIFICATIONS
Ant Pituitary has 5 specific cell
types
 Somatotrophs : produces growth
hormone , acidophilic
 Lactotrophs : produces prolactin,
acidophilic
 Corticotrophs : produces ACTH ,
MSH, basophilic
 Thyrotrophs : produces TSH ,
basophilic
 Gonadotrophs : FSH , LH,
basophilic
Post pituitary : pituicytes
21
Perez 7th edition

22. MANAGEMENT
 Medical/ Observation
 Surgery
 Radiotherapy
22

23. Goal of Pituitary Adenoma Therapy
 To remove Tumor
 Control hypersecretion
 Restore lost function without hypopituitarism or injury to
normal tissue
 Surgical resection is the treatment of first choice for
prompt decompression of mass effects and improvement of
pituitary function
 Postop RT is indicated in adjuvant setting
23
Devita 10th edition

24. MICROADENOMAS
MICROADENOMA
Symptomatic YES
NO
Prolactinoma- medical
management
Others- Transsphenoidal
surgery
OBSERVATION
24

25. MACROADENOMAS
MACROADENOMA
( functional or non functional)
Vision
impaired NO
YES
SURGERY vs RT/SRS
(Surgery preferred)
SURGERY
COMPLETE
RESECTION
YES NO
Observation Radiotherapy
Progress on
observation
25
operated

26. OBSERVATION
 In asymptomatic non secreting microadenomas
 Small asymptomatic prolactinomas 2 -4 mm no
testing required 5-9 mm MRI can be done once yearly
 Indications for intervention
 Tumor growth on imaging
 symptoms of hypersecretion
 development of visual field defects
Long term follow up
with MRI and
hormonal assays
26

27. MEDICAL MANAGEMENT
 Modality of choice in prolactinomas
 In others, for suppression of hypersecretion
 For postop./ post RT hypopituitarism.
 For prolactiomas bromocriptine and cabergoline are
equally effective.
 For cushing’s disease medical therapy if surgery/RT
failed.
27

28. MEDICAL MANAGEMENT
Drugs used Response rate/
control rate
Dosage and
schedule ( p/o)
Dopamine agonists (
cabergoline or
bromocriptine) for
prolactinomas
80 to 90% control of
prolactin production
Cabergoline – 0.5 to 1.0 mg
BD weekly
Bromocriptine-0.625-1..25
mg
Duration – life long at low
doses
OCTREOTIDE 50 to 60% control of
growth hormone
50 microgm tid to
1500microgm per day
KETOCONAZOLE 70 to 75% control of
ACTH levels
600 to 1200 mg / day
METYRAPONE 75 % control of ACTH 2 to 4 g/day
AMINOGLUTITHA
MIDE
- 250 mg tid
Harrison 20th edition
28

29. SURGERY
29

30. SURGERY
 Goals of surgery : Decompression and to
normalize hypersecretion , With preservation of
normal pituitary function ( first line
treatment )
 Tanssphenoidal surgery – standard approach,
better and safer than transcranial approach.
 TSS resulting in rapid reduction of tumor, 90%
success if small tumor. Complete resection is
achievable in only 44
to 88 % patients
Devita 10th edition
30

31. Surgery ( contd..)
Devita 10th edition
Surgical
techniques
Results Comments
Transnasal vs
Transseptal
sphenoidal approach
ACTH (86 % vs. 81
%), PRL (89 % vs. 66 %) and
GH (85 % vs. 77 %).
( Control of hormone )
Transnasal
sphenoidal approach
better
Transcranial
approach
- For suprasellar
tumors extending to
middle carnial fossa
31
Surgery alone – overall
local control rate- 50 to
80%

32. TYPES
 MICROSCOPIC TRANSSEPTAL TRANSSPHENOIDAL
 Safe procedure with mortality rate 0.5%
 Contraindications are sphenoid sinusitis,
ectatic midline carotid arteries,
lateral surpasellar extent
32

33. TYPES ( contd…)
 ENDOSCOPIC TRANSNASAL
TRANSSPHENOIDAL
 Allows better visualisation of pituitary gland,
hypophyseal stalk, cavernous sinuses, optic nerve
and suprasellar areas
 TRANSCRANIAL
 Requires craniotomy and retraction of frontal lobes
 Used for large invasive tumors with significant
suprasellar extension
 When transsphenoidal approach is contraindicated
33

34. Risks of surgery:
4.6% post-op neurologic
complication
infarction/hemorrhage
2-10.5% Diabetes Insipidious
8.8% fluid and electrolyte
imbalance
2% Cerebrospinal fluid rhinorrhoea
2% Meningitis
3.2% cranial nerve 3,4,or 6 palsies
Devita 10th edition
34

35. RADIATION THERAPY
35

36. INDICATIONS
36
 Definitive treatment for invasive, inoperable or recurrent
pituitary tumor if optic chiasm is at risk of compression, with no
symptoms.
 Radiation therapy is not to be appropriate for patients with
visual field deficits, because quick and dramatic tumor shrinkage is
not expected
 Adjuvant treatment for large tumors, after incomplete
resection (when MRI at 6 –12 months postoperation demonstrate
residual tumor), or with persistent hormone hypersecretion
( risk of local recurrence after incomplete resection – 33 % to 80 %)
 Not indicated after complete resection of
microadenoma unless with persistently raised hormone levels

37. TECHNIQUES
2 D planning
3 D conformal radiotherapy
( 3 DCRT ) or IMRT or IGRT
Stereotactic Radiosurgery
37

38. MANUAL AND 2D PLANNING
 Positioning
 Supine with neck flexed and
head at 45 degrees
 Pituitary board can be used to
achieve this
 Immobilisation done with
thermoplastic mask
 VOLUME
 The entire pituitary gland with
extensions and a margin of 1-
1.5 cm
38

39. 2 D planning
 PORTALS
 Two parallel and opposite wedged lateral fields and one anterior or
vertex beam that enters above the eyes
 The centre of the pituitary is located at a point 2-2.5 anteriorly to
tragus and 2-2.5 cm superiorly to that point
 Taking this point as centre a field of ( 4x4)cm-(6x6) cm is marked
 ENERGY
 6-10 Mev or Co 60
 DOSE
 Nonfunctioning tumours 45-50.4 Gy@1.8 Gy/#
 Functional tumours 50.4-54 Gy @1.8 Gy/#
39

40. Lateral Simulation Radiograph
40

41. Isodose distribution
41
2 field technique 3 field technique with 45 degree wedge

42. Radiotherapy techniques
2 FIELD TECHNIQUE 3 FIELD TECHNIQUE CONFORMAL
Two lateral opposed
fields should be avoided
in order to decrease the
dose to temporal lobes
An anterior field and two
lateral wedged fields.
Anterior field is
positioned to lie above the
plane of eye and exit
through occiput.
Low dose to temporal
lobes
Using CT planning,
MLCs are used to shape
a superior oblique and
opposing
lateral beams
42

43. Critical structures
Optic nerve – 60Gy
Optic chiasm- 54Gy
Temporal lobe- 45 Gy
Brain Stem- 50Gy
Eyes Lens- 10 Gy
Cornea- 60 Gy
Retina- 45 Gy
43
For SRS – optic
nerve tolerance
8 to 9 G y

44. 3D conformal RT
LINAC IMRT/ Image-Guided
Radiotherapy
Gamma Knife Radiosurgery
Cyberknife
Proton Radiosurgery
TECHNIQUES
44

45. 3D conformal RT
or IMRT
45

46. 3 D CRT or IMRT
 Definition of target volume : CT scans are obtained with 3 mm
slice thickness from the skull vault to the first cervical vertebra with
intravenous contrast, and co-registered with postoperative gadolinium-
enhanced T1-weighted MR images.
GTV
The pituitary adenomas
including any extension
into adjacent anatomic
regions.
Enhancement on T1-
weighted MR images
postoperatively.
(post decompression
changes must be taken
into account.)
GTV
1 to
1.5
cm
CTV
CTV
3mm
PTV
46

47. Contd….
 FSRT is characterised by improved patient localisation, tighter
volume definition more conformal isodose distributions
 It has better safety profile and efficacy
 IMMOBILISATION - Aim is to achieve a patient positioning
error of less than 3mm by various means like
 Invasive halo ring
 Radiocamera bite block
 Non invasive Head frames
• Simulation
47

48. (cont…)
 TARGET VOLUME DELINEATION
 GTV is designed with help of MRI and extent of cavernous
sinus invasion should be included
 CTV= GTV + 1 to 1.5 cm
 PTV:CTV +3 mm margin
DOSE PRESCRIPTION –
 Nonfunctional adenomas : dose of 45 to 50.4 Gy given in 1.8Gy
daily fractions ( 45 Gy/1.8Gy per #/ 5 weeks)
 Functional adenomas : 50.4 to 54 Gy in 1.8 Gy daily fractions
( 54 Gy/1.8 Gy per # / 6 weeks)
48

