Pituitary tumor accounts for ~10% ICT. They are common in 3-4 decade and shows association with MEN I. About 5% of PT are invasive usually with giant tumor (>4cm). Tumor can be classified as functional (hormone secreting) or non functional. This slides details the algorithmic approach in management of pituitary tumors.

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DR. SURESH BISHOKARMA
MS, MCH (NEUROSURGERY)
Department of Neurosurgery,
Upendra Devkota Memorial National Institute of Neurological and Allied Sciences
Bansbari, Kathmandu
PITUITARY ADENOMA

2.  Hermann Schloffer performed the first transsphenoidal resection of a pituitary tumor in
1907.
 Harvey Cushing popularized it in the two decades afterward.
HISTORY

3.  Two lobes: Adenohyophysis and Neurohypophysis.
 Normal AP diameter of pituitary gland: female of childbearing age (≈ 13–35 yrs): ≤11
mm, for all others normal is ≤9 mm. (Note: pituitary glands in adolescent girls may be
physiologically enlarged (mean height: 8.2 ± 1.4 mm) as a result of hormonal stimulation
of puberty.
 Anterior can be divided into the pars tuberalis (pars glandularis) and pars distalis (pars
glandularis) that constitutes ~80% of the gland.
 The pars intermedia (the intermediate lobe) lies between the pars distalis and the pars
tuberalis.
 Posterior lobe is connected to hypothalamus by stalk via median eminence and has high
signal on T1WI (phospholipids).
 Absence of this “bright spot” often correlates with diabetes insipidus as may occur with
autoimmune hypophysitis.
INTRODUCTION

4.  Development: 4th week: Primitive stomodeum and Neuroepithelium of hypothalamus
toward sella.
 Vascular anatomy:
 Arterial supply:
 Ant. pituitary is supplied by superior hypophyseal artery. Post pituitary by SHA,
IHA and infundibular artery. Capsule: McConnel (C4 branch)
 Portal venous plexus around the hypothalamopituitary complex for route of
hormonal influence by hypothalamus
 Venous drainage by inferior hypophyseal vein.
DEVELOPMENT AND VASCULARITY

5.  Anterior pituitary (5 cells=6 hormone also folliculostellate (FS) cells).
 Posterior pituitary (2H)
 MSH is synthesized in AP and stored by intermediate lobe (aka intermedin).
 TSH producing tumor can itself elevate prolactin.
 Hormones in posterior pituitary is secreted in magnocellular neurosecretory cells of
supraoptic and paraventricular nucleus of hypothalamus and carried via stalk along the
infundibulum to store in PP ready to release
TYPES OF CELLS IN ANTERIOR PITUITARY

6. Cellular Composition of gland

7. CLASSIFYING PITUITARY TUMOR
Most common pituitary tumor is non-functional tumors

8.  Accounts for ~10% ICT. 3-4 decade, MEN I.
 About 5% of PT are invasive. Giant >4cm.
Epidemiology

9. 1. HORMONAL SYMPTOMS 2. MASS EFFECT 3. APOPLEXY 4. INCIDENTAL
1. Hormonal symptoms: Hypersecretion or hyposecretion.
 68% of adenoma secrets hormones (Prl (48%)> GH (10%), ACTH (10%), TSH(1%).
 Underproduction: Mass effect by non functioning or functioning tumor (GH>Gonadotropins>
TSH> ACTH). Chronic pan-hypopituitarism: Simmond’s cachexia
2. Mass effect:
 Chiasm: Bitemporal Hemianopia, decreased VA): Compression on the inferonasal fibers that
decussate at the anterior and inferior aspect of the chiasm leads to superior temporal
quadrantanopia, then bitemporal hemianopia.
 3rd vent (HCP),
 Cavernous Sinus (CNs III-V2-3, VI palsy), Diplopia, proptosis, facial pain, Miosis.
 CSF rhinorrhea (Invasive)
 Hypothalamic involvement may produce: hypotension, thermal dysautoregulation, cardiac
dysrhythmias, Respiratory pattern disturbances, Diabetes insipidus, altered mental status: lethargy,
stupor or coma
3. Headache (raised intra sellar Pressure: diaphragm stretch, Hypothalmic encroachment (cluster) and
ICP)
CLINICAL PRESENTATION

10. MODIFIED HARDY’S CLASSIFICATION
EXTENSION
SYMMETRICAL
Grade A: Suprasellar cistern only;
Grade B: Recess of the third ventricle
Grade C: Whole anterior third ventricle
ASYMMETRICAL
Grade D: Intracranial extradural
Grade E: Extracranial extradural -Beneath
cavernous sinus
INVASION / SPREAD
Floor of sella intact
I: Sella normal or focally expanded; tumor ≤ 10mm
II: Sella enlarged; tumor ≥ 10mm
SPHENOID EXTENSION
III: Localized perforation of sellar floor:
IV :Diffuse destruction of sellar floor:
DISTANT SPREAD
V: Spread via CSF or blood-borne
Anterior recess Displaced 3rd ventSuprasellar expansion Intradural extension
Beneath cavernous
(extradural
extension)

11.  A coronal view of cavernous sinus and adjacent structures. Three
lines pass through supra and intracavernous parts of internal carotid
artery (ICA):
 Medial line : connects the medial wall of ICAs
 Median line : crosses across the centers of ICAs
 Lateral line : touches the lateral wall of ICAs
 Grade 0 : Adenoma does not extend the medial carotid line
 Grade 1 : Adenoma crosses the medial line, but doesn't extend past
the median line, or so-called "intercarotid" line
 Grade 2 : Tumor extends beyond the median line, but doesn't
extend beyond the lateral line
 Grade 3 :Tumor extends beyond the lateral line
 Grade 4 : Tumor totally wraps around the intracavernous carotid
artery
CAVERNOUS INVOLVEMENT BY
PITUITARY MACROADENOMA
Micko et al (2015).
Subdivided grade 3 into:
3A - the tumor extends to the lateral line superiorly (over ICA)
3B - the tumor extends to the lateral line inferiorly (under ICA)
KNOSP CLASS

12. KNOSP’S CLASS OF CAVERNOUS
INVASION

13.  Microadenoma: <1cm diameter.
 50% of pituitary tumors are <5mm at time of diagnosis.
 These may be difficult to find at the time of surgery.
 Macroadenomas: Tumors >1 cm diameter
 Giant adenoma: >4cm: Usually invasive.
CLASSIFICATION: SIZE

14. HORMONE SECRETION AND FEEDBACK LOOP
The level of end product maintains the negative feedback, except for
the somatotrophs, where GHRH promotes GH release while
somatostatin inhibits.

15.  Adenoma of Lactotroph cells.
 Prolactin: Normal: Male: 2-18ng/ml, Female: 2-29 (pregnant (10-1=210ng/ml).
 Presentation: 50% of primary amenorrhoea, Amenorrhoea-galactorrhoea syndrome
(Forbes-Albright).
 Prolactinoma: PRL> 200ng/ml
 Prolactinemia <200mg/ml: Physiological: stress, exercise, pregnancy, lactation, Stalk
effect,infiltrating hypothalamic lesion, Drugs (Metoclopromide, estrogen, TCA,
Ranitidine), Empty sella, post ictal, CRF, Cirrhosis.
 Prl >1000ng/ml (false low in giants adenoma due to hook effect on Radioimmunoassay).
 If >500ng/ml: surgery may address hyperprolactinoma, RCC, HCC, lymphoma,
 Algorithm: >500ng/ml start medical treatment then surgery once Prl is <500.
Prolactin treatment for >1 year will render only 50% success rate of surgery due to
fibrosis.
PROLACTINOMA

16.  Extremely high PRL levels may overwhelm the assay (the large numbers of PRL
molecules prevent the formation of the necessary PRL-antibody-signal complexes for
radioimmunoassay) and produce falsely low results.
 Have the lab perform several dilutions of the serum sample and re-run the PRL, especially
in patients with clinical hyperprolactinemia
 Macroprolactinemia
 A situation where prolactin molecules polymerize and bind to immunoglobulins.
 Prolactin in this form has reduced biologically activity but produces a laboratory finding
of hyperprolactinemia.
HOOK EFFECT
It will saturate the antibodies and
fail to form the antibody sandwich
complexes that are required for
most radioimmunoassay.
Excess hormone will be washed
away with the labeled antibody, and
the test result will be falsely low.
These samples should be diluted to
provide a more accurate PRL level.

