Pituitary adenomas: Clinical, neuro-ophthalmic, radiological evaluation and medical management

PITUITARY ADENOMAS
Presenter: Dr Kaushal Deep Singh
Moderator: Dr Abrar Ahad Wani
Sher-i-Kashmir Institute of Medical Sciences
(SKIMS), Soura, Srinagar
Date: 08/05/2019

Headings
Anatomical Overview
Functional Overview
Epidemiology
Clinical Presentation
Classification Systems
Specific Subtypes and their Hormonal and Medical
Management
Neuro-ophthalmic Evaluation
Radiological Evaluation
Investigation Protocols
Surgical Management Overview

Did you know??
• Robert Wadlow was
the tallest recorded
man on earth at a
height of 8 ft 11 in.
• His astounding
height was the
result of a pituitary
tumor.

Anatomical and
Functional Overview

PITUITARY GLAND – AN
OVERVIEW
 Weighs just 600 mg
 Cranio-caudal dimensions 8-10mm
 Exercises direct or indirect control on every organ
system
 Sella turcica - part of body of sphenoid bone
 Depth- upper limit 13mm
 Length - upper limit 17mm
 Width - upper limit 15 mm
 Volume - 1100 mm3

Adenohypophysis
 Secretes GH, PRL, FSH, LH, TSH, ACTH, MSH,
Endorphins.
 Adenohypophysis : divided into Pars tuberalis, Pars
intermedia, Pars distalis
 Delicate acinar architecture
 In horizontal cross section, composed of two lateral
wings and trapezoid central mucoid wedge
OVERVIEW

Somatotrophs Anterior part of the lateral wings
Lactotrophs Posterior part of the lateral wings
Corticotrophs Central wedge , just anterior to
posterior lobe
Thyrotrophs Anteromedial part of central
wedge
Gonadotrophs Through out pars distalis
OVERVIEW

Neurohypophysis
• Contains only axons and fenestrated
capillaries
• Divided into
 median eminence
 infundibular stem
 neural lobe
OVERVIEW

Cell type hormone Clinical syndrome Tumor type
Somatotroph Growth
Hormone
Acromeg/gigan Sparsely granulated GH cell
Densely granulated GH cell
Lactotroph Prolactin Amen/galactor Sparsely granulated prl
Densely granulated prl
Somato/Lact Gh+prl Acro+hyperprl Mixed GH-prl
Acro+hyperprl Mammo+somato
Amen/Gal/Acro Acido+stem cell
Corticotroph Acth/Pomc
/B-lph/Msh
Cushings, nelson Densely granulated acth
Sparsely granulated acth
Gonadotroph FSH,LH,A-
Sub Unit
Hypopituitarism Gonadotroph
Thyrotroph TSH, A-sub
Unit
Hyperthyroid/
Hypopituitarism
Thyrotroph
NULL Cell None Hypopituitarism Null cell
oncocytoma

PITUITARY TUMOURS
10-15% of all primary
brain tumours; Present
as incidental finding in
5-20%
Annual incidence of 8.2
– 14.7 case / 100000
population
Though incidence is
equal, it is diagnosed
more commonly in
females

Third most
common primary
brain tumours
Autopsy
incidence: 20-
25% of
population
10% of routine
MRI scans show
occult pituitary
microadenoma
Between 3rd – 6th
decade of life

PITUITARY TUMOURS
Genetics
MEN 1
3% of all pituitary tumours
Autosomal dominant disorder
Variable penetrance
Occurs in 25% of affected patients with MEN 1
PRL or GH macroadenomas

PITUITARY TUMOURS
ADENOHYPOPHYSIS
Pituitary adenomas
NEUROHYPOPHYSIS
Metastatic tumours
Primary : rare - gliomas, granular cell
tumours,hemartomas

PITUITARY ADENOMAS
Functioning
Young adults
Non functioning
With increasing
age

Adenoma type Prevalence %
Prolactin cell adenoma 30
GH cell adenoma 15
ACTH cell adenoma 10
Gonadotroph adenoma 10
GH/PRL cell adenoma 7
TSH cell adenoma 1
Nonfunctioning adenoma 25

PITUITARY ADENOMAS
Gross :
 Yellowish grey to purple, soft fluid to creamy
texture
Histological:
 Cellular monomorphism
 Lack of acinar organization
 Uniform cytoplasmic staining, pleomorphic
cells , prominent nucleoli, mitotic figures.

