LEARNING OBJECTIVES

• Enumerate different types of pituitary

adenomas
• Define hyperpituitarism
• Enumerate causes of hyperpituitarism
• Define Gigantism
• Define acromegaly
• Describe Lab diagnosis of
Gigantism/Acromegaly
 Hyperpituitarism
• The increased secretion of one or more of the
hormones normally produced by the pituitary
gland.
 HYPERPITUITARISM
CAUSES
• Pituitary adenoma
• Pituitary Hyperplasia
• Carcinomas of the anterior pituitary
• Secretion of hormones by non pituitary
tumors
– Tumors  of the pancreas, lungs and adrenal
glands- produce GH or GHRH
• Certain hypothalamic disorders.
 Hyperpituitarism-causes
A benign, slow-growing anterior Pituitary
Adenoma - (Most Common Cause)
MANIFESTATIONS
 Headaches- with a lesion of any size
 Superior extension - visual loss, including
bitemporal hemianopias , superior or inferior field
defects, and central scotoma
 Elevated intracranial pressure
 Hypo-secretion of neighboring anterior pituitary
hormones
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 HYPERPITUITARISM - CAUSES
MASS EFFECTS
• Tumor extension into the cavernous sinus can
lead to cranial nerve dysfunction (commonly,
occulomotor (III ) and trochlear (IV) nerve
palsies.
• Lateral extension into the temporal lobe may
cause seizures. 

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 PITUITARY ADENOMAS -CLASSIFICATION

According to Cell Staining Characteristics

(acidophil, basophil, chromophobe cell
adenoma)
According to Size
Macroadenoma (>1 cm)
Microadenoma (< 1 cm )
Pituitary adenomas -Classification
CLASSIFICATION BASED ON FUNCTION
1.Functional
Associated with hormone excess and clinical
manifestations
2.Nonfunctioning
Silent and hormone-negative i.e.
immunohistochemical and/or ultrastructural
demonstration of hormone production at the
tissue level, without clinical symptoms of
hormone excess
 Pituitary adenomas -Classification

CLASSIFICATION BASED ON THE HORMONE(S)

PRODUCED BY THE NEOPLASTIC CELLS
• Detected by immunohistochemical stains
• Prolactin cell (lactotroph) adenoma most
common type of hyper-functioning pituitary
adenoma
• Growth Hormone cell (somatotroph)
adenoma - 2nd most common type of
hyper-functioning pituitary adenoma
 
• ACTH cell (corticotroph) adenoma

• TSH cell (thyrotroph) adenoma

• Gonadotroph Adenomas - hormone

negative adenomas ( so called "null cell
adenomas’’) or more correctly silent
gonadotroph adenomas
• Mixed (plurihormonal) adenomas:

Prolactin-GH mixed adenomas

(mammosomatotroph)-most common among
mixed adenomas
• Non functioning pituitary adenomas

– 25% of all pituitary tumors

 
 Pituitary Cell
Type & Hormone Tumor Type Associated Syndrome*
Lactotroph Prolactinemia, galactorrhea and
Lactotroph adenoma amenorrhea (females)
Prolactin Most common Forbes-Albright syndrome
Sexual dysfunction, infertility
(males)

Somatotroph Somatotroph Gigantism (children and

GH adenoma- adolescents)
2nd Most common Acromegaly (adults)

Mammosomatotr Mammosomatotro Combined features of GH and

oph ph adenoma prolactin excess
Prolactin, GH
Pituitary Cell Type
& Hormone
Tumor Type Associated Syndrome*
Corticotroph corticotroph adenoma Cushing syndrome
ACTH and other Nelson syndrome
POMC-derived
peptides

Thyrotroph TSH cell thyrotroph Hyperthyroidism

TSH adenoma

Gonadotroph Gonadotroph, "null Hypogonadism, mass

FSH, LH cell," effects, and
hypopituitarism
 ACROMEGALY & GIGANTISM
• Prolonged exposure to GH excess causes an
over­growth of the skeleton and soft tissue.
This occurs most commonly in adults and is
known as acromegaly.
• When GH excess is seen before long-bone
growth is complete, the condition is called
pituitary gigantism.
 ACROMEGALY & GIGANTISM
• Excess GH stimulates hepatic secretion of IGF-I,
which causes most of the clinical manifestations
of acromegaly:
• Acromegaly is characterized by GH
hypersecretion, multisystem-associated
morbidities, and increased mortality.
• Excessive GH secretion in adults is insidious in
nature and may not manifest with clear
diagnostic features.
 ACROMEGALY & GIGANTISM
CAUSES

–  Large hands and feet, tightening of rings or change of

shoes size
–  Coarsening of the facial features with frontal bossing
and prognathism (projection of the jaw)
–  Excessive sweating
–  Coexisting endocrinopathies, common in adults,
 ACROMEGALY & GIGANTISM
CAUSES
• Growth pattern in Gigantism
–  Dramatic linear growth acceleration in children.
–  Mild to moderate obesity accompanies tall
stature
–  The abnormal height growth typically precedes
or is concurrent with rapid weight gain in
children with GH excess.
– Progressive macrocephaly is also seen in children
with gigantism
 ACROMEGALY & GIGANTISM
CAUSES
• GH cell or somatotroph adenoma of the
pituitary gland (90 %).
• In a few patients, acromegaly is caused
by tumors of the pancreas, lungs, and adrenal
glands. These tumors lead to excess GH,
either because they produce GH themselves
or, more frequently, because they produce
GHRH
 ACROMEGALY & GIGANTISM
Clinicians should think of this diagnosis in
patients with 2 or more of the following
comorbidities:

• New-onset diabetes
• Acral and soft tissue overgrowth
• Diffuse arthralgias
• New-onset or difficult-to-control hypertension
• Cardiac disease
• Fatigue
• Prognathism
 ACROMEGALY & GIGANTISM
Clinicians should think of this diagnosis in
patients with 2 or more of the following
comorbidities:
• Head aches , Loss of vision - problems directly
related to the pituitary tumor size 
• Carpal tunnel syndrome
• Sleep apnea syndrome
• Progressive jaw malocclusion
 Acromegaly Diagnosis
• Laboratory investigations and imaging
techniques are generally used together to
confirm or rule out the presence of this
condition.
• The clinical diagnosis is often delayed because
of the slow progression of disease
 Acromegaly Diagnosis
Biochemical testing
 Random serum GH measurement
 Serum IGF-1 concentration
 Serum IGFBP-3 concentration
 Oral glucose tolerance test- Gold standard
Determining the source of excess GH
 Pituitary MRI
 Other studies
 Acromegaly Diagnosis
• Limitations of random serum GH measurements
• A single value of the growth hormone (GH) is not
useful in view of its pulsatality (levels in the blood
vary greatly even in healthy individuals).
• GH measurements are best determined as part of
dynamic testing that involves the use of
pharmacological or physiological provocative
stimuli to suppress or stimulate GH release
 INSULIN LIKE GROWTH FACTOR 1(IGF-1)
•  Most important of IGFs is IGF-1
•  The first line test for assessing growth hormone
for screening and treatment monitoring
• IGF-1 levels are lower in children, peak at
puberty, and gradually decline throughout
adulthood , reference values must, therefore, be
interpreted within the context of the patient`s
age.  
 IGF-1
• Pregnancy and puberty may be associated
with abnormally high IGF-1 level.
•  Malnutrition, hypothyroidism, or liver disease
may lower IGF-1 level even in patients with
acromegaly.
•  Most (approximately 80%) circulating IGF-1 is
bound to IGFBP3.
 Acromegaly Diagnosis
Serum IGF-1 concentration
• serum IGF-I concentrations do not fluctuate but
instead reflect integrated GH secretion during
the preceding day or longer.
•  Longer half life (18-20 h) than GH (15-20 min)
 and is elevated in virtually all patients with
acromegaly.
• It provides excellent discrimination from normal
individuals
 Acromegaly Diagnosis
IGFBP-3
•  Most abundant form of IGFBP
•  Main carrier of IGF in circulation
•  Promotes IGF mediated somatic growth
• IGFBP-3 is not a sensitive as IGF-1 but  If
IGF-1 and IGFBP-3 are combined,
sensitivity is increased
 Acromegaly Diagnosis
• Other pituitary hormone levels are measured
to assess the mass effect of the tumor on the
normal pituitary gland.
• An MRI of the brain focusing on the sella
turcica 
• CT scan offers less anatomic detail and is not
suggested, but it may be necessary if the
patient has a contraindication for MRI
(presence of a cardiac pacemaker)
 Acromegaly Diagnosis

GH SUPPRESSION TEST FOLLOWING AN

ORAL GLUCOSE LOAD
• It is a very specific lab test, will confirm
the diagnosis following a positive
screening test for IGF1 (somatomedin C)
 Acromegaly Diagnosis
GH SUPPRESSION TEST FOLLOWING AN
ORAL GLUCOSE LOAD

• The nadir GH suppression after administration of

glucose is considered the “gold standard” test for
acromegaly
 GH SUPPRESSION TEST FOLLOWING AN ORAL GLUCOSE LOAD

PRINCIPLE:
• GH secretion is part of the counter-regulatory
defence against hypoglycaemia and physiological
GH secretion is inhibited by hyperglycaemia.
• In acromegaly, or gigantism, GH secretion is
autonomous and does not suppress and may
paradoxically rise with hyperglycaemia.
 GH SUPPRESSION TEST FOLLOWING AN ORAL GLUCOSE LOAD

PREPARATION
• Patients should be advised to fast for 10
hours prior to this test but may drink small
volumes of water.
• Stress and/or exercise increases GH levels, so
the patient should be at complete rest for 30
minutes before the blood sample is drawn.
 GH SUPPRESSION TEST FOLLOWING AN ORAL GLUCOSE LOAD

REQUIREMENTS
• Adults: 75 g anhydrous glucose in cold water. The
solution should be chilled to improve palatability
• Children: the dose is weight related 1.75g/kg
body weight: the maximum load is 75g.
 GH SUPPRESSION TEST FOLLOWING AN ORAL GLUCOSE LOAD- 75g

• Insert an indwelling cannula and take blood

samples for baseline estimation of GH, IGF-
1 and glucose (1-2 mL in plain & 1-2 mL in
fluoride oxalate tubes)
• GH measurements be performed at baseline,
then every 30 minutes for a total of 120 minutes
after oral administration of 75g glucose
 GH SUPPRESSION TEST FOLLOWING AN ORAL GLUCOSE LOAD

SIDE EFFECTS
• Some subjects feel nauseated and may have
vaso-vagal symptoms during this test.
 Acromegaly Diagnosis
GH SUPPRESSION TEST FOLLOWING AN
ORAL GLUCOSE LOAD
• GH levels are suppressed <1 mIU/L or 1ng/ml in
normal individuals.
• Subjects with acromegaly fail to show this
suppression and about 50% of the patients show
paradoxical increase in GH concentration.
• The inability to suppress serum GH <1 mIU/L or
1ng/ml after glucose administration is considered
the diagnostic criterion for acromegaly
 Acromegaly Diagnosis
• Although GH levels are influenced by age, sex,
and weight, these variables are not taken into
account in the biochemical interpretation of
disease activity