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Anterior Pituitary Gland

Fawwaz Ammari
Laith & Hani
14 / 12 / 2009


Prof: Fawwaz Ammari

Lecture: anterior pituitary

Done By: Hani& laith

Anatomy of pituitary gland:

The pituitary gland is a small tiny endocrine gland
(about the size of a pea), lies in the base of the skull,
resting in a portion of sphenoid bone behind the nose
called sella turcica.
Look at the picture. In case of any tumor in the
pituitary gland, there will be destruction of the
sella turcica.
It is known as the master endocrine gland.
It consists of two lobes: anterior lobe (adenohypophysis) and posterior lobe
(neurohypophysis).
The size of the gland (which the anterior lobe consists 2/3) varies considerably.
It measures 15106 mml and weighs 500-900 mg.
It may double or triple in size during pregnancy.
-This may make it easier for the pituitary gland to get infracted in
case of low blood pressure.
-Just like the condition that may occur in a woman who has
severe postpartum hemorrhage, which is called (Sheehan
Syndrome or postpartum pituitary necrosis).
-Nowadays, this syndrome is very rare, recorded very rarely in
relatively old aged women.
Blood supply:
-The most richly vascularized of all mammalian tissues, receiving 0.8ml/min
from portal circulation.
-It is supplied by middle inferior and superior hypophysial arteries from the
internal carotid arteries.
Histology of pituitary gland:
Anterior pituitary cells were originally classified into groups according to their
affinities for histological stains:
Acidophils.
Basophils.
Chromophobes: non-functioning cells that are not stained by either acidic
or basic dyes.
Now with immunohistochemical and electromicroscopic techniques, cells are
classified according to their secretary products:
Somatotrophs:
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a. GH secreting cells
b. Acidophilic stained.
c. Account about 50% of anterior P.G (the majority).
Lactotrophic
a. Prl (prolactine) secreting cells.
b. Acidophilic stained
c. 10-15% of anterior PG
Thyrotrophis
a. TSH secreting cells
b. Basophilic cells
c. < 10% of anterior PG
Corticotrophs
a. ACTH secretary cells
b. Basophilic cells
c. 15-20% of anterior PG
Gonadotrophs
a. LH & FSH secretary cells
b. Basophilic staining
c. 10-15% of anterior PG.

Anterior pituitary hormones are

GH, PRL, TSH, ACTH, LH &
FSH.
*GH is important for growth and
development.
*PRL is important for lactation.
*TSH is important for stimulating
the thyroid gland to secrete
T3&T4.
*ACTH controls cortisol &
androgens synthesis and secretion
from the adrenal cortex. [*note:
aldosterone is mostly under the
control of renin-angiotensin
system].
*FSH & LH are important for testes and ovaries development, secondary sexual
characteristics and fertility.
Posterior pituitary hormones are vasopressin (anti-diuretic hormone -ADH) &
oxytocin.
-ADH is important for regulating body's retention and metabolism of water.
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-Oxytocin is important for uterine contractility during delivery and milk excretion
during breastfeeding.
In most of endocrine diseases, we either have excess or deficiency in hormone
secretion.
*Examples:
GH: [Excess acromegaly]- [Deficiency short stature and delayed growth].
PRL: [Excess Galactorrhea, infertility or loss of secondary sexual characteristics
(depending on the age)].
TSH: [Excess secondary thyrotoxicosis]- [Deficiency secondary
hypothyroidism].
ACTH: [Excess Cushing's disease]- [Deficiency secondary adrenal
insufficiency].
LH & FSH [Deficiency: Infertility and delayed puberty].
ADH: [Excess SIADH (syndrome of inappropriate ADH secretion)]. [Deficiency
diabetes insipidus].
*Now let's talk about hormonal deficiency of the pituitary gland or hypopituitarism.

*Hypopituitarism
It may present as single or multiple hormonal deficiency, [ i.e
Hypopituitrism is manifested by diminished or absent secretion of one or
more pituitary hormone].
The development of signs and symptoms is often slow and insidious; it may
take years before being diagnosed.
Hypopituitarism is either primary event caused by destruction of anterior
pituitary gland or secondary resulting from deficiency of hypothalamic
stimulating factors.
Treatment and prognosis depend on the extent of hypofunction, the
underlying cause and the location of the lesion.
Again.. It is usually gradual and may have single or multiple hormone
deficiency.
GH Deficiency
a. Deficiency in children (before epiphyseal closure): leads to short stature
and delayed growth.
b. Deficiency in adults: leads to vague non-specific symptoms, fatigue,
decreased muscle mass, loss of libido and increased risk of IHD but the
height of the patient isnt affected.

*Treatment: GH replacement therapy in adults to relieve different

manifestations and in children to restore normal height.
Gonadotrophin Deficiency (secondary hypogonadism or
hypogonadotrophic hypogonadism):
*This is different from primary hypogonadism (hypergonadotrophic
hypogonadism), which may happen in case of primary testicular or ovarian
failure. FSH & LH will be high but esrtadiol or testosterone will be low.
*in case of secondary hypogonadism all will be low.
In women (the presentation differs according to the disease time of
onset):
a. before puberty primary amenorrhea (no menses), failure of puberty
development (delayed puberty) and absence of secondary sexual
characteristics.
b. after puberty secondary amenorrhea and regression of secondary
sexual characteristics.
c. infertility.
In men:
a. before puberty: failure of puberty development (poorly developed penis
and testes) and absence of secondary sexual characteristics (no facial hair..).
b. after puberty: decreased libido or impotence, loss of secondary sexual
characteristic.
c. infertility.
TSH deficiency (leads to secondary hypothyroidism):
*TSH, T3 & T4 will be low.
*in primary hypothyroidism, TSH will be high, while T3 & T4 will be low.
Clinical features (they're the same in primary and secondary):

Cold intolerance.
Dry skin, loss of hair.
Mental dullness.
Constipation.
Increase in weight.
Bradycardia, slow reflexes.
Hoarseness, puffiness of the face.

 ACTH deficiency (leads to secondary adrenocortical insufficiency):

*Clinical features
Weakness
Nausea and vomiting
Anorexia
Weight loss
Postural hypotension and hyponatremia
*some manifestations of ACTH deficiency are a little bit different in
primary and secondary adrenal insufficiency.
*Hyper-pigmentation is only seen in case of primary adrenal
insufficiency (Addison's disease) and not seen in case of
secondary~. Why?
*In case of primary adrenal insufficiency (Addison's disease), there is
complete destruction of the adrenal cortex. Through feedback, reduced
cortisol level will lead to increased ACTH production, which will lead
to excessive pigmentation. [This occurs because melanocyte-stimulating
hormone (MSH) and adrenocorticotropic hormone (ACTH) share the
same precursor molecule, pro- opio-melano-cortin].
*In secondary adrenocortical insufficiency, however, patient may
develop hypo-pigmentation and may look pale.
*Postural hypotension and hyponatremia are 'more prominent'
in primary adrenal insufficiency (addisons), why?
-Because all layers of the adrenal cortex are destroyed, including the outer
layer (zona glomerulosa), which secretes aldosterone.
-In secondary adrenal insufficiency, aldosterone isnt affected; since ACTH
controls the inner (androgens secreting) and the middle (cortisol secreting)
zones of adrenal cortex, while the outer zone (aldosterone secreting) is
mainly controlled by renin-angiotensin system.
*So, remember.. aldosterone secretion remains largely intact in case of
secondary adrenal insufficiency.

**Causes of hypopituitarism:
Infarction: Postpartum necrosis (Sheehan syndrome)- vascular disease- head
trauma.
Infections: Tuberculosis-fungal infection- pyogenic- syphilis- toxoplasmosis.
Granulomas: Sarcoidosis - Histiocytosis.
Autoimmune lymphocytic hypophysitis (autoantibodies destroy pituitary gland
especially during pregnancy).
Neoplasm's involving pituitary
Pituitary adenoma, craniopharyngioma, metastasis or primary carcinoma (rare).
Aneurysm of internal carotid artery.
Hemochromatosis (patients who have hereditary types of anemia, such as betathalassemia, undergo multiple frequent blood transfusions; this may cause
secondary hemochromatosis where iron deposits accumulate in the pituitary gland).
Idiopathic or genetic
Deficient production of pituitary hormone or synthesis of abnormal hormone.
Iatrogenic: Stalk section- radiation therapy- hypophysectomy
Primary hypothalamic disorders
Tumor (craniopharyngioma)- Granulomas (histiocytosis x) - Genetic or idiopathic
releasing H.D- Head trauma- structural anomalies of hypothalamus.
In those cases we call it tertiary hypopituitarism.

**Diagnosis of pituitary deficiency by pituitary hormone stimulation test:

All hormones are released in a pulsatile manner, and mostly they are 'stress' hormones. So
hormones levels are different from minute to minute and from day to night (like cortisol level
which is in the early morning two times more than its level around midnight). *Always we
have to do what is called dynamic testing. as follows:
*When we have hormonal deficiency (like Addison's), we try to stimulate the hormone [so
we do stimulation test to confirm suspected deficiency].
*When we have hormonal excess (like cushing) we try to suppress the hormone [so we do
suppression test to confirm suspected excess].
*Dont memorize numbers in the following table!
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Hormone
GH

Stimulation test agent

I.H. test (insulin
induced
hypoglycemia test)
0.1 uint
L-dopa 250-500
Arginine 0.5 gm
Clonidine test
Glucagon test

N response
Serum GH > 10ng/ml at any
time

Notes
IH test is the Gold standard
method.

Prl

TRH 100-500
Metoclopramide

Doubling of baseline

*Dopamine is prl antagonist and

metaclopromide is dopamine
antagonis!

TSH

TRH 500 ng

Peak value >5 mu/ml

*Nowadays, we dont use

stimulation test for thyroid
because:
*Thyroid measurements are
enough for diagnosis.
*Thyroid hormones dont
fluctuate in their values; they
are fixed.
-

LH & FSH GnRH 100mmg IV

ACTH

I.H. TEST
(short ACTH
stimulation test
cosyntropin test)
Metyrapone test 2-3
gm po

Doubling of the base line

LH & FSH
serum cortisol >20 ng/dl
Serum 11-deoxycortisol
level >8 ng/dl

**Treatment of hypopituitrism
Treatment for life! (Except in GH deficiency: GH replacement therapy until the bone close.
After that, it may be harmful and may induce acromegaly).
Deficient hormone
Therapy
TSH
L-thyroxin .05-.02 mg/d PO
ACTH
Hydrocortisone 20 mg/ m-10mg /e
LH & FSH
Men :testosterone
Women :cyclic estrogen and
progesterone
(*)For fertility HCG, HMG
GH
0.05 mg/kg daily injection
(*) people with secondary hypogonadism have the chance to be fertile, while primary hypogonadism
patients dont have any chance!

* Pituitary tumors:
- Nearly always benign (i.e. adenomas)
- Account for 10% of intracranial neoplasm
* We have two types of adenomas:
-Pituitary microadenoma: intrasellar adenoma less than 1 cm in diameter.
-Pituitary macroadenoma: those larger than 1 cm in diameter.
- Pituitary microadenoma is more more common than pituitary macroadenoma.
*Type of pituitary tumors:

* As we can see, the most common pituitary tumor is Prolactinoma, the 2nd is nonfunctioning
pituitary tumor, 3rd is ACTH secreting adenoma, 4th is Growth hormone secreting
adenoma, 5th is Plurihormonal secreting adenoma (i.e. secrets different hormones) , 6th is LH
or FSH secreting adenoma , 7th is TSH secreting adenoma .
* When there's TSH secreting adenoma, then we'll have secondary thyrotoxicosis, but remember
that TSH-secreting adenoma is rare with less than 1% of all pituitary tumors.
* Clinical presentation of pituitary tumours:
- Nonsecretory pituitary tumors may grow slowly, destroying normal pituitary function
(hypopituitarism), or they may compress nearby structures and cause neurologic problems.
- Functioning pituitary adenomas can be clinically classified by means of the hormone they
elaborate. These tumors become symptomatic because they secrete hormones and they are

