i hope its useful..!!

1. Pituitary Tumors
Dr. Romi Grover

2. Anatomy
• Hypophysis cerebri.
• Ovoid body situated in the hypophysial fossa
of the sphenoid bone known as sella turcica.
• Weight : 0.8 gm.
• Size : 1.3x1x0.5 cm.

3. Embryology
• Entirely ectodermal in
origin
– Adenohypophysis
• Develops from Rathke’s
pouch
• Upward invagination
– Neurohypophysis
• Develops from the
infundibulum
• Downward extension of
the floor of the
diencephalon

4. Parts
On embryological basis:
 Adenohypophysis (80%)
• Pars infundibularis
• Pars intermedia
• Pars distalis
Neurohypophysis (20%)
• Median eminence
• Infundibular stem
• Infundibular process

5. • Adenohypophysis :
superior Hypophysial
artery: hypophyseal
portal system
• Neurohypophysis :
inferior hypophyseal
artery.
• Hence, Dual circulation.
o Arteries & veins
o Portal venous system

6. Relations

7. Physiology
 Anterior lobe
• Somatotrophs [50%]: acidophilic, GH.
• Lactotrophs : acidophilic, Prolactin.
• Corticotrophs : Basophilic, ACTH, pro-
opiomelanocortin, MSH, endorphins & lipotropin.
• Thyrotrophs : TSH.
• Gonadotrophs : Basophilic, FSH-LH.
 Posterior lobe
• Oxytocin.
• ADH.

8. Epidemiology
• Pituitary tumors are relatively uncommon
• Comprising 10-12% of all intracranial tumors.
• Up to 22% of normal pituitary gland show
adenoma at the time of autopsy
• Most tumour present with in 30- 50 yrs
• 3-7 % under the age of 20 years

9. Etiology
• Unknown
• Genetic factors
MEN-1 syndrome
Autosomal dominant syndrome
characterize by the development of tumour
of pituitary, parathyroid, pancreatic islets
cell
Three% of all tumour arise as a results of
MEN 1
PA develops in 25 %patients with MEN-1

10. Classification
• Pituitary tumors can be classified into three groups
according to their biological behavior:
– Benign,
– Invasive adenoma, and
– Carcinoma.
• Invasive adenomas- may invade into the dura
mater, cranial bone, or sphenoid sinus.
• Carcinomas account for 0.1% or 0.2% of all pituitary
tumors

11. • Based on radiological findings.
– Microadenomas (i.e., the greatest diameter is <10 mm)
corticotrophs, lactotrophs.
– Macroadenomas (i.e., the greatest diameter is ≥I0 mm).
functioning & Non- functioning.
• Most pituitary adenomas are microadenomas.
• Functional criteria- which are used to define tumors in terms
of their endocrine activity in vivo.
– Functional [ acidophilic /basophilic]
– Nonfunctional : [chromophobic]

12. Clinical presentation
Hormone Signs and
symptoms of
hypersecretion
Signs and
symptoms of
hyposecretion
Lab Values
FSH, LH Clinically silent Mood swings,
impotence, vaginal
dryness, hot
flashes,
osteoporosis,
decreased libido
LH, FSH, Serum
testosterone,
Serum estradiol
ACTH Cushing’s disease-
moon facies,
buffalo hump,
puple striae,
hypertension
Weight loss, nausia,
hyponatremia and
hypoglycemia,
hypotension,
fatigue
Serum cortisol
TSH Goiter, moist skin,
tachycardia,
palpitations,
insomnia
Weight gain,
fatigue,
constipation, cold
intolerance,
bradycardia
TSH, free T4

13. Hormone Signs and
symptoms of
hypersecretion
Signs and
symptoms of
hyposecretion
Lab Values
Prolactin Menstrual
irregularites,
infertility,
galactorrhea,
weight gain
Silent Prolactin
GH Acromegaly-
overgrowth, carpal
tunnel,
hyperhidrosis
Dwarfism, fatigue,
osteoporosis,
weight gain
IGF-1, GH

14. • Posterior gland (Neurohypophysis)
– Oxytocin
• Uterine contractions and lactation
– Anti-diuretic hormone
• SIADH-increased water resorption, low sodium
• DI-increased urination, high sodium

15. Disorders associated with the adjacent
compression
• Lateral: Cavernous sinuses : diplopia,
opthalmoplegia, ptosis, diminished corneal
sensation, or facial paresthesias in the upper
face.
• Superior: optic chiasm & hypothalamus.
• Inferior: sphenoid sinus.

16. • Pitutary Apoplexy :
• severe headache
• altered consciousness
• opthalmoplegia
• blindness.
• severe hypopituitarism
• Medical emergency : administration of stress
doses of steroids, fluid , and pain control.
Urgent surgery is also generally warranted to
avoid potential permanent sequelae.

17. Types of Adenomas
• Prolactinomas : 40% to 45% of all pituitary
tumors.
• Women > men.
• Clinical presentation:
Oligo/amenorrhea, galactorrhea, infertility &
androgenization with hirsutism & acne in
women.
Reduced sexual function and libido in men.

18. • Acromegaly : GH hypersecretion
• Source somatotroph adenoma
Ectopic GH/GHRH.
• Insidious nature – delayed diagnosis- macro
adenomas at detection.
• Growth of hands and feet.
• Jaw growth and prognathism
• Hypertrophic cardiomyopathy.
• Sleep apnea syndrome
• Arthropathy, colon polyps
• Carpal tunnel syndrome
• Headache.

19. • Cushing's Disease : overproduction of
glucocorticoids .
• Obesity
• Diabetes mellitus
• Hypertension
• Muscle wasting
• Osteoporosis
• Depression
• Coagulopathy
• cognitive deficits.
• the 5-year cardiovascular mortality for untreated
disease is 50%

20. • Nonfunctioning Pituitary Adenomas :
• Detected incidentally
• Workup of visual field loss, headache, modest
hyperprolactinemia (from compression of the
hypophyseal stalk), or hypopituitarism.

21. Evaluation
• History and physical examination with detailed
neurological examination.
• Comprehensive endocrine evaluation.
 S. Prolactin [ > 200ng/ml]
 Basal GH, IGF-1, glucose suppression, insulin
tolerence, TRH stimulation
 S.ACTH, 24 Hr Urine for 17 OH corticosteroids,
dexamethasone supression test.
ACTH from B/L inf. Petrosal sinuses.
TSH,T3, T4.
FSH, LH, testosterone levels, estradiol levels.

22. • CEMRI brain.
• Neuro-opthalmologic examination with visual
field tests.
• Skeletal survey : acromegaly.

23. Hardy & Vezina Staging System
• Gr I: normal sized sella with possible
asymmetry of the floor.
• Gr II: Enlarged sella with an intact floor.
• Gr III: Localized erosion or destruction of the
sellar floor.
• Gr IV: Diffusely eroded or destroyed floor.
Gr-I & G II – enclosed adenomas.
Gr-III & Gr IV – invasive adenomas.

24. • Therapeutic goals of Pituitary
adenomas Pituitary Adenomas
• Eliminate mass effect and reverse related signs
and symptoms
• Normalize hormone hyper secretion and reverse
secondary effects
• Preserve or recover normal pituitary function
• Prevent recurrence
• Increase survival
• Improve quality of life

25. Management
• Medical
• Surgical
• Radiotherapy

26. Medical
 Prolactinomas :
• Dopamine agonists : Bromocriptine and
cabergoline. 80-90% .
 GH adenomas:
• Somatostatin analogs : octreotide, lanreotide.
• Dopamine agonists: less effective.
• GH receptor antagonist: pegvisomant : daily inj.
 Cushing disease:
• ACTH synthesis/release: cyproheptadine,
bromocriptine, somatostatin, and valproic acid.

27. • Steroid Synthesis Inhibitor: Ketoconazole,
mitotane, trilostane, aminoglutethimide and
metyrapone.

28. Surgery
 Indications:
• Rapidly progressive vision loss.
• Increase in adenoma size despite dopamine
agonists.
• Intolerance or inadequate hormonal response
to medical therapy.
 All symptomatic Pituitary adenomas
TOC is Resection Transsphenoidal
Transcranial

29.  Advantages :
• Hormone levels normalize in 1-12 weeks.
• Mass effects can be decompressed quickly
• Endocrine hypersecretion decreased or
eliminated
• Existing pituitary function retained or improved
rapidly
 Disadvantages:
• Recurrence rate is relatively high with surgery
alone.
B/L adrenalectomy: life long glucocorticoids.

30. Surgical Cure Rate
• Prolactinomas microadenomas-50-60%
macroadenomas-25%.
• GH adenomas : microadenoams- 68%
• macroadenomas-54%
• Cushing syndrome : 57-90%.

31. Radiation Therapy
 Indications :
• Residual surgical tumors
• Medically inoperable tumors.
• Effective for controlling pitutary adenoma
growth & progression.
BUT less effective in normalizing
hormonal activity.
 10 RT: Medically Inoperable.
refusal to surgery.

32. Radiation Techniques
• Conventional Radiotherapy.
• 3D-CRT
• IMRT
• Radiosurgery
 Gamma knife.
 Cyber knife.
• Proton Therapy.

33. Conventional
• Position - supine
• Head and neck flexed
• Head typically held at 450 .
• All patients were treated in a supine position
with flexion of the head so that base of the
skull was in right angle to the couch and
parallel to the central plane

34. 3D CRT
• CECT scan should be obtained.
• When possible, CE MRI should be registered
to the planning CT scan.
• Normal structures to be contoured including
the eyes (lenses), optic nerves, optic chiasm,
brainstem, and temporal lobes.

36. Target volumes
• GTV : pituitary adenoma, including any extension
into adjacent anatomic regions.
• CTV: limited to a 5-mm margin around the tumor
is adequate.
With invasive tumors, Often, the entire
contents of the sella and, if appropriate, the
entire cavernous sinus are included in the CTV.
• PTV : Standard thermoplastic masks are
associated with setup variability of the order of 3
to 4 mm.
A total PTV margin of 5 mm is usually
reasonable.

38. • Typically 5x5 cm field used,
centered on sella

39. XRT Dose Bio. control
1.8Gy/#
Nonfunctioning 45-50.4 Gy 95%
NA
Functioning 50- 54 Gy 90-95%
33-95%

40. Correlation of vision improvement, tumour control with dose of radiation
therapy in 121 patients treated with surgery and XRT
Dose (Gy)
<30 30-39.99 40-49.99 50-54 >54 p value
% with improved visual status 14 29 42 70 0 0.003
% failure 71 25 15 6 0 <0.01
Gringsby et al. Int J Radiat Oncol Biol Phys 1989 ;16:1411

41. SRS
• Dose : 10-27 Gy
• Cranial hard fixation tech
• Adverse CNS event : 38%
• ? Higher response rate.
FSRT
• Conventional doses: 45-50 Gy
• Using re-locatable head frame tech
• Adverse CNS event : 0%

42. • Advantages
– Rapid dose fall off outside the target volume
– Conformality of prescribed dose to the target
volume
– Radiosurgery may provide a more rapid
radiographic and hormonal response than
fractionated radiation therapy
• Different machines use
– Gamma Knife
– LINAC-based systems (X-Knife)
– Cyber Knife

43. Patient selection criteria
• Radio logically distinct adenoma
≤ 3 cm (SRS) or Larger lesions (SRT)
• Contraindications of SRS
– Lesions involved optic apparatus
– Size > 3 cm

44. Proton Therapy
• Rate of energy loss
– Proportional to the square of particle
charge and inversely proportional to
square of its velocity
– As particle slows down rate of energy
loss increases i.e. absorbed dose
increase
– Bragg peak –
– The ability to concentrate dose inside
the target volume and minimize dose
to surrounding normal tissue

45. • Energy -either 155 or 200 MeV depending on
the required beam penetration.
• PTV - all gross visible tumor (or all intrasellar
contents with micro adenomas) with a 5-mm
margin.
• The most common arrangement included 4
fields.
Disadvantages:
• High cost of installation
• Limited utility in other malignancy

46. Late effects
• Late optic neuritis [0.7- 2%]
• 2nd Malignant neoplasms. Royan Marsden
1.3% at 10yrs. Hospital with
1.9% at 20yrs. 45Gy.
• Radiation Necrosis .
• Hypopituitarism [10-30%]
Surgery alone carries lower risk than RT
Radiotherapy alone has lower risk than when
RT and surgery combined

47. Criteria for cure
• Tumor type Criteria
Acromegaly Normalization of IGF-1 levels
Random GH<2.5 ng/ml
GH<1 ng/ml (OGTT)
• PRL PRL< 20 ng/ml
• Cushing’s disease Normal 24 hour UFC

51. Conclusion
• Small organ but critical functions for normal
development, growth, organ regulation,
reproductive regulation, birthing functions.
• Dysfunction – endocrine abnormalities & mass
effects.
• Chronic hypopituitarism – mortality due to
cardiovascular events.
• Cumulative role of medical management &
radiotherapy.
• No change in the quality of life when hormone
deficiencies are suitably replaced.

52. Thank you