Clinical Presentation
Presentation
Hypersecretion
Pituitary
insufficiency
Mass
effect
Incidental
finding
Apoplexy

Hypersecretion
70% of pituitary adenomas
are endocrinologically active
Most common mode of
presentation
Presentation varies according
to the hormone in excess

Pituitary Insufficiency
By compression of
non-tumourous
pituitary, pituitary
stalk, hypothalamus
Chronic process,
can be acute as in
pituitary apoplexy
Gonadotrophs most
vulnerable

Mass effect
HEADACHE VISUAL LOSS
HYDROCEPHALUS
INTRACAVERNOUS
EXTENSION

Non-functioning Adenomas
25-30 % of patients do not have classical
hypersecretory syndromes
May grow to a large size before they are
detected
Present due to mass effect
 Visual deficits
 HA
 Hormone deficiency

• Acute presentation secondary to tumor
hemorrhagic necrosis/infarction
• Headache
• Vomiting
• Blindness
• Ocular paresis
• Altered level of consciousness
• Occur in pregnancy
• Compresses hypophysial portal vessels
• Treatment : high dose steroid / early surgery
Apoplexy

Clinical Manifestations
Hormonal deficiencies - Clinical effects
Growth hormone
deficiency
• Adults - Increased rate
of cardiovascular
disease, obesity,
reduced muscle strength
and exercise capacity,
and increased
cholesterol
• Infants –Hypoglycemia
• Children - Decreased
height and growth rate
Gonadotrophin deficiency
• Men - Diminished libido and
impotence; testes shrink in
size, but spermatogenesis
generally preserved
• Women - Diminished libido
and dyspareunia; breast
atrophy in chronic deficiency
• Children - Delayed or frank
absence of puberty
Thyrotropi
n
deficiency
• Malaise,
• weight gain,
• lack of energy,
• cold intolerance,
• constipation

Hormonal deficiencies - Clinical effects
Corticotrophin deficiency
• Initially, symptoms nonspecific (eg, weight
loss, lack of energy, malaise); severe adrenal
insufficiency may present as a medical
emergency
Panhypopituitarism
Refers to
deficiency of
several anterior
pituitary
hormones.

Hormonal overproduction - Clinical effects
Prolactin *
• Hypogonadism, if
hyperprolactinemia
sustained
• Women -
Amenorrhea,
galactorrhea, and
infertility
• Men - Decreased
libido, impotence,
and rarely
galactorrhea
Growth hormone
• Children and adolescents - May result
in pituitary gigantism
• Adults – Acromegaly Changes in the size
of the hand and feet, coarseness of the
face, frontal bossing, and prognathism
result. Further changes in the voice, and
hirsutism, confirm the diagnosis.
• Acromegaly frequently results in
glucose intolerance, with 20% of
patients progressing to diabetes
mellitus.
• Carpal tunnel syndrome is seen
frequently.
Cushing
disease
• Weight gain,
central
obesity,
moon facies,
violet striae,
easy
bruisability.

HARDY’S Classification
Microadenomas – Grades 0 and I
Macroadenomas – Grades II to IV
Grade 0 : Intrapituitary microadenoma with
normal sellar floor, size < 10 mm
Grade I : Normal-sized sella with asymmetric floor, size <
10 mm
Grade II : Enlarged sella with an intact floor, size > 10
mm
Grade III : Localized erosion of sellar floor, size > 10 mm
Grade IV : Diffuse destruction of floor, size > 10 mm

Modified Hardy Wilson Classification
Type A: Tumor bulges into the
chiasmatic cistern
Type B: Tumor reaches the
floor of the 3rd ventricle
Type C: Tumor is more
voluminous with extension
into the 3rd ventricle up to the
foramen of Monro
Type D: Tumor extends into
temporal or frontal fossa
TYPE E : Extradural spread
(extension into or out of the
cavenous sinus)

Pathologic Classification
Chromophobic –
Non-functioning
Basophilic –
Cushing’s
Acidophilic -
Acromegaly
Mixed

WHO Classification
Five-tiered
system
• Clinical presentation and
secretory activity
• Size and invasiveness (e.g.
Hardy)
• Histology (typical vs. atypical)
• Immunohistologic profile
• Ultrasturctural subtype

Microadenoma < 10 mm diameter Secreting adenoma
Macroadenoma > 10 mm diameter Mass effects
Non secreting
Classifying Adenomas by Size

Classification Of Pituitary Adenomas According
To Endocrine Function
Pituitary adenomas are classified by their cell of
origin
Lactotroph adenoma
Gonadotroph adenomas
Somatotroph adenomas
Corticotroph adenomas
Thyrotroph adenomas

Classification Of Pituitary Adenomas According
To Cells of Origin
Adenomas With
 GH excess
 PRL excess
 ACTH excess
 TSH excess
 FSH / LH excess
 PLEURI hormonal adenomas
Adenomas With No Apparent Hormonal Function

Discussion of Specific
Sub-types of Pituitary
Adenomas

Prolactin
< 25 ng/ ml : normal
25-150 ng/ml:
 prolactinoma
 stalk effect
 drugs
 Hypothyroid
> 150 ng/ml : prolactinoma
Hook effect
even large elevations will show normal PRL levels on
testing due to large size of molecules. Do serial
dilutions

A. Prolactinomas
Most common primary tumour of pituitary
30% of all pituitary adenoma
Female:male = 20:1 for microadenoma
1:1 for macroadenoma
Characterized by hyperprolactinemia
Majority are microadenomas; 30% in females are self-limiting
Prolactin
< 25 ng/ ml - normal
25- 150 ng/ml - prolactinoma(±), stalk effect, drugs,
hypothyroidism
> 150 ng/ml - prolactinoma (pure or mixed)
> 1000 ng/ml - invasive prolactinomas

Prolactinomas
CLINICAL PRESENTATION
Hypogonadism
Menstrual irregularities like secondary amenorrhea, delayed
menarche, oligomenorrhea , infertility.
Galactorrhea (in 80% females and 30% males)
Decreased libido
Headcache
Visual disturbances
Hypopituitarism
Psychological

Prolactin Function
Serum prolactin levels ( normal 5-20ng / ml)
Dynamic tests:
 not used if prolactin levels > 150ng / ml or tumor is found on
MRI / CT
 used if prolactin levels are mildly elevated and MRI findings are
equivocal
 Stimulation tests :
 TRH
 Chlorpromazine
 Metoclopramide
 Suppression tests:
 L-dopa
 Nomifensine

Prolactinomas
Only pituitary tumor for which medical
therapy has a proven primary role
Observation
Dopamine agonist
 Bromocriptine
 Cabergoline

Dopamine agonist
Selective activation of D2 receptors located on
lactotroph cell surface
↓
Decrease adenylate cyclase activity
↓
Decrease in C- AMP level
↓
Inhibition of PRL synthesis and release.

Dopamine agonists:
Bromocriptine
Cabergoline
Pergolide mesylate
Lisuride
Quinagolide
Side effects– GI intolerance, postural hypotension,
constipation, nasal stuffiness

Prolactinomas
Indications for dopamine agonist therapy:
Non invasive prolactinoma and serum prolactin
level 150-500ng/ml
Serum prolactin level >1000ng/ml
Residual / recurrent prolactinoma following
surgery

Bromocriptine:
2-bromo-α-ergocryptine mesylate
Developed by Flückiger and colleagues in the
late 1960s
Purpose was inhibiting prolactin secretion
without the uterotonic, vasospastic properties of
other ergots

Serum levels peak after 3 h, and the nadir is observed at
7 h with very little bromocriptine detectable in the
circulation after 11-14 h.
Absorption rate from the GI tract is 25-30%.
Very high first-pass effect, with 93.6% of a dose being
metabolized and only 6.5% of an absorbed dose
reaching the systemic circulation unchanged
Excreted via the biliary route into the feces
Levels in the fetus about one-fourth of that found in
maternal blood
Start low dose at 1.25 - 2.5 mg day at night before
increasing to 2.5 – 10 mg per day in divided doses
Take with food to reduce side effects

Cabergoline:
 more effective
 less side effects than Bromocriptine
 more expensive
 given once or twice a week with a starting dose of
0.25 mg 2 x week
Titrate these based on prolactin levels and tolerability

Criteria for cure:
Normal prolactin level
Asymptomatic
Negative MRI study for 5 years
If prolactin level is <100ng/ml and shows no
tendency to rise is indicative of stalk damage

B. Growth Hormone Secreting
Pituitary Adenomas
Growth hormone
• Most abundant pituitary hormone
• Secretion is pulsatile
• Physiological excess seen in stress, trauma,
sepsis, estrogen replacement
• Exerts it’s action through IGF -1

Growth Hormone Secreting Pituitary
Adenomas
 Equal incidence in males and females
 More than 60% are macroadenomas
 4th and 5th decade
 15-20% of all pituitary tumors
 Pre-op duration 10 years to diagnosis in adults and 3.1 years in
children
 Pleurihormonal
 Overall mortality is increased 3 folds as compared to age matched
controls

Growth Hormone Secreting Pituitary
Adenomas
GH excess
Before epiphyseal closure - gigantism
Beyond puberty - acromegaly

Diverse Manisfestations
1. BONE AND
SOFT TISSUE-
coarse facial
features
frontal bossing,
prognathism,
maxillary
widening,
dental
malocclusion
Snoring sleep
apnea, low voice
Macroglossia
Spade like
enlargement of
hand and feet
Malodorous/oily
perspiration
2. CARDIOVASCULAR
HYPERTENSION
CARDIOMYOPATHY
ARRHYTHMIAS
3.Musculoskeletal
Arthropathies
Kyphosis
Spinal stenosis
Barrel chest
Osteoarthritis
4. Increased incidence of premalignant
polyps/ colonic cancers
5.Diabetes mellitus

Acromegaly work-up
Chest and abdomen imaging for ectopic GHRH
secreting tumors
Empty sella shows pituitary infarction
Scintigraphy
Ancillary tests
Blood glucose, urine, cardiac and respiratory
screening for colorectal neoplasia

Diagnosis
Random GH – not useful gives false positive and false
negative results
Insulin like growth factor 1 (IGF-1) – best
for screening (represents average daily GH secretion)
Insufficient GH suppression on oral
glucose tolerance testing – gold standard to
confirm diagnosis : 75 mg of glucose load normally suppresses
GH< 2ng/ml RIA. GH nadir >2ng/ml RIA with adenoma confirms it

Somatomedin-C (IGF-1) : always elevated in acromegaly
GH levels: fasting state and after administration of
stimulatory or inhibitory agents
 Stimulatory tests :
 Insulin induced hypoglycemia after IV administration of 0.1-
0.15 IU/Kg of plain insulin
 GH level >5ng / ml indicates normal function
 it is avoided in elderly, those with cerebro vascular disorders
or convulsive disorder
 Oral glucose suppression test: Failure of suppression of
elevated levels of GH to < 2ng / ml after 75 gm glucose
loading
Acromegaly

Clinically Acromegaly, MRI pit adenoma, GH>5ng/ml
If GH<5ng/ml
IGF-1, elevated
If no
Oral glucose suppression test confirms it
rarely MRI negative ,
measure GHRH levels, CECT abd /chest

Acromegaly
Indications of medical management:
 Failure of surgery to normalize IGF 1 levels
 Awaiting the beneficial effects of RT
 Unresectable tumors

Drugs :
Somatostatin analogues
Dopamine agonists
GH receptor antagonist - Pegvisomant

Limitations :
Cost
Inability of tumor shrinkage sufficient to
relieve any mass effect

Somatostatin analogues:
Octreotide :45 times more potent.
 half-life in plasma being 113 min
 peak plasma concentrations within 1 h
 suppress GH levels for 6–12 h
 Mechanism of action
 Inhibit GH secretion
 partially inhibits GH-induced IGF-1 generation
 simulates IGF-BP1 expression
 reduce GHRH release

 Clinical improvement-
headache 84%
hyperhydrosis 65%
decrease in ring size in 55%
improvement in cardiac function and sleep
apnea

Octreotide
(S/C) 100 to
500 mic.gm
TDS
Octreotide
LAR
(I/M) at 28
days interval
Lanreotide
(I/M) every 7-
14 days
Pegvisomant
GH
REDUCTION
47% 56% 50% Not useful
IGF1
REDUCTION
46% 66% 48% 97%

Dopamine agonists :
Used both as primary and adjuvant
treatment
 Bromocriptine up to 20 mg/day
 Cabergoline 1–2 mg/week
Response rate low

Bromocriptine Cabergoline
GH REDUCTION 20% 44%
IGF1
REDUCTION
10% 35%
Dopamine agonists :

GH-Receptor Antagonist :
Pegvisomant :
Check IGF 1 level every 4-6 weeks
Monitoring GH not useful
Dose 10-40 mg/d

C. ACTH Secreting Pituitary
Adenomas (Cushing’s Disease)
• 5 to 10 times more common in females than
males
• 3rd and 4th decade
• 10-15% of all pituitary tumors
• 90% microadenomas
• 55 % pit adenoma in children
• Highest morbidity of all pituitary hypersecretory
disorders
• Most common cause of death is cardiovascular
complication

Cushing’s Disease
Chronic Exposure of Tissues to Excessive Cortisol
Moon facies
Centripetal obesity
Buffalo hump
Thin skin ,purple abdominal striae, ecchymosis
Psychological
Glucose intolerance
Hematopoietic features include leukocytosis, lymphopenia, eosinopenia
Osteoporosis, proximal myopathy,
Impaired immune function
Hirsutism, acne menstrual irregularities in females
Oligospermia, impotence in males

Cushing’s Syndrome vs. Cushing’s
Disease
Cushing’s syndrome is a syndrome due to
excess cortisol from pituitary, adrenal or other
sources (exogenous glucocorticoids, ectopic
ACTH, etc.)
Cushing’s disease is hypercortisolism due to
excess pituitary secretion of ACTH (about 70%
of cases of endogenous Cushing’s syndrome)

Evaluation Of Suspected Cushing`s
Syndrome
HISTORY: increased weight, growth retardation
in children , weakness, easy bruising, stretch
marks, poor wound healing, fractures, change in
libido, impotence, irregular menses, mood
changes
EXAMINATION – fat distribution, hypertension,
proximal muscle weakness, thin skin and
ecchymoses, purple striae, hirsutism, acne, facial
plethora, edema.

Corticotroph adenomas
Laboratory Evaluation
1. Establishing hypercortisolism
2. Distinguishing ACTH- dependent from ACTH
independent causes of hypercortisolism
3. Differentiating Cushing’s disease from
ectopic states of ACTH excess

Establishing hypercortisolism
Urinary free cortisol
 Sensitivity 45–71%,100% specificity (best screening test)
Overnight dexamethasone suppression test or Low dose
dexamethasone suppression test (Liddle test)
 Sensitivity 95 % and specificity 88%
 1 mg of dexa at 11.00 am and measurement of serum cortisol
at 8.00 am
<5 mcg/dl- normal
5-10 mcg/dl equivocal
>10mcg diagnostic
Plasma corticotropin level->20pg/ml diagnostic
>10 pg/ml suggestive
<5pg/ml corticotroph independent

Nocturnal Salivary Cortisol:
93% sensitivity, 100% specificity.
Levels < 4.0 nmol/l, the diagnosis of
significant Cushing’s syndrome is unlikely
7–8 nmol/l are abnormal

Establishing ACTH Dependency
Measurement of plasma ACTH levels
ACTH level <1.1 pmol/L (5 pg/mL) by IRMA is
consistent with an ACTH-independence
Corticortroph adenoma: moderate elevation
Ectopic ACTH producing lesion: marked
elevation

Differentiating Cushing’s disease
from ectopic states of ACTH excess
High dose dexamethasone suppression test (if
corticotrops >10 pg/ml): 2 mg qid for 48 hrs and
measurement of urinary cortisol/17-
hydroxycorticosteroid; > 69% fall in 24 hr UFC (pre
and post dexa ) is 100% specific for CD
Overnight 8 mg dexamethasone test: 8 mg
dexamethasone is given at 11.00 pm and drop in
>50% S. cortisol at 8 AM indicates CD.
CRH stimulation test: 1 mcg/kg CRH IV in morning, if
increases >35% corticotropin level at 15, 30 min
above baseline yields 100% specificity and 93%
sensitivity for CD
Metyrapone Test (inhibitor of 11β-hydroxylase)

Inferior petrosal sinus
sampling
Classical clinical and biochemical CD features with
MRI negative patient equivocal suppression and
stimulation test
Diagnostic accuracy is 80-100%
Blood samples are obtained at basal and 3,5,10 min
after CRH administration and ips/ps ratio calculated
 ips/ps >3 CD
 ips/ps <2 ectopic
 rarely 2-3 ectopic
IPS gradient helps in lateralization of adenoma

Diagnosis
Cushing ‘ s
Syndrome
?Primary Cushing
syndrome(Cushing’s
disease)
??secondary
hypercortisolism
(ectopic Cushing's
syndrome)
???primary
hypercortisolism
(adrenal Cushing
syndrome)

Diagnosis
24 hr urinary free
cortisol(>100mcg) 1 and 17
OH-corticosteroids (>12mg)
1 mg overnight
dexamethasone test- best
screening test
Low dose dexamethasone
suppression test
High dose dexamethasone
suppression
Plasma ACTH levels
Inferior petrosal sinus
sampling

Cushings disease
Indications for medical management:
Failure of all other treatment modalities
Preparation for surgery to relieve extreme
symptoms
Interval between RT and development of
eucortisolemia

Drugs :
Ketoconazole
Aminoglutethimide
Metyrapone
Mitotane
Etomidate
Mifepristone
Octreotide

Ketoconazole: First line drug
 17α-hydroxylase,11β-hydroxylase,18-
hydroxylase, and especially 17,20-lyase
enzymes are all blocked by ketoconazole
 400–1200 mg/d (average 800 mg/d)
 Effective in 70-100%
 Liver toxicity 15%

Aminoglutethimide
 Inhibits the first step in cortisol biosynthesis
(cholesterol → pregnenolone)
 Effective 50%
 250-2000 mg/day
 Can be given with ketoconazole

Metyrapone
 Selective inhibitor of 11β-hydroxylase
 Effective in 85%
 Doses of 750-2000 mg/d
 Acne, hirsutism

Mitotane
 Adrenocorticolytic effects and direct inhibition of
steroid synthesis
 2-4 g/day
 Effective in 80%, long term remission in 30%
 Higher response rate with concomitant pituitary
irradiation
 Contraindicated in women planning for pregnancy
within 5 years
 Side effects : gastrointestinal, hypercholesterolemia,
adrenal insufficiency

Etomidate
 Life-threatening situations with severe
hypercortisolism
 Oral dosing is contraindicated
 Dose of 0.1 mg/kg/h
 Eucortisolism achieved within 11–48 h by
using a continuous infusion

Mifepristone
 Major vegetative depression, suicidal ideation
with hypercortisolism

Octreotide
Ectopic ACTH source

D. Thyrotroph adenoma
TSH secreting tumors
1-2% of pit adenomas
Mixed hormonal secretion- 30%
GH, PRL, Gonadotropins
90% macroadenomas
Mean duration of presentation 9 yrs
Clinical features of goitre, warm skin, heat
intolerance, cardiac arrhythmias and other
hyperthyroid features,

Thyrotropic Function
T3 , T4 , TSH levels, Free T4, T3 by direct method, a-
subunit, PRL, GH, SHB, Iodine scan/USG of thyroid
If TSH levels are normal in the presence of low T3 / T4
levels then TRH reserve is tested
200 micro grams of TRH is given IV – if TSH is elevated
to > 6-20 micro units / ml : normal
 absence of response :
 total hypophysectomy
 Decreased response:
 thyroid hormone therapy
 glucocorticoid therapy
 Hyperthyroidism
 renal failure
 depression

Clinical suspicion, MRI –pit adenoma, baseline TSH,
free T4/T3,a-sub unit,PRL,GH
TSH normal, a-sub unit/TSH ratio
<5.7 in normogonads,<29.1 in hypergonad,
TSH elevated<0.7 in normogonads,
<1.0 in hypergonads
MRI equivocal, TRH stimulation test

Thyrotropin secreting adenomas
treatment
Somatostatin analogues:>90% respond
Dopamine agonists: Bromocriptine - 20
% respond

E. Gonadotropinomas
7-15% of pituitary adenomas
40-50% macroadenomas secrete
gonadotropins
Clinical features of mass effect: visual
symptoms, hypogonadism, amennorrhea,
hypothyroid, hypocortisolism

Gonadotropinomas
Lab investigations
• basal hormonal levels
• TRH stimulated gonadotropins, and sub
units
normally causes absent FSH response and no more
than 33% increase in LH and b- LH
primary hypogonadism LH,FSH elevated and don’t
respond to TRH
gonadotropinomas have greater than 60% increase
in b-LH levels

E. Gondotroph Function
CRITERIA :
Absence of other hormonal abnormality
Elevated basal and stimulated response of
gonadotropins

E. Diabetes Insipidus
Polyuria secondary to water diuresis and polydipsia
Due to low levels of ADH
High output of dilute urine
Craving for water, especially ice cold water
Incidence
 9.2% in micro adenoma surgery
 37% in case of total hypophysectomy
Mostly due to extreme sensitivity of hypothalamic
neurohypophyseal unit to local alterations in blood flow,
edema and traction on pituitary stalk and is transient
Permanent disturbance of ADH secretion –direct damage to
neuro hypophyseal unit

Types of presentation
Transient polyuria starting 1‐3 days after surgery and
lasting for 1‐7 days ; local edema and traction on
pituitary stalk
Triphasic response
 polyuria beginning 1‐2 days after surgery lasting for 4‐5 days
 normalization of urine output / SIADH like water retention 4‐5
days
 return of polyuria
Transient polyuria begining immediate post-op
Permanent polyuria beginning immediate post-op and
continuing without any interphase

DIAGNOSIS:
Urine output >250ml/hr (>3ml/kg/hr in pediatric
patients )
Urinary S.G. < 1004
Urinary osmolality <200mosm/kg
Normal or above normal serum sodium level
Normal adrenal function

Depends on :
Patients clinical status
Urine volume
Concentration of serum electrolytes
Creatinine
If alert, with intact thirst, mild DI,
Patient can self regulate water intake
DDAVP – nasal spray 2.5micro gm BD
If thirst mechanism is impaired
‐meticulous I/o records
‐daily wt measurement
‐frequent electrolytes , urea , hematocrit
‐supplementation of free water
‐vasopressin analogues

If consciousness is impaired
 Hourly I/O, urinary specific gravity
 4 hourly electrolytes
 Parenteral fluids
 Titrated dosages of desmopressin‐2‐4
microgm IV/SC in 2 divided doses

Chronic DI
• Rare in c/o trans sphenoidal surgery
• Treatment of choice is DDAVP
• Other drugs :
 clofibrate 500mg 2‐4 times/d
 chlorpropamide –50‐500 mg/day
 carbamazepine 400‐600mg/day

SIADH
Less common
Causes :
 Pre-op medications
 Anaesthetic agents
 Surgical stress
 Surgical irritation of neurohypophyseal unit

DIAGNOSTIC CRITERIA
Hyponatremia
Inappropriately concentrated urine
No evidence of renal /adrenal dysfunction
Low serum osmolality
No hypothyroidism
No evidence of dehydration/overhydration (Water
load test)
Symptoms of hyponatremia

TREATMENT
ACUTE SIADH : fluid restriction 0.5‐1.5 litres/day
 If sodium levels<120meq/l –hypertonic
saline+furosemide diuresis
 Correction rate of 0.5meq/hr
CHRONIC SIADH :
 long term fluid restriction
 demeclocycline 150-300mg q 6hrs
 furosemide 40 mg OD
 lithium
 phenytoin

Investigation Protocol
History and physical examination
Neuro- ophthalmology:
Acuity, field, fundus and movements
Hormone levels – basal hormone and dynamic testing
Aim- hypersecretory state/insufficiency
Radiology (a) X-Rays
(b) MRI
(c) NCCT/CECT
(d)PET/DSA
Routine blood investigation

Screening studies for pituitary lesion
 Hormone excess
serum prolactin
serum IGF-1
serum LH, FSH
serum A sub-unit
serum TSH
urinary 24 hr cortisol
 Hormone deficiency
serum cortisol
serum T4, free T3
serum testosterone (men)
serum estradiol (women)

Neurophthalmics of
Pituitary Adenoma

Neurophthalmics of Pituitary
Adenoma
OPTIC NERVE consists of 1.5 million fibres.
Total length is 5 cm of which 12-16 mm is
intracranial
Both optic nerves after coming out of optic canal
rise by 45 degrees and meet to form optic chiasm

Adenoma
Optic Chiasm can be
Prefixed 15%
Normal 70%
Post fixed 15%
With in the chiasm
• PMB lies in the middle
• Temporal hemi retinal fibers pass
ipsilateraly
• Nasal hemi retinal fibers decussate

Adenoma
Optic chiasm decussation
Inferior nasal fibers - anteroinferior
Superior nasal fibers - posterosuperior
PMB - in the middle primarily
posterosuperiorly

Adenoma
Enlarging pituitary adenoma may compress
Optic chiasm
Optic nerve in patients with postfixed chiasm
Optic tracts in patients with prefixed chiasm
3rd , 4th, 6th nerves with cavernous sinus extension
causing diplopia
Diplopia evaluation: 3 principles
• abnormal image is always peripheral
• is always from the paretic eye
• distance between the image increases on looking in the
direction of paretic muscle
Third ventricle compression leading to hydrocephalus

1. Blurred vision
2. Headache
3. Diplopia
4. Colour desaturation
5. Visual field defect
6. Optic atrophy
7. Post fixation blindness
8. Visual hallucination
9. See-Saw nystagmus
Adenoma: Chiasmal Syndromes

Adenoma
Visual evaluation in a case of pituitary
adenoma includes examination of:
 Visual acuity
 Colour vision
 Visual fields
 Opthalmoscopy
 Pupils
 Extraocular movements

Adenoma
VISUAL ACUITY
Eye’s ability to resolve details
Neurosurgically, patient’s best corrected visual acuity
is pertinent
Distant vision by Snellen’s chart placed at 6 metres
where accommodation is relaxed and light rays are
parallel
Near vision by Rosenbaum’s pocket chart held at a
distance of 14 inches

Adenoma
COLOUR VISION
• Loss of color vision precedes other visual
deficits
• In neurosurgical disease, red perception is
lost first described as red desaturation or red
wash outs
• Ishihara/hardy Ritter rand charts are used

Adenoma
Visual Fields
90 -100 deg temporally
60 deg nasally
50-60 deg superiorly
60-75 deg inferiorly
• With binocular vision, VF of both eyes overlap
• Visual fields are analyzed by
Confrontation method
Goldman’s perimeter
Humphrey’s field analyzer

 Bitemporal hemianopia
 Incongruous homonymous hemianopia
 Bitemporal central scotoma
 Diffuse scotoma
 Junctional scotoma
Visual Field Defects in Pituitary
Macroadenoma

 Classic defect in
pituitary adenoma
 Occurs in central
chiasmal defect
 Superotemporal field
affected first
↓
Lower temporal
field defect
Bitemporal Heminopia

 Occurs in optic tract
lesion
 Occurs in post.
Chiasmal lesion
 Compressing only the
macular fibers
Bitemporal central
scotoma
Incongruous
Homonymous
heminopia

 Central scotoma in one
eye with superotemporal
visual field loss in the
other eye
 Caused by compression
to anterior loop to the
decussating nasal fibers
in posterior optic nerve
(Von Wilbrand's knee)
Junctional Scotoma

Vessels emerge from nasal side of disc. Arteries are narrower than veins.
Optic disc appears pink with sharp margins and a cup-to-disc ratio of approximately
0.35. The vasculature is normal in course and caliber.

Neurophthalmics of Pituitary Adenoma
• Pituitary adenoma can cause primary optic
atrophy.
Primary Secondary
Colour of disc white grey
Border of disc Sharp Blurred
Arteries and veins Normal or reduced Arteries thin, veins
dilated
Distribution May affect one sector Entire disc affected
Causes Optic nerve/retinal
damage
Papillitis/papilledema
Lamina cribrosa visible Not visible

Bow tie atrophy Diffuse atrophy
Fundus Picture

Visual Evoked Potentials
Evoked electro physiological potential that
can be extracted using signal averages from
EEG activity recorded at the scalp.
Provides diagnostic information regarding the
functional integrity of visual system.
Measures the time taken for visual stimuli to
travel from eye to occipital cortex.
Particularly useful in infants

X-Rays
• Requires proper alignment of posterior
clinoid processes
 widening of sella
 destruction of sellar floor
 relation of median sphenoidal septum
 aeration of sphenoid sinus – conchal,
sclerotic, mixed

CT Head
CT HEAD is especially useful for:
Evaluating bony structures adjacent to
adenoma
Detecting calcifications in association with
macro adenoma
NCCT+ CECT head/sella with thin coronal cuts:
findings as seen in X-Rays
iso dense to adjacent brain parenchyma
intense contrast enhancement
calcifications uncommon (< 5%)
apoplexy- hyper density

CT HEAD
NCCT+ CECT head/ sella with thin coronal cuts:
Neck hyper extended(Reduces dental artifacts)
1.5 -2.0 mm cuts from tuberculum to dorsum sella
MICROADENOMAS
Focal hypo intensity
Increased vertical height
Asymmetrical convexity of superior surface
MACROADENOMAS
Isodense or heterogenous with mixed iso and hypo
areas intense contrast enhancement

MRI
 Better visualization of optic apparatus/carotids
 Multiplanar display
 Coronal images
Examining asymmetries
Minimal volume artifacts
 Sagittal images
Orientation of pituitary in relation to sphenoid sinus
 Axial images
Useful in lesions with parasellar extension
 Sensitivity for pituitary adenomas 90%
 Sensitivity post contrast 95%

• Sagittal and coronal T1WI sellar and parasellar
region with/without contrast 2.5mm thin
contiguous slices and 5mm slices axial T2WI of
whole brain.
• Normal pituitary is iso intense to gray matter on
T1WI with contrast enhancing
• Pituitary adenoma classified based on size:
microadenoma <10mm
macroadenoma >10mm
giant pit adenoma >40mm
MRI

MRI
Routine 1-2 Tesla MRI produce 2-3 mm
slices
Newer techniques : reduce false negatives
and can reduce acquisition time
I. Volume imaging techniques (3 –D Fourier
transform)
II. Fast spin echo

MRI
T1W
More sensitive
Better anatomical details of extra-axial
structures
Obtained in shorter time period
Normal anterior lobe is intermediate grey
Posterior lobe is bright
Paramagnetic contrast agents further
improve delineation

MRI
Microadenoma
• Seen as area of focal hypo-intensity
• Usually well defined, laterally situated
• Focal convexity upward
• Displacement of stalk to opposite side
• Relative hypo-intensity on immediate post
contrast sequences

Pituitary adenoma – relatively hypointense

MRI
Dynamic Imaging
• Consists of a series of images at the same location to
detect temporal changes in the signal intensity
• Dynamic contrast study done by 5 T1WI turbo spin
3mm thin slices repetitively at 20,40,60,80,100 sec
after 10ml contrast injection at 2ml/sec.
• Sequential coronal images at 20- 30 sec intervals
following contrast injection
• Micro adenoma enhance and wash out quickly as
compared to normal gland post contrast and hence
appear hypointense, deviation of stalk, bulging of
inferior and superior margin

Dynamic scan showing delayed contrast uptake by adenoma

MRI
Macroadenoma
Soft tissue sellar mass of intermediate signal
intensity on T1W images
Hyperintense on T2W
Enhancing diffusely on contrast
Superior spread most common
(Grows through diaphragma sellae - figure of 8
image )

Differential Diagnosis
Craniopharyngioma
Rathke’s cleft cyst
Meningiomas arising from tuberculum sella, planum
sphenoidale, anterior clinoid, posterior clinoid, medial
sphenoid wing
Aneurysms of cavernous/supraclinoid ICA, rarely
basilar top
Empty sella turcica
Chordomas
Dermoids/epidermoids
Metastasis especially in skull base

CRANIOPHYRNGIOMAS
Suprasellar location
On CT - heterogenous density
masses with areas of cyst
formation and calcification
Solid tissue is contrast
enhancing
On MRI variable signal
intensity lesions
Cysts are using high signal

GERMINOMAS
Seen usually in children
(pineal region)
When suprasellar midline in
location, behind infundibulum
Hypo on T1W, hyper on T2W,
contrast enhancing
Rathke’ cleft cyst
Anterior half of sella turcica
In front of pituitary stalk

PITFALLS
False negatives
• Especially with Cushing's disease in conventional
spin echo MRI
• Pneumatized anterior clinoid process
False positives
• Small pars intermedia cysts
• Clinically silent infarcts
• Foci of necrosis

Role Of Pet In Pituitary Adenoma
Primarily for monitoring treatment
11C-methionine and 18–FDG for metabolic
mapping.
Highest metabolic rate with prolactinoma
followed by growth hormone tumors.

Management - Hormonal overproduction
Prolactinoma:
Dopaminergic agonists
(bromocriptine,
cabergoline and
Quinagolide)
Growth hormone-secreting tumors:
Gonadotropin-secreting pituitary tumor:
Thyrotropin-secreting tumors
• Surgery, often followed by radiation
therapy.
• Medical treatment (Octreotide)
Nonsecretory pituitary adenomas
• Surgery
• If surgery is contraindicated,
medical treatment (Bromocriptine or Octreotide)

Management - Hormonal overproduction
Corticotropin-secreting pituitary tumors:
• surgery and radiation therapy
# Medical therapy:
• Central acting agents:
(bromocriptine, valproic acid, and cyproheptadine).
• Peripheral acting agents:
(ketoconazole, mitotane, and metyrapone).

Surgery Radiotherapy Medical
Non-functioning
adenoma
1st line 2nd line -
Prolactinoma 2nd line 2nd line 1st line
Acromegaly 1st line 2nd line 2nd line
Cushing’s
disease
1st line 2nd line -
Therapeutic Modalities Summary

Pituitary adenomas: Clinical, neuro-ophthalmic, radiological evaluation and medical management

Pituitary adenomas: Clinical, neuro-ophthalmic, radiological evaluation and medical management

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Pituitary adenomas: Clinical, neuro-ophthalmic, radiological evaluation and medical management