management of pitutary tumors Prarabdh JR3

1. MANAGEMENT OF PITUTARY TUMORS
Dr Prarabdh Singh (JR3)

2. FLOW OF MY SEMINAR
 Introduction
 Anatomy
 Clinical Features
 Diagnostic evaluation
 Classification
 Case capsule
 Conclusion

4. CLINICAL FEATURES
4

5. FEATURES OF SELLAR MASS LESION

7. Differential Diagnosis
 Craniopharyngioma
 Pituitary hyperplasia
 Rathke's cleft cyst
 Meningioma
 Germinoma
 Primary CNS Lymphoma
7

8. INVESTIGATIONS

9. Laboratory tests
9

11. RADIOLOGY

12. MRI VS CT
12
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;

13. Dynamic contrast MRI has been proven to be
the best imaging tool in the evaluation of
pituitary adenoma.
3T MRI using T1-weighted magnetization
provides a superior delineation of cavernous
sinus invasion by intrasellar tumors.
Proton MR spectroscopy can be helpful in
differentiating various types of lesions involving
pituitary-hypothalamic axis.
Intraop MRI (IMRI) & intraop realtime USG
during endoscopic pituitary surgery.

14. ACCORDING TO
CLINICAL SYMPTOMS
 Functional
 Non functional
ANATOMICAL SIZE
 Picoadenoma ( < 0.3cm)
 Microadenoma(<1 cm)
 Macroadenoma(>1 cm)
CLASSIFICATION OF PITUITARY TUMOURS

15. 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
15

17. PROLACTINOMA

19. ACROMEGALY

21. CUSHING SYNDROME

23. MANAGEMENT
 Medical/ Observation
 Surgery
 Radiotherapy
23

24. MEDICAL MANAGEMENT

25. 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
25

26. CASE CAPSULE
 A 50 year /F with no comorbidities, No family h/o
malignancy
 c/c blurring of vision since 1 month
 Headache since 1 month
 Evaluated with
 Opthlam : Visual acuity – Rt eye- PL +ve
 Left eye-6/6
 Perimetry- Bitemporal hemianopia
 MRI Brain(P+C) – An homogenously enhancing
lesion of 2x1.8 cm encompassing the sella and also
extending to parasellar region.

27.  Hormone profile:
IGF:54.2
Testosterone:0.47
Cortisol:0.46
T3:1.77
T4:0.57
Prolactin:15.13
U/w TSS in Tmh on 6.10.20
HPR:NFPA

28. Preop scans

29. Post sx scan

30. ROLE OF SURGERY

31. https://doi.org/10.1111/j.1365-2265.2009.03583.x
159 patients
Between 1980 and 2006.

32. Inclusion:
1)Patient who U/w Sx for NFPA
between 1980-2006
2)Histopathologically confirmed
NFPA on basis of lack of
biochemical evidence of
hormonal excess
Methodology:
1)Post op tumor
appearance
a)No residual
tumor:complete tumor
clearence
b)Intrasellar:Confined to
sella
c)Extrasellar:extending
outside sella
Post op imaging at 4-
6months then yearly for
5 years
Recurrence/regrowth
increase in the tumour
remnant size in any
dimension of 2 mm or
more, detected by
imaging with or without
symptom

33. RESULTS
Median F/u post op:5-7years
Presence of Extrasellar tumor
remnant postoperatively was
strongly associated with the risk
of regrowth
Younger age:slightly increase in
risk of regrowth

35. CONCLUSION
 Residual tumour with extrasellar tumour remnant should
undergo prophylactic radiotherapy post-operatively, while
those with complete tumour clearance should be observed
with surveillance MR scans
 Decisions about patients with an intrasellar remnant need to
be individualized based primarily on pituitary status.
 Those with normal or near normal pituitary function may be
followed-up with serial imaging & RT is administered later, if
there are signs of tumour regrowth, while those with significant
pituitary failure should be considered for prophylactic
radiotherapy

36. https://doi.org/10.3171/JNS/2008/108/3/0525
From 1990 to 2005, 585 patients

37. INCLUSION
 Clinical & biochemical absence of hormone hypersecretion &
histopathological confirmation of the tumor.
 Invasive of the cavernous sinus if they corresponded to Grade
3 or 4 in the classification of Knosp & coworkers.
 Tumors intraoperatively interrupting the sellar floor were
considered invasive of the sphenoid sinus.

38. RESULTS
 Residual tumor 173 patients(36.4%).
 Invasion of the cavernous sinus,
maximum tumor diameter, and
absence of tumor apoplexy
associated with unfavorable surgical
outcome.
 Tumors recurred in 83 patients
(19.0%).Younger age at surgery was
associated with a risk of tumor
recurrence.
 In patients with incomplete tumor
removal, adjunctive postoperative
radiotherapy had a marked protective
effect against growth of residual tumor

41. CONCLUSION
 Complete surgical removal of NFPAs can be
achieved in 50% of cases. Surgery is relatively safe
& frequently followed by prompt improvement in
visual symptoms, whereas improvement of pituitary
function is less common.
 Radiation therapy emerged as the most valuable
adjuvant therapy for preventing progression of
residual or recurring tumor.

42. doi:10.1530/EJE-10-0255
A total of 177 patients from 1975 to 2005 were initially included in this retrospective
study

43. INCLUSION
Patient with NFMA diameter >10mm on CT/MRI from
1975-2005.
177patients(21Not operated,10Patients f/u
<6months,only 142 Patients included.
Patients with amenorrhea,galactorrhea & having
decreased libido also included.

44. RESULTS
Mean F/u:6.9years
24%had complete
macroscopic
resection of tumor
had recurrence
47% with surgical
remnant
experienced
regrowth
Overall relapse
rates
5years 25%
10years 43%
15Years 61%
Invasion of the cavernous
sinus, absence of immediate
radiotherapy after the first
neurosurgery, & IHC features of
the tumor (mainly positive
immunostaining for several
hormones or for hormones other
than gonadotropins) were
independent risk factors for tumor
relapse

47. https://doi.org/10.1046/j.1365-2265.2003.01784.x
Between 1989 and 2000, 238 patients were included

48. RESULTS
122 PATIENTS WITH MEAN F/U (12-133MONTHS)
14patients
received post
op RT
Tumor growth:5
Decrease in
tumor size:4
No change:5
108patients
who did not
received RT
Tumor enlargment
:41/78patient with
residual disease
6/30patient
without residual
disease
Cavernous sinus invasion
before surgery & extent of
suprasellar extension in post
op remnant “independent
factor” for tumor
enlargement…

49. Conclusion of
study:
10years PFS 93%(With RT) 47%(Without RT)
Incidence of
recurrence
33%(invasive
tumors)
15%(enclosed
adenoma)

50. 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
50

51. 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
51
Surgery alone – overall
local control rate- 50 to
80%

52. ROLE OF RADIOTHERAPY

53. Aim:Role of RT in local control relative to its complication.
Patients:160 Patients(between 1971-1980)Review focus on
128 patients(T/t with surgery & RT)
Median dose=45Gy
Result:Median f/u8.3years
10Years actuarial local control rate was 87% for entire
160patients & 91% for 128patients.
Conclusion:Post-op EBRT is highly effective in preventing
recurrence of hormonally inactive adenomas
https://doi.org/10.1016/0360-3016(92)90941-A

54. Actuarial tumor control rate for 128
patients receiving surgery and
postoperative RT as initial treatment
(solid line), compared to the 29 patients
treated for recurrence (dashed line).
Actuarial overall survival (OS) and
cause-specific survival (CSS) for the
entire 160 patients

55. Actuarial rates of permanent hypopituitarism due to radiation therapy for
hypothyroidism (solid line), hypoadrenalism (dotted line), & hypogonadism
(dashed line).

56. 148 patients had biopsy-proven or clinically suspected pituitary adenomas treated
with radiation at the University of Florida between March 1965 & November
1993.
https://doi.org/10.1016/s0360-3016(97)00335-0

57. Aim:To review outcomes and treatment sequelae in patients treated with
external beam radiotherapy for pituitary adenomas
Patients:
141Patients received RT and 2year followup
121 had newly diagnosed adenomaT/t with Sx(98)and RT(23)
20Patients had recurrent tumorsSalvage t/t with Sx and RT(n=10) or RT
alone(n-10)
Results:
Young age was predictive of worst outcomes. (p = 0.0354)
Prolactin & ACTH secreting tumors had significantly worse tumor control, as
did patients treated for recurrence
Conclusion: Adenomas well controlled by RT either RT alone or in combo
with Sx.
Tumor control Sx+RT RT alone
At 10Years 95% 90%

59. Aim:To assess long-term tumor control & to identify factors affecting tumor
control such as higher radiation doses, improved imaging, and histological
characteristics of the tumor
Patients:120 patients (90:M,30:F)who received RT for NFPA between 1960
& 1991
Median F/u:9years RT dose varied from 37.6 & 65.6Gy (median is
46.7Gy)
Results:
https://doi.org/10.1046/j.1365-2265.2003.01784.x
Years Tumor progression
10Yrs 87.5%
20Yrs 77.6%
30yrs 64.7%
Conclusion:
a)Tumor progression after
RT(Oncocytoma variant>non
oncocytoma)
b)Dose 40-45Gy is optimal
c)F/u of 20years is needed
for checking adequate tumor
control.

61. CASE CAPSULE-2

62. 29Years female
P.w.c.o coarsening of facial features since 2012
C.O Oligomennorhoea since 2016
C/o headache since 2016 that gradually increased in 2017
Hormone profile:
FSH:4.87
Prolactin:66.38
TSH:0.6926
ACTH:17.99
Basal cortisol:5.63
IGF1:736
MRI Brain :Solid cystic lesion in sellar suprasellar region abutting and
displacing Optic chiasma & ICA
U/w Sublabial rhinoseptal transphenoidal excison on 11.12.2017
HPR:Pitutary adenoma
Imp:Secretory pitutary adenoma

63. Post Surgery
scans

64. ROLE OF RT IN HORMONALLY ACTIVE
ADENOMA???

65. https://doi.org/10.1016/0360-3016(95)00071-6

66. Aim:To evaluate therapeutic outcome and side effect of radiotherapy in pituitary
adenoma.
Materials and methods: Retrospective analysis of 138Pt (74M,64F) irradiated for
adenoma from 1972 to 1991.
Mean age:49.7years
138 Patients
70:NFPA
50:GH adenoma
11:Prolactinoma
7:ACTH adenoma
99PtSxRT
23PtT/t for recurrence of disease
after Sx
16 received RT as mode of T/t
Results:
Tumor control achieved in 131
pt(94.9%)
Dose response relationship in
favor of dose >45Gy
90% patient with hormonally
active adenoma had beneift
Conclusion:
For optimal tumor control 45Gy -
48Gy (conventionally
fractionated ) should be applied

69. Aim:To study control rate after RT in hormonally active adenoma.
Inclusion criteria: (1972-1986)145 patients received RT for hormonally
active adenoma ,Median age:39years
Median F/u :7.3years
Median Dose:50Gy
Results:
RT as primary T/t RT after initial Sx Salvage therapy
17 Patients 65Patients 63patients
PFS at 10years 96%
OS at 10years 86%
CSS at 10years 97%
https://dx.doi.org/10.3857%2Froj.2011.29.3.156

70. Conclusion:
Post op EBRT is highly effective in preventing recurrence of space occupying
effects of hormonally active adenoma
Long term biochemical outcomes improved by adding medical therapy
10Yr actuarial
elevated hormonal
level
RT alone RT+Medical m/m
61% 41%

73. RT IN ACTH SECRETING TUMORS??

74. Between Jan 1980 & June 199382ptUnderwent
TSS30(Pt had recurrent disease after Sxreceived RT
Mean dose of RT was 50+/-1GyReassesment of pitutary &
adrenal function every 6 months post RT
Remission was defined as the regression of symptoms and
signs of Cushing’s syndrome, normal urinary cortisol
excretion, and a low plasma cortisol concentration in the
morning.

75. Result:
83% had remissions during
median followup of 42months
Remission usually occurred in first
2 years
None of the 25 patients had a
relapse of Cushing’s disease after
remission was achieved
Conclusion:
Pituitary irradiation is
an effective and well-
tolerated treatment for
patients with Cushing’s
disease in whom
transsphenoidal
surgery is unsuccessful
Hormone deficiency Number
Growth hormone 17
Gonadotropins 10
Thyrotropins 4
Corticotropins 1

77. 40Patients(12M/28F) with residual/recurrent ACTH secreting pitutary
adenomatreated with RT1989-2002
(34Pt45Gy,) & ( 6Pt50Gy)F/u 3months with MRI
Results PFS 5Yrs->93% 10Yrs93%
OS 5Yrs->97% 10Yrs 95%
Conclusion:
Radiotherapy is effective in long term tumor & hormone hypersecretion
control of ACTH secreting adenoma
“45-50Gy is adequate for tumor control”

79. ROLE OF RT IN GH SECRETING
TUMORS??

80. Objective To evaluate efficacy and safety of radiotherapy on
acromegaly treatment.
Patients:Of 102 acromegaly Patient t/t with RT from 1978 to
2003 99Pt(42M,57F)Retrospectively studied
RT dose: 89pt by 32.4 to 60Gy & 10by stereotactic RT
Mean f/u time after RT was 1-16years
Results:
Hormonal level Percentage
GH<2.5ng/ml 54%
Normal IGF -1level 42%
Normalisation of both 38%

81. Patients:1840patients from 1970-2004 from 14 centres
Objectives:Effect of pituitary irradiation on
a)Lowering of serum GH & IGF-1 level
b)Proportion of patients achieving GH level <2.5ng/ml
& normal age corrected IGF-1
c)Incidence of hypopitutarism
Median administered RT dose:45Gy/25#
Results: 22% of pt achieved a level <2.5ng/ml by
2yrs,60% by 10years, & 70% by 20years
IGF-I levels fell in parallel to those of GH with 63% of
patients having a normal level by 10 yr
Years Fall of GH
2Years 5.3ng/ml
10Years 2ng/ml
20Years 1.1ng/ml
Conclusion:Conventional
irradiation is effective in
reducing GH & IGF-1

82. FOLLOWUP

83. 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%)
84
Perez 7th edtion

84. THANK YOU