17.  Cushing diseases: Hypersecretion of ACTH. 50% have <5mm tumor. Lab: High serum
cortisol and urinary cortisol or 17 hydroxycorticosteroid, Normal or elevated ACTH,
Hypokalemic alkalosis, loss of diurnal variation, failure to suppression on low (1mg) dose
dexamethasone, Low CRH.
 Acromegaly: Bony hypertrophy, Colonic polyposis, Cardiomegaly, DM, Multiple cranial
nerve palsy, Carpel TS, GH, IGF-I.
 Medication: Octreotide, Pegvosement, bromocriptine, cabergoline, Pergolide.
CUSHING’S DISEASE

18.  Patients with a pituitary mass should undergo a complete neurologic and endocrinologic evaluation including a detailed history
and physical examination to assess for signs or symptoms of hyper-secretory syndromes such as Cushing disease, hyper-
prolactinemia, or acromegaly.
 Endocrinological testing is needed to determine hormonal function.
 Prolactin, FSH, LH, GH, insulin-like growth factor 1 (IGF-1), ACTH, cortisol, TSH, thyroxine, estradiol, and testosterone.
 Plain radiographs (cone down lateral view x ray): enlarged, round sella. and the sellar floor anatomy, pneumatisation of air sinus.
 High-resolution magnetic resonance imaging (MRI) with cuts through the sellar region is essential for surgical planning, as it will
show the precise size and location of the lesion as well as its relationship with the chiasm, cavernous sinus, and other surrounding
structures.
 75% are low signal on T1WI, and high signal on T2WI (but 25%can behave in any way, including completely opposite to
above). Enhancement is very time-dependent.
 if you are hunting for a microadenoma, then a dynamic MRI increases the chances that you might catch the tumor at a time when it
enhances differentially from the gland.
 Imaging must be done with 5 minutes of contrast administration to see a discrete microadenoma.
 Initially, gadolinium enhances the normal pituitary (no blood brain barrier) but not the pituitary tumor. After ≈ 30 minutes, the
tumor enhances about the same
 Dynamic MRI scans have been used to increase the sensitivity (contrast is injected while the MRI scanner is running).
 CT SCAN:
 Direct coronal or coronoal reconstruction thin cut axial computed tomography (CT): sphenoid sinus anatomy: Types: Sellar,
Presellar, post sellar and conchal type (less pneumatised).
 Cerebral angiography to demonstrate parasellar carotid arteries and to R/O aneurysm as a possibility (if MRA not
done/contraindicated); also assesses the ICA encasement.
 Calcium in pituitary usually signifies hemorrhage or infarction within tumor.
 Ophthalmological evaluation and Visual field charting (Perimetry)
 Nasal swab as a pre-operative antiseptic workup.
WORK-UP