49. 49

50. 50

51. 51

52. RADIOSURGICAL TECHNIQUES
Gamma knife – 201 Co- 60 sources
Rotating Gamma knife – 30 Co- 60
sources
Cyberknife
Proton radiosurgery
52

53. RADIOTHERAPY TECHNIQUES
 Stereotactic- using a precise 3 D mapping technique to guide a
procedure.
Terms Meaning
SRS ( stereotactic
radiosurgery)
Conformal irradiation of define
target volume in a single
session
SRT ( stereotactic
radiotherapy) or FSRT
Conformal irradiation in
multiple fractions.
FSRS ( fractionated SRS) Treatment in 2 to 5 fractions
PEREZ 7TH EDITION
SRS – GTV is treated with no
added margins
53

54. Dose prescription
SRS
 For non functioning pituitary
adenoma- 16 – 20 Gy
 For functioning pituitary
adenoma- 20-25 Gy
FSRT-
 For non functioning pituitary
adenoma- 45-50.4 Gy @ 1.8 Gy/
#
 For functioning pituitary
adenoma-50.4 – 54 Gy @ 1.8
Gy/ #
54

55. STEREOTACTIC
RADIOSURGERY
General principal for pituitary
adenoma
Tumor target < 3cm
Tumor Distance from optic apparatus > 3 mm
Delivery systems include cyber knife and
gamma knife
55
Perez 7th edition

56. Gamma knife
 Head is fixed with an appropriate stereotactic
head frame and a high resolution imaging study is
obtained
MRI and CT scan images used for gamma knife
Gamma knife uses smallest collimators and
maximum number of isocentres .
The dose to optic chiasma is limited to <8-9 Gy
DOSE
 Non functioning (16-20Gy)
 Functioning (20-25 Gy)
56

57. 57

58. CYBERKNIFE
58

59. CYBERKNIFE
 LINAC attached with a robotic arm
 Frame less technique
 Robotic arm moves around patient and applies real
time adjustments .
 Numerous small beams are used.
 DOSE
 Non functioning (16-20Gy)
 Functioning (20-25 Gy)
59

60. 60

61. Chief advantage is that the beams stop at a depth related
to the beam's energy.
Based on Bragg peak phenomenon
Results are comparable to other techniques
Highly expensive
PROTON RADIOSURGERY
61

62. 62

63. RESULTS
Perez 7th edtion
Surgery alone overall local control rate 50 %TO 80 %
The role of RT is generally in the adjuvant
setting with the following indications: recurrent tumor
after surgery; persistence of hormone elevation after surgery;
residual disease after STR or debulking procedure.
Post op R T increases local control 90 to 100 %
63

64. SRS VS FSRT
1) Incidence of hypopituitarism and optic neuropathies after
SRS is lower.
2) Hormone level normolization is quicker in SRS.
3) overall treatment time is short in SRS.
4) SRS costlier and available at few centres only.
64

65. RESULTS
65

66. Contd…
66

67. FOLLOW UP
67

68. LATE EFFECTS
 Risk of optic nerve or
chiasm injury is dependent
on both the total dose and
dose per fraction.
Optic
neuropathies
(0.7% to 2%)
 doses ranging from 45 to
50 Gy to the whole
pituitary gland carry risk.
Hypopituitarism
(10% to 30%)
68
Perez 7th edtion

69. Contd…
 Secondary brain tumors- relative risk of
developing a second tumor compared with the
normal, unexposed, population was 9.3%.
 Cerebral Infarction
 chronic hypopituitarism also increased mortality
from cardiac and cardiovascular events.
69
Perez 7th edtion

70. SUMMARY
NON AFFORDABLE PATIENTS AFFORDABLE PATIENTS
Post operation – conventional
fractionation therapy
Dose range – 45 to 54 Gy @ 1.8 Gy
per fraction
Benefit – local control 90 to 95 %
Radiotherapy machines- Co – 60
Duration : 5 to 6 weeks
Two options-
A) if tumor size < 3 cm and distance
from optic apparatus is 2 to 3 mm
SRS is preferred
Local control with SRS- 90 to 100%
Duration – single sitting
B) If tumor size > 3cm and distance
from optic apparatus is < 2mm then
go for FSRT
70

71. Thank you
71
Reference:
1.Perez and Brady's Principles and Practice of Radiation Oncology.7th edition.
2.DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of
Oncology.10th edition.
3.Harrison Principles of Internal Medicine 20th Edition.
4.Decision Making in Radiation Oncology.