Block Endocrine System, Metabolism, and

Disorders

THE PITUITARY
GLAND

AND DISORDERS
Dr. Made Ratna Saraswati,
SpPD
Faculty of Medicine, Udayana
University, 2009

Further reading
David G Gardner, Dolores Shoback.
Greenspans Basic and Clinical
Endrocrinology 8th ed. Lange.
McGraw Hill 2007.
Harrisons Principles of Internal
Medicine 17th ed. McGraw Hill 2008.

(Part 15 Endocrinology and Metabolism)

Anatomy

The pituitary gland lies on the base of

the skull in a portion of the sphenoid
bone called the sella tursica.
Anterior pituitary is the most richly
vascularized of all mammalian tissue
(0.8 ml/g/min).

Fig. Anatomic relationships and blood

supply
of the pituitary gland

Greenspans Basic and Clinical Endrocrinology 8th ed.

Fig. Venous drainage of the pituitary gland

Greenspans Basic and Clinical Endrocrinology 8th ed.

Hypothalamic nuclei produce hormones

that traverse to the portal system and
impinge on anterior pituitary cells to
regulate pituitary hormone secretion.
Posterior pituitary hormones are derived
from direct neural extensions.

Fig. Diagram of hypothalamic pituitary

vasculature

Neuroendocrine
cell nuclei

Superior
hypophyseal
artery
Long portal
vessels
Trophic
hormone
secreting cell

Anterio
r
Pituitar
y

Hypothalam
us

Stalk
Inferior
hypophyseal
artery

Posteri
or
Pituitar
Short portal
y
vessels

Harrisons Principles of Internal Medicine, 17th

The hypothalamic
hormones

The hypothalamic hormones can be

divided into:

those secreted into hyppophysial portal

blood vessels
those secreted by the neurohypophysis
directly into the general circulation.

The hypophysiotropic hormones

regulate the secretion of anterior
pituitary hormones, include:

Growth hormone-releasing hormone

(GHRH)
Somatostatin
Dopamine
Thyrotropin-releasing hormone (TRH)
Corticotrophin-releasing hormone (CRH)
Gonadotropoin-releasing hormone (GnRH).

The anterior pituitary

hormones

The six major anterior pituitary

hormones are:

Adrenocorticotropic hormone (ACTH)

Growth hormone (GH)
Prolactin (PRL)
Thyroid-stimulating hormone (TSH)
Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH)

The anterior pituitary is often

referred to as the master gland
because, together with the
hypothalamus, it orchestrates
the complex regulatory functions
of multiple other endocrine
glands.

Fig. Diagram of
pituitary axes

Harrisons Principles of Internal

Medicine, 17th ed. p. 2196

The posterior pituitary

hormones

Antidiuretic hormone (ADH)

Oxytocin

Hormonal feedback regulatory

systems

The hypothalamus and pituitary gland

form a unit which exerts control over the
function of several endocrine glands:
thyroid, adrenal, and gonads, as well as
a wide range physiologic activities. This
unit constitutes a paradigm of
neuroendocrinology: brain-endocrine
interactions

Fig. Feedback regulation of endocrine axes

Feedback control, both

negative and positive,
is a fundamental
feature of endocrine
system.
Each of the major
hypothalamic pituitary hormone axes
is governed by
negative feedback, a
process that maintains
hormone levels in the
normal range

Harrisons Principles of Internal

Medicine, 17th ed. p. 2192

Hormonal rhythms

The feedback regulatory systems are

superimposed on hormonal rhythm
that are used for adaptation to the
environment,
i e: seasonal changes, daily
occurence of the light-dark cycle,
sleep, meal, stress, etc.

Fig. The hypothalamic-pituitary-adrenal

axis, ilustrating negative feedback by
cortisol (F)

Greenspans Basic and

Clinical Endrocrinology 8th
ed. Lange, 2007. p. 114

Essentially all pituitary hormone rhythm

are entrained to sleep and to the
circadian cycle, generating reproducible
patterns that are repeated
approximately every 24 hours.

Recognition of this rhythm is important

for endocrine testing and treatment.

Fig. The episodic, pulsatile pattern of ACTH

secretion and its concordance with
cortisol secretion in healthy human
subject during the early morning

Greenspans Basic and Clinical Endrocrinology 8th ed.

Fig. Sleep associated changes in prolactine

(PRL) and growth hormone (GH)
secretion in human

Greenspans Basic and Clinical Endrocrinology 8th ed.

Peak levels of GH occur during sleep

stages 3 or 4;
The increase in PRL is observed 1 -2
hours after sleep begins and is not
associated with a specific sleep phase.

Pituitary and
Hypothalamic
disorders

Hypothalamic and pituitary

lesions present with a variety of
manifestations, including:

pituitary hyper- and hyposecretion

sellar enlargement
visual loss.

Etiology
In adult, the most common cause of
hypothalamic and pituitary
disfunction is pituitary adenoma (the
great majority is hypersecreting)
In children, the most frequent lesions
causing hypothalamic and pituitary
disfunction is craniopharyngioma,
and other hypothalamic tumor.

Early manifestations

The earliest symptoms of such tumors are

due to endocrinologic abnormalities, the
most frequent manifestation: hypogonadism.
Endocrine disturbance manifestation in
children: low GH level, delayed puberty,
diabetes insipidus).
Endocrinologic problem precede sellar
enlargement and local manifestation
(headache, visual loss) which are late
manifestation (seen in patient with larger
tumors or suprasellar extension)

Common and later

manifestations

Pituitary hypersecretion
Pituitary insufficiency
Enlarged sella tursica
Visual field defect
Diabetes insipidus

1. Pituitary hypersecretion

PRL hypersecretion is the most common

endocrine abnormality due to hypothalamicpituitary disorders, and PRL is the hormone
most commonly secreted in excess by pituitary
adenoma.
GH-secreting adenomas are second in
frequency to prolactinoma and cