Classification of pitutary tumor & their management

CLASSIFICATION OF PITUTARY
TUMOR & THEIR MANAGEMENT
By
Dr.Anand kumar Jha
RIMS RANCHI

Tumor in the sellar and parasellar regions constitute
12-15% of all brain tumors
The most common of these are pitutary tumours,which
constitute 8-12% of all intracranial neoplasms
 Incidentalomas or lesions of the pituitary, picked up by
imaging in assymptomatic patients, have been reported in
10-37% of patients and on a follow up,40% of these
increased in size ,20% become symptomatic and 9% of
these incidental tumours developed apoplexy.
 Most primary pituitary tumours are benign adenomas
which arise from the anterior pituitary gland.
 Neurohypophyseal tumors are rare

CLASSIFICATION OF PITUTARY TUMOURS
 Adenomas may be classified by a number of schemes,
including by endocrine function(aided by immunostaining)
by light microscopy with routine histological staining, and
by electron microscopic appearance.
Microadenoma: A pitutary tumour <1cm diameter.
Macroadenomas: A pitutary tumours >1cm diameter.

Light microscopic
chromophobe: may produce
prolactine,GH,or TSH
Acidophil:produce prl,TSH or
usually GH
Basophil:gonadotrophins,
b-lipotropin,or usually ACTH
Based on secretory products
Endocrine-active tumours: these are classified
based on their secretory products
• prolactin cell adenoma

•Prolactin cell adenomas
sparsely granulated
densely granulated
•Growth hormone cell adenomas
sparsely granulated
densely granulated
•Mixed prolactin cell-growth hormone cell adenomas
•Acidophilic stem cell adenomas
•Mammosomatotroph cell adenomas
•Corticotroph cell adenomas
sparsely granulated
densely granulated

•Gonadotroph cell adenomas
•Thyrotroph cell adenomas
•Plurihormonal adenomas

Endocrine-inactive(nonfunctional) tumours
A. null cell cytoma
B. oncocytoma
C. gonadotropin-secreting adenoma
D. silent corticotropin secreting adenoma
E. glycoprotein-secreting adenoma

MANAGEMENT OF PITUTARY
TUMOR
Hormonally inactive macroadenomas
due to poor response rates to medication, surgery and /
or XRT are usually the initial treatment of choice
Medical management
Bromocriptine
Octreotide
Surgical management
surgical indications for hormanally inactive tumors:

•Tumors causing symptoms by mass efects
•Macroadenomas that elevate the chiasm
•Acute and rapid visual or other neurologic
deterioration.
•To obtain tissue for pathological diagnosis in
questionable cases
• Nelson’s syndrome

PROLACTINOMAS
Prolactin level<500ng/ml: PRL may be normalized with
surgery
Prolactin level >500ng/ml:the chances of normalizing PRL
surgically are very low
Medical management
Dopamine agonists
bromocriptine :start with 1.25mg PO q hs. Add additi-onal
2.5 mg per day as necessary(based on PRL le-vels),
making a dosage change every 2-4 weeks
for microadenomas,or every 3-4 days for macroadeno-mas
causing mass effect.

Cabergoline:start with 0.25mg PO twice weekly,and
increase each dose by 0.25mg every 4 weeks
as needed to control PRL(maximum of 3mg)
Pergolide : Start with 0.05mgPO q hs,and increase by
0.025-0.05 mg(up to a maximum of 0.25mg/
day) until desired PRL levels are achieved.
Response to medical treatment:
treatment response to DA is assesed with
serial prolactin levels as shown in table

Recommendations:
if response to DA is
PRL
Recommend
satisfactory ,treat for
level(ng/ml)
ation
1-4 years
<20
Maintain
adenomas that are not
20-50
Reassess
longer visible on MRI
dose
are candidate for DA
>50
Consider
agonist withdrawal.
surgery
for microadenomas discontinue the drug;
for macoadenomas slowly taper the drug then discntinue
Recurrence rate is highest during 1st year check prolactin
levels and clinical symptoms every 3 months during the
1st year. Long term follow up is required, especially for
macroadenomas.

pe of adenoma Secretion Staining Pathology Percentage of hormone production cases
lactotrophic adenomas(prolactinomas) secrete prolactin acidophilic
galactorrhea, hypogonadism,amenorrhea, infertility,
and impotence
30%[11]
somatotrophicadenomas secrete growth hormone (GH) acidophilic acromegaly in adults; gigantism in children 15%[11]
corticotrophicadenomas secrete adenocorticotropic hormone (ACTH) basophilic Cushing's disease
gonadotrophicadenomas
secrete luteinizing hormone (LH), follicle-stimulating
hormone (FSH) and their subunits
basophilic usually doesn't cause symptoms 10%[11]
thyrotrophic adenomas(rare) secrete thyroid-stimulating hormone (TSH) basophilic to chromophobic
occasionally hyperthyroidism,[12] usually doesn't cause
symptoms
Less than 1%[11]
null cell adenomas do not secrete hormones may stain positive forsynaptophysin 25% of pituitary adenomas are nonsecretive[11]

Type of adenoma Secretion Staining Pathology Percentage of hormone production cases
lactotrophic adenomas(prolactinomas) secrete prolactin acidophilic
galactorrhea, hypogonadism,amenorrhea, infertility,
and impotence
30%[11]
somatotrophicadenomas secrete growth hormone (GH) acidophilic acromegaly in adults; gigantism in children 15%[11]
corticotrophicadenomas secrete adenocorticotropic hormone (ACTH) basophilic Cushing's disease
gonadotrophicadenomas
secrete luteinizing hormone (LH), follicle-stimulating
hormone (FSH) and their subunits
basophilic usually doesn't cause symptoms 10%[11]
thyrotrophic adenomas(rare) secrete thyroid-stimulating hormone (TSH) basophilic to chromophobic
occasionally hyperthyroidism,[12] usually doesn't
cause symptoms
Less than 1%[11]
null cell adenomas do not secrete hormones may stain positive forsynaptophysin 25% of pituitary adenomas are nonsecretive[11]

ACROMEGALY:
 Surgery is the primary t/t modality when t/t is indicated
 assymptomatic elderly patients do not require t/t
if no contraindications, surgery is currently the best
initial therapy. Surgery is not recommended for elderly
patients
 Medical therapy: reserved for
- patients not cured by surgery
-for those who can’t tolerate surgery
-for recurrence after surgery or XRT
 XRT: for failure of medical therapy.not recommended as
initial t/t

MEDICAL THERAPY
Dopamine agonists(DAs): if responsive DAs are
especially well suited for GH tumors that cosecrete PRL
bromocriptine 20-60mg/day ,maximal dose is 100mg/dy
cabergoline
pergolide
others : lisuride, depo-bromocriptine
Somatostatin analogues
as initial medical therapy,or if no response to Das
Octreotide& octreotide-LAR start with 50-100ugSQ q 8h
Lanreotide
GH antagonist:
Pegvisomant 5-40 mg/daySQ
Combination therapy: pegvisomant or octreotide
plus DAs if no response to 1 drug alone

CUSHINGS DISEASE:-
If pituitary MRI shows a mass: trans-sphenoidal surgery
If pituitary MRI is negative perform IPS sampling
if IPS sampling is positive: surgery
if IPS sampling is negative : look for source of ACTH
If biochemical cure is not obtained with surgery:
consider re-exploration if pituitary source is still suspected
stereotactic radiosurgery or medical therapy
adrenalectomy in appropriate patients
Transsphenoidal surgery
it is the t/t of choice for most
cure rates are 85% for microadenomas, but are lower for
larger tumors.

Stereotactic radiosurgery
often normalizes serum cortisol level s. Useful for recurre-nce
after surgery, inaccesible tumors(eg. cavernous sinus)
Adrenalectomy
total bilateral adrenalectomy corrects hypercortisolism
in 96-100% but lifelong corticoid replacement are
required and up to 30% develop Nelson’s syndrome
Medical therapy
for patients who fail surgical therapy or for whom surgery
cannot be tolerated , medical therapy and/or utilized .
Ketokonazole start with 200mg PO BID , usual maintenance
doses 400-1200mg daily in divided doses
Aminoglutethimide 125-250 mg PO BID .do not exceed
1000mg/day

Metyrapone; 750-6000mg/day usually tid with meals
Mitotane: 250-500mg PO q hs
Cyproheptadine: 8-36mg/d divided TID
Thyrotropin(TSH) secreting adenomas:-
transsphenoidal surgery has been the traditional first line
treatment .these tumour may be fibrous and difficult to
remove
for incomplete resection :post op XRT is employed
if hyperthyroidism persists: medical therapy is added
with agents including octreotide ,bromocriptine and oral
cholecystographic agents eg.iopanoic acid
Medical therapy
Octreotide ; start with 50-100ugSQ 8hrs

RADIATION THERAPY FOR PITUTARY ADENOMAS
 Conventional EBXRT usually consists of 40-50 Gy administered
over 4-6 weeks .
 Radiation therapy should not be routinely used following surgical
removal. Follow patients with yearly MRI. Treat recurrence with
repeat operation .
 Consider radiation if recurrence cannot be removed and tumor
continue to grow. Table: Recurrence rate of pituitary
tumors removed by transsphenoi-dally
Extent of
removal
Post op XRT Recurrence
rate
subtotal no 50%
Gross total no 21%
subtotal yes 10%
Gross total yes 0

Surgical Treatment for pituitary adenomas:
 Medical preparation for surgery
stress dose steroids: given to all patients during
and immediately after surgery
hypothyroidism: ideally , hypothyroid patients
should have>4 weeks of replacement to reverse
hypothyroidism
*donot replace thyroid hormone until the adrenal
axis is assesed; if hypoadrenal, begin cortisol
replacement first, may begin thyroid hormone
replacement after 24 hrs of cortisol
Surgery is done frequently on patients with hypo
thyroidism and appears to be tolerated well in d
vast majority of cases

Surgical approaches
• Trans sphenoidal:
usually the procedure of choice.
indicated for microadenoma, macroadenomas without
significant extension laterally beyond the confines of
the sella,patients with csf rhinorrhea, and tumors
extension into sphenoid air sinus
A. sublabial
B. trans-nares
• Trans ethmoidal approach
• Trans cranial approaches;
Indications:-
1.minimal enlargement of the sella with a large supra
sellar mass.
2. extrasellar extension into the middle fossa i,e
larger than the intrasellar component.

3. Unrelated pathology may complicate a trans sphenoidal
approach : rare ,eg a parasellar aneurysm
4. unusually fibrous tumor that could not be completely
removed on a previous transsphenoidal approaches
5. recurrent tumor following a previous transsphenoidal
resection
B. Choices of approach
• Subfrontal: provide access to both optic nerves
• Frontotemporal:( pterional): good access for tumors with
significant lateral extrasellar extension
• Subtemporal: usually not a viable choice. Does not allow
total removal of intrasellar component

TRANS SPHENOIDAL SURGERY
• Position:- supine, horseshoe head rest
or pin headholder
• Equipment:
Microscope
C-arm
image guided navigation system
Endoscopy cart
• Instrumentation: usually includes speculum, curetts
long instruments including bipolars

• Some surgeons use ENT to perform the approach and
• closure and for follow up
• post op ICU
• consent
TECHNIQUE
• Lumbar drain: may be used with some macroadenomas to
inject fluid to bring the tumor down ,also may be use for
p post-op CSF drainage following transsphenoidal repair of
Csf fistula
• Medications: introperatively 100mg hydrocortisone IV q8hrs
• Positioning:
elevate thorax 10-15 degree reduces venous pressure
shoulder-roll

Top of head canted slightly to left
Extended neck slightly
ET tube positioned down and to patients left
Microscope: observer’ eyepiece on the left
• Abdomen or right thigh is prepped for fat graft
• C-arm fluoro
• After approach to floor of sella is complete outline, complet
outline the upper and lower boundaries of sella using an
instrument under C-arm
•Opening the sellar floor:
open exactly in midline using the nasal septum as a land-mark
use a Kerrison rongeur to expand the opening
*stay away from the extreme lateral sella to avoid entering
the cavernous sinus or injuring the carotid artery

•Coagulate the dura centrally in an X pattern with bipolar
cautery
•Consider aspirating through dura with a 20 gauge spinal
needle to rule out large venus sinus,aneurysm or empty
sella
• Incise the dura in the X pattern
• Tumor removal
Macroadenoma:
gently bring tumor into the field with ring curettes and
remove with pituitary rongeurs or aspirate with suction
Microadenoma:
If the side of the tumor is known , begin exploration of
the gland on that side by making incision with #11blade
and using a dissector to try and locate the tomor

•After removal of macroadenoma , check depth of tumor bed
on fluoro or image guidence, and make sure it correlates
with approximate tumor volume on MRI
• The sella may be packed in a number of ways
- place muscle or fat in defect within sella
- recreate the floor of the sella using nasal cartilage placed
within the sella
- pack sphenoid sinuse with fat from abdomen
-fibrin glue may optionally be used to help hold any of
these components in place

Intra operative disasters:
• entry into carotid artery
• opening through the clivus and erroneous biopsy of the
pons
• opening through the floor of the frontal fossa with
into inferior frontal lobes
Perioperative complications
1. hormonal imbalance
acute post-op concerns
alterations in ADH
cortisol deficiency-hypocortisolism-Addisonian
crisis
longterm: hypopituitarism
TSH deficiency