19. WORK UPA CASE OF ACROMEGALY
SINGLE RANDOM BASAL GROWTH HORMONE LEVEL
<5ng/ml >10ng/ml
Normal Acromegaly
Single random basal may not be reliable; pulsatile secretion pattern
Sporadic peak >50ng/ml and as low as 37pg/ml: cant be used as diagnostic tool
Oral Glucose suppression test measurement at 0,30,60,90,120 min after 75mg oral
glucose load
GH nadir: <1ng/ml GH nadir: >1ng/ml
Also high in
Liver diseases
uncontrolled
DM
CRF
Pituitary tumor:
GHRH (+) RESPONSE
Ectopic GH secreting tumor
GHRH (-) RESPONSE
IMAGING
Acromegaly proven
SPECT: Octreotide scan with 6.5mCi of Indium111 :
scan after 4 & 24 hr: Hot spots
1. IGF-1 (Somatomedin-C) level: RECOMMENDED
Excellent integrative marker of average GH secretion:
Extremely sensitive for acromegaly.
1. Growth-hormone releasing hormone (GHRH) levels:
Differentiate: pituitary cause V/S ectopic acromegaly .
Oral glucose suppression test (OGST):
less precise and more expensive than
measuring IGF-1: useful than IGF-1 for
monitoring initial response to therapy.
Ruled out
Stringent criteria for a cure or remission of acromegaly
require:
• Random GH less than 2.5 ng/ml, or
• GH nadir after an oral glucose tolerance test of less than
1 ng/ml and
• A normal age and gender- normalized IGF-1, with no
clinical symptoms.

20. Primary work up to rule out Small cell lung ca,
Pancreatic ca, pheochromocytoma, Medullary
thyroid ca and thymoma.
WORK UPA CASE OF CUSHING SYNDROME
Not suppressed
Suppressed in normal individuals
24hr urine 17-OHCS: <4mg/24hr
Low dose (1mg) Dexamethasone suppression test or 2 day low dose test (0.5mg q 6hr
ACTH independent ACTH Dependent
High dose 8mg
CRH or AVP
Metyrapone
Not
suppressed
ACTH
unchanged
ACTH
unchanged
Suppressed
ACTH
increased
ACTH
increasesd
Serum Cortisol: <140 nmol/L
Urinary free cortisol: <50 nmol/L
Urinary 17-hydroxy cortiosteroid: <6.9 nmol/L
1. Assess the cortisol production in 24 hours in serum and
urine ( Normal 24hr serum cortisol: 20-90ug/ml, Urinary
17-OHCS: >150ug/ml), cortisol < 1.8ug/dl: cushing is
ruled out. Cortisol> 10 ug/dl: CS is probably present.
2. Assess sensitivity of HPA axis to negative feedback by
glucocorticoids.
3. Assess ACTH dependency:
• ACTH dependency diseases: Excess ACTH >>> Excess cortisol;
• ACTH independent diseases: Excess cortisol, Low ACTH, HPA
suppressed.
4. CRH and AVP are secretagogue and causes increased
secretion of ACTH.
5. Metyrapone are cortisol synthesis inhibitors: Increased cortisol or urinary 17-OHCS.
6. If imaging is not conclusive of microadenoma: then adopt Inferior petrosal sinus sampling/ Cavernous venous sampling (more accurate but highly morbid
than IPSS).
Bilateral femoral catheter B/L IJV IPS; Simultaneous ACTH measurement after CRH stimulation.
IPS: Peripheral ACTH: 2:1 (95% S; 100% S); 3:1: ( both 100%), Inter sinus gradient (>1.4) lateralize the lesion in 75%cases. Measure prolactin level too

21. 1. Rathke cleft cyst may appear similar to a cystic pituitary adenoma.
2. Tuberculum sellae meningioma may compress the chiasm: No enlargement of the sella.
3. Craniopharyngioma is more often a suprasellar lesion.
4. Metastasis to the sella: diabetes insipidus or extraocular muscle palsies
5. Internal carotid artery aneurysm may fill the sella: a flow void T2W MRI.
6. Sarcoid granuloma or tuberculoma: rare.
Differentials

22.  Medical
 Surgical
 Radiotherapy
TREATMENT

23. Medical management

24.  Dopamine agonists (DA) unless there is unstable deficit.
 Debulk the tumor transsphenoidally and then rechallenge with DA therapy.
 For unstable deficit
 Non-responders
PROLACTINOMAS
Drug Dose Complication Remarks
Bromocriptine
semi-synthetic
ergot alkaloid
D1 & D2 agonist
1.25mg (PO/Vaginal)
Adjust: 2-4wks for micro; 3-4 days for
macroadenoma
Check initial PRl level at 4 weeks.
To shrink tumor: 7.5mg in 3 div dose x
6 months
Reduces PRl level to <10% of pre-
treatment values in most patients.
Reduces size in 6-8wks in 75% patients
GI symptoms, orthostatic
hypotension,
vasodilation,nasal
congestion, psychiatry
(depression), nightmare
Shrinks and increases risk of
CSF leak.
Prolonged treatment with
bromocriptine may reduce
the chances of surgical cure
by 50% if >1yr
Pregnancy: 3.3%:congenital
anomalies
11%: Spontaneous abortion
rate = Normal population
Cabergoline
ergot alkaline
derivative D2
agonist
0.25 mg PO twice weekly; increase by
0.25mg q 4 weeks (max 3mg/week);
T1/2 60-100hrs
Check initial PRl at 4 weeks
Less than bromocriptine,
can be given in pregnancy,
Cardiovascular complication
in high dose (10X dose in
parkinsonism): Valvular
heart diseases-
Regurgitation due to valve
fibrosis.( activates 5-HT2 B
receptors which induces
prolonged mitogenic effects
in fibromyoblasts, which
may lead to valvular
fibroplasia
Control of PRLand
resumption of ovulatory
cycles may be better than
with bromocriptine.
Contraindicated in
eclampsia or pre-eclampsia,
uncontrolled HTN

25.  Long-term therapy with DA agonists has some cytocidal effect on pituitary tissue.
 24 months therapy was associated with >95% recurrence rate
 Recent literature suggests a 20–30%chance of normoprolactinemia off medication in
select patients.
 When to stop: Recommendations:
 If response to DA agonist is satisfactory, treat for 1–4 years (microadenomas: check
prolactin yearly, macroadenomas are more likely to grow and should be checked more
often).
 Microadenomas or macroadenomas that are no longer visible on MRI are candidates
for DA agonist withdrawal.
 For microadenomas: discontinue the drug;
 For macroadenomas: slowly taper the drug then discontinue.
 Recurrence rate is highest during 1st year, check prolactin levels and clinical symptoms
every 3 months during the 1st year. (0,3,6,9,12months).
 Long-term follow up is required, especially for macroadenomas.
DISCONTINUING MEDICATIONS

26.  Agents have been used pre-op in some cases to try to decrease tumor size for surgery.
 Bromocriptine: Size reduction in only ≈ 20% of patients.
 Octreotide reduces tumor volume in ≈ 10% of cases.
 Paucity of dopaminergic receptors on cell membranes in these tumors.
 Surgery and/or XRT are usually the initial treatment of choice for hormonally inactive
tumor.
 Follow-up recommendations for medically managed hormonally inactive macroadenomas
 For asymptomatic microadenomas (<1 cm dia), recommend: F/U pituitary MRI at
years 1, 2, 5 and ± 10 (can stop F/U after 10 and possibly 5 years if no growth).
 For tumors >1 cm, recommend: check visual fields, pituitary bloodwork (to R/O
pituitary insu ciency) and pituitary MRI at years 0.5,1,2 &5, and any time symptoms
develop.
NON RESPONDERS

27. PROLACTIN LEVEL WITH DAAGONIST TREATMENT
PRL LEVEL (NG/ML)
RECOMMENDATION
<20
Maintain
20–50
Reassess dose
>50
Consider surgery

28.  Asymptomatic: Do no harm: Observe
 An aggressive surgical approach is indicated with these tumors since the secretion product is harmful
and effective medical adjuvants are lacking.
 Pre-treat invasive GH-secreting tumors with somatostatin analogue therapy before surgery to reduce
surgical risks (general and cardiac).
 Elderly patients or tumors >4 cm diameter:
 Debulk tumor transsphenoidally and/or adjuvant therapy (XRT and/or medications)
 Young age and size <4 cm:
 Radical surgery (may utilize a cranio-orbito-zygomatic skull base approach; may be curative)
 Medical therapy:
 Patients not cured by surgery
 Cannot tolerate surgery (e.g. due to cardiomyopathy, severe hypertension, airway obstruction
 For recurrence after surgery or XRT
 XRT
 For failure of medical therapy.
 To buy time among surgical failure who are awaiting XRT
 GH levels decline very slowly after XRT.
GH secreting tumor

30.  Elderly patient: expectant management is an option, with intervention for signs of
progression (radiographic or neurologic).
 Parasellar tumor and/or young age: Radical surgery (often not curative)
 Central tumor or elderly patient with progression: trans-sphenoidal tumor debulking
and/or XRT and close follow up.
 Radiation therapy:
 Recurrent or residual tumor or in patients who cannot tolerate surgery.
 1.6 to 2 Gy four or five times per week for 5 to 6 weeks, for a maximum dose of 45 to
50 Gy.
 Radiotherapy controls tumor growth in 80% to 98% of non- functioning tumors
 May be considered: Dopamine agonists, valproic acid, somatostatin analogues,
rosiglitazone, and serotonin agonists.
Non-functional adenomas

31. 1. SRS is generally able to use a higher radiation dose per fraction than is conventional radiation, and it
usually results in earlier endocrine control and induction of remission.
2. Stereotactic radiosurgery uses only a single session deliver focused radiation to lesion with less
radiation to surrounding structures.
3. Options of SRS: GKS, LINAC, Cyberknife, FSRT, Proton beam therapy.
4. The major concern from SRS is radiation damage to the visual pathways.
5. Reduced by limiting the radiation dose to the optic chiasm to less than 10 Gy
6. Not good candidates for SRS (may undergo FRST)
a. Adenomas closer than 2 to 5 mm to the optic chiasm or or conventional radiation
b. Larger than 30 mm in diameter.
7. Side effects:
a. Hormone deficiencie:13% to 41
b. Neuropsychiatric changes : SRS << conventional radiotherapy.
c. Radiation necrosis ~ 0.2%.
d. Optic neuropathy occurs in 1.7%,
e. Vascular changes in 6.3%,
f. Neuropsychological changes in 0.7%, and
g. Radiation-induced secondary malignancies in 0.8%.
SRS in PT

32. Hypo secretion Assessment Therapy
Corticosteroid Co-syntropin test to assess cortisol reserve
Failure to achieve a peak cortisol level>18 mcg/dl
Cortisol 20mg AM, 10mg PM
Hypothyroid Should never be started before corticosteroid risk
Adrenal crisis.
Synthyroid 125mcg/d
3-4 weeks for euthyroid
Testosterone Increase intratumor estradio and promote risk of
tumor growth
Only after stabilization of
tumor
HORMONE REPLACEMENT THERAPY
Dys thyroidism T4 TSH TSH response to TRH
Primary hypo Low or N Elevated Elevated
Secondary Hypo Low Low or N Reduced
Primary Hyper Elevated Subnormal NA
Secondary Hyper Elevated Elevated or
inappropriately normal
NA

33.  Rare (< 140 reports).
 Usually invasive and secretory (most common hormones: ACTH, PRL).
 Can metastasize, at which point prognosis is poor (66% 1-year mortality).
 Little improvement with further surgery, XRT, or chemotherapy.
PITUITARY CARCINOMA

34. GOALS OF SURGERY
 Eliminate mass effect from the pituitary and surrounding structures
 To preserve or restore pituitary and visual function
 To resect enough of the lesion to prevent recurrence, and
 To obtain tissue for histopathology analysis.
 OPTIONS:
 Craniotomy:Pterional/ Cranioorbitozygomatic approach.
 Trans sphenoid:
 Sublabial/Transnasal microsurgical
 Transnasal endoscopic
SURGERY

35. Thank you

NATIONAL INSTITUTE OF NEUROLOGICAL AND ALLIED SCIENCES, BANSBARI, KATHMANDUUPENDRA DEVKOTA MEMORIAL NATIONAL INSTITUTE OF NEUROLOGICALAND ALLIED SCIENCES,
BANSBARI, KATHMANDU