less likely than non-functioning adenomas to become large enough to compress adjacent
structures
- As pituitary tumors grow, destruction of normal pituitary tissue results in various hormonal
deficiencies.
- In rare cases, these tumors may spontaneously hemorrhage or become infracted.
- The pressure they exert on nearby structures can produce double vision and facial numbness.
* What's double vision ?
- Diplopia, commonly known as double vision, is the simultaneous perception of two images of
a single object.
- The optic chiasm is directly above the pituitary gland, and upward growth of pituitary
tumors frequently causes progressive visual loss. This visual loss typically begins from each
side of the field of vision and leads to tunnel vision and then blindness.
* What's tunnel vision?
- Tunnel vision is the loss of peripheral vision with retention of central vision, resulting in a
constricted circular tunnel-like field of vision.
Also, when the optic chiasm is affected by pituitary adenoma growth, Bitemporal
hemianopsia (or Bitemporal hemianopia) may occur.
* What's Bitemporal hemianopsia ?
Bitemporal hemianopsia (or Bitemporal hemianopia) is the medical description of a type of
partial blindness where vision is missing in the outer half of both the right and left visual
field. It is usually associated with lesions of the optic chiasm, the area where the optic nerves
from the right and left eyes cross near the pituitary gland.
NOTICE THAT pituitary adenomas can produce double vision, tunnel vision & bilateral
hemianopsia.
So, as in the slides, the clinical presentation is :
1-Hormone hypersecretion .
2- Space occupying lesion , this will lead to :
-- Headaches
--Visual loss (field defect)
3-Hormone deficiency states
-- Adenomas interfere with surrounding normal pituitary.
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* Tumours of the anterior pituitary can cause syndromes of hormone excess:

Tumours of the anterior pituitary can

cause syndromes of hormone excess
GH

Acromegaly

ACTH

Cushings disease

TSH

Secondary thyrotoxicosis

LH/FSH

(Non-functioning pituitary
tumour)

PRL

Prolactinoma

- The syndrome that's caused by LH/FSH hypersecretion is non-functioning macroadenoma of

the pituitary & its mentioned complications.
* KNOW THAT rare tumors secrete LH or FSH mainly (8% of all pituitary tumors).
- But when pituitary tumors compromise the secretory cells, the first evidence of cellular
failure usually affects the gonadotropins.
* prolactin hypersecretion will lead to symptoms of prolactinoma which are :
In women: it may cause amenorrhea, irregular periods, galactorrhea, infertility and osteoporosis.
In men: It may cause hypogonadism, loss of libido, and impotence.
Treatment of Pituitary Tumor
1) Surgical
* Transfrontal or transsphenoidal
-- The most common treatment for pituitary tumors is surgery. The success
of surgery depends on the tumor type, its location, its size, and whether the
tumor has invaded surrounding tissues.
-- The two main surgical techniques for treating pituitary tumors are:

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Endoscopic transnasal transsphenoidal hypophysectomy.With this

approach, a doctor usually can reach and remove the tumor through your nose
and sinuses without an external incision. No other part of your brain is affected,
and there's no visible scar. However, very large tumors may be difficult to
remove with this procedure, especially if a tumor has invaded nearby nerves or
brain tissue.

Transcranial (transfrontal) hypophysectomy. During this procedure, the

tumor is removed through the upper part of your skull by way of an incision in
your scalp. It's easier to reach large or more complicated tumors using this
procedure.

2) Radiological
* Conventional irradiation,heavy particle I
-- Radiation therapy uses high-energy X-rays to destroy tumors. It can be used after surgery or
alone as primary treatment if surgery isn't an option. Radiation therapy can be beneficial if a
tumor persists or returns after surgery and causes signs and symptoms that medications don't
relieve.
3) Medical
Dopamine agonist (bromocriptin)
Somastatin analog (octreotide)
-- Treatment with medications (drug therapy) may help to block excess
hormone secretion and sometimes shrink certain types of pituitary tumors:

Prolactin-producing tumors (prolactinomas). The drugs bromocriptine and

cabergoline can treat these types of tumors by decreasing prolactin secretion
and often reducing the size of the tumor. These drugs are often so effective in
treating these types of tumors that surgery isn't necessary.

Growth hormone-producing tumors. Drugs known as somatostatin analogs

(octreotide & others) cause a decrease in growth hormone production and may
decrease the size of the tumor.

If a pituitary tumor has resulted in decreased hormone production, or if

removal of a pituitary tumor has lowered hormone production, you may need to
take replacement hormones to maintain normal hormone levels.

KNOW THAT the 1st choice treatment for prolactinoma is medical treatement not surgery,
unless the tumor is so large.

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* Now the Dr. moved to the next slide group & the 1st slide is a reminder of what we've said:

Anterior pituitary hormone

overproduction

GH ------leads to acromegaly & gigantism

Prl -------lead to hyprerprolactinemia

ACTH---lead to cushing disease

TSH -----lead to 2ndary thyrotoxicosis

* ACTH hypersecretion will lead to cushing's syndrome & it's the most common cause of
endogenous cushing's disease (70-75% of cases).
* What's the difference between gigantism & acromegaly?
-- Gigantism

is Excessive growth, especially in height, resulting from overproduction during

childhood or adolescence of growth hormone by a pituitary tumor. Untreated, the tumor
eventually destroys the pituitary gland, resulting in death during early adulthood.
- If the tumor develops after growth has stopped, the result is acromegaly, not gigantism.
-Acromegaly is a chronic disease of adults marked by enlargement of the bones of the
extremities, face, and jaw that is caused by overactivity of the pituitary gland after puberty or
closure of the bone epiphyses.

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NOTICE THAT The exact order of pituitary adenomas is: 1st Prolactin secreting adenoma, 2nd
non-functioning adenoma, 3rd GH secreting adenoma. But when we talk about functioning
adenomas GH is the 2nd after Prl secreting adenoma.
* This slide talks about the clinical feature of Acromegaly& the percentage of each:

Clinical feature

Symptoms
Acralenlargement
Hyperhidrosis
Lethargy or fatigue
Weight gain
Paresthesia
Joint pain
Papillomas
Photophobia
Hypertrichosis

%
100
100
88
87
70
69
45
46
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* From the slide above we can NOTICE THAT:

-- The most important clinical feature is Acral enlargement (100% of patients)
Acral: relating to, or affecting peripheral parts, such as limbs, fingers, or ears.
- For example: each time this person buys a shoe he changes his size to a larger one...
-- Other important feature is hyperhidrosis.
* Hyperhidrosis means excessive sweating.
* The Dr read all the clinical feature of acromegaly that are mentioned in the slide.
*Papilloma is a benign epithelial tumor forming a rounded mass.
* Hypertrichosis means a condition of excessive hairiness either all over the body or covering a
particular part.
* What's the difference between Hirsutism & Hypertrichosis?
Hirsutism is mainly in females due to androgens hypersecretion, so we see excessive hairiness
in the androgen dependant hair areas.
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*Other features and clinical symptoms of acromegaly:

Clinical features 2
Symptoms
Goiter
Hypertension
Cardiomegaly
Renal calculi
Hyperinsulinemia
Glucose intolerance

%
32
24
16
11
70
50

:: NOTES::
-- Renal caliculi occurs because there's excess Ca secretion.
-- hyperinsulinemia which means that those patients have DM or impaired glucose tolerance test.
* In this picture you can see the hand of patient with acromegaly at the left compared with normal
hand at the right.

Q: patient with gigantism, can his case followed by acromegaly after puberty if excessive
hormone secretion persists?
Ans : yes .

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** An example of this case is this picture:

* Also in this slide u can see a case of acromegaly: (read the chief complaints)

Patient #

50 year old male

Chief complaints:

Fatigue
sweating of hands and
feet
Increasing shoe size
Joint pains
Headache

- Notice his large head, nose, mouth, protruding of the jaw (v.imp) etc.

* Also in the next picture you can see a case of acromegaly :

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Acromegaly
Frontal Bossing

Chin Protrusion

:: NOTE:: the frontal bossing & chin protrusion.

* in these pictures you can see hands of acromegaly :

* Dr said that we call hands of acromegaly spider hands.

* This's a protruded large tongue of acromegaly:

NOTICE THAT A patient

with marked macroglossia
could have severe sleep
apnea which can be
associated with cardiac
arrhythmias and sudden
death.

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* In this slide we can see papillomas or skin tags of acromegaly :

* The changes of acromegaly are slow and gradual ; you can see this by following the
patients in these 2 photos:

What are the Laboratory findings in patient with acromegaly?

1) Plasma glucose may be elevated (because of diabetes)
2) Increase serum insulin (because of insulin resistance)
3) Elevated serum phosphate
4) Hypercalciuria (excretion of calcium will be increased)
5) Elevated GH
* these lab results are not sufficient for the diagnosis because when we deal with hormonal
abnormality we need what we call dynamic testing, in which we suppress hormone secretion
when there's hypersecretion & stimulate hormone secretion when there's hyposecretion.
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* So, in the diagnosis we do glucose suppression test, because there's hyperglycemia.

* Diagnosis of acromegaly:
-- Glucose suppression test
-- Measurement of IGF-1(insulin-like growth factor)
--Tumor localization by MRI.
* In this slide you can see how the glucose suppression test goes in acromegalic patient:

Oral Glucose Tolerance Test

Acromegaly

GH
Upper
Normal

Control
0

30

60
90
Time (minutes)

1200

* In the control person you can see that suppression takes place, but in acromegalic patient this'll
not happen.
Treatment of acromegaly
-- All patient needs therapy to prevent complication and to halt the progression of the disease
-- The objective of therapy ( need experienced surgeon )
- removal of the pituitary tumor
- reversal of GH hypersecretion
- maintenance of normal pituitary gland
Surgical : surgery done by 2 methods :
--transsphenoidal
--transfrontal
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- And this depends on the site of the tumor.

-- Radiotherapy is successful in 60-80% conventional irradiation in dose of
4500-5000 rad
Medical
octreotide effective in 65%
bromocriptine is less effective
Pegvisomat is a GH recptor antagonist.

Prolactinoma
- The clinical presentation depends when the prolactinoma takes place, before puberty or after
puberty:
-- Before puberty: it'll delay puberty.
-- After puberty: as we said before:
In women: it may cause amenorrhea, oligomenorrhea, irregular periods, galactorrhea( in 70%),
infertility and osteoporosis.
In men: It may cause hypogonadism, loss of libido, impotence and galactorrhea(rare in males).
* Know this slide:

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* causes of hyperprolactinemia are :

Causes of hyperprolactinemia 2

Disease states
prolactinomas
hypothalamic and pituitary stalk disease
granuloma,craniopharyngioma,
primary hypothyroidism
chronic renal failure
cirrhosis
chest wall trauma

* When prolactin level is in hundreds think of prolactinoma, which's in general the most

important cause of hyperprolactinemia.

* When prolactin level is around 40-50, then you have to check thyroid function test, because in

this case the most likely is primary hypothyroidism (because TSH is a stimulant for insulin
secretion)
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Laboratory finding
- Elevated serum prolactin
- Decrease plasma gonadotropin
- Liver function test
- Kidney function test
- TFT (thyroid function test)

Treatment
--Surgical
-transsphenoidal
-transfrontal
--Medical
- Dopamine agonist :
-bromocriptine
-cabergoline the most effective & can shape the tumor size causes shrinkage of the tumor.
*As we said before medical treatment is the 1st choice in treating prolactinoma unless there's
pressure symptoms produced by the tumor.

Done By: Hani Eid & Laith Anani good luck in OSCE exam...
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