Adrenal insufficiency
Deficiency of sex hormones
2.Secondry empty sella syndrome
3.Hydrocephalus with coma
4. Infection
pituitary abscess
meningitis
5. CSF rhinorrhea
6. Carotid artery rupture
7.Entry into cavernous sinus with possible injury of any
structure within
8. Nasal septum perforation

Perioperative management
Pre-op orders
- Polysporin oinment applied in both nostrils the night
before surgery
- Antibiotics;
chloramphenicol 500mg IV at 11PM& 6AM
or chloramphenicol 500 po at MN & iv at 6 AM; ampicillin
1gm PO at MN &IV at 6 AM
Ampicillin1 gm+0.5 gm sulbactum IVPB at MN &6 Am
-Steroid :- hydrocortisone sodium succinate 50mg im at
11PM & 6AM
Or hydrocortisone 100 mg PO at MN &IV at 6 AM
- Intra op: continue 100 mg hydrocortisone IV q8 hrs
l

Post-op Orders:-
1. intake and out put q 1 hr; urine specific gravity q 4 hrs
and anytime urine output >250ml/hr
2. activity: BR with HOB @30 degree
3.diet: ice chips PRN .patient is not to drink through straw
4. no incentive spirometry
5. IVF: base IV D5 ½ NS +20meq Kcl/L at rate of 75-100ml
per hour
plus replace UO > base IV rate ml for ml with ½ NS
6. Medicins:
Antibiotics: continue chloramphenicol 500 mg IVPB q
6hrs; change to PO when tolerated
Steroid: hydrocortisone 50mg IM/IV q 6 hrs , on
POD #2 change to pednisone 5mg po q 6hrs
for 1 day, then 5 mg PO BID, D/c on POD#6

Diabetes Insipidus:
Criteria: U.O >250ml/hr for 1-2 hrs and SG <1.005
If DI develops , attempt to keep up with fluid loss with IVF
if rate is too high for IV or PO replacement ,check urine SG
and if<1.005 then give a vasopressin preparation
5U aqueous vasopressin (pitressin) IVP/IM/SQ q 6 hrs
OR
Desmopressin (DDAVP) injection SQ/IV titrated to UO.
usual adult dose : 0.5- 1 ml daily in 2 divided doses
THEN: when nasal pack out , either
intranasal DDAVP(100ug/ml) ;0.2 ml BID
OR Clofibrate 500mg PO QID
7. Labs: renal profile with osmolarity q 6hrs 8 AM serum
cortisol
8. Nasal packs :remove on post-op day 3-6

Urinary out put: patterns of post op DI
Post op DI generally follows one of three patterns
1. Transient DI: lasts until 12-36hrs post op
2. Prolonged DI: lasts months, or may be permanent
3. Triphasic response
DI – normalisation or SIADH like picture – DI again
Assesment for post op ACTH reserve
If patient was not hypocortisolemic pre op:
taper and stop hydrocortisone24-48 hrs post-op.Then
check 6AM serum cortisol level after discontinuing
hydrocortisone and interpret the results as shown in
table:-

TABLE:- Interpretation of 6AM cortisol
levels
6AM
cortisol
Interpretati
on
Managemen
t
>9ug/dl Normal No further
tests or t/t
3-9ug/dl Possible
ACTH
deficiency
Place
patient on
hydrocortiso
ne
<3ug/dl ACTH
deficient

Post op CT/MRI scan:
The optimal timing of the initial post-op CT or MRI to
function as a baseline to rule out future recurrence after
trans sphenoidal surgery is 3-4 months post-op.
OUTCOME
Following transsphenoidal surgery
 In cases with compression of the optic apparatus ,there
can be significant improvement in vision following
surgery
 Endocrinogic cure was attained in 25% of prolactin secre
ting tumors, and in 20% of growth hormone secreting
tumors

 Gross total removal was unusual in tumors wiyh>2cm
suprasellar extension
 Recurrence incidence: 12% with most recurring 4-8 yrs
post-op
 Cushing disease: surgical cure rates are 85% for micro-adenomas
but are lower for larger tumors
Management of recurrent pituitary adenomas
 For tumors demonstrating significant regrowth or
symptoms following initial resection, consideration for
re- resection may be given .
 Once the tumor is debulked ,consideration should be
given to XRT, either immediately following the second
operation or, if recurrence after a second operation then
almost certainly after a third debulking

Classification of pitutary tumor & their management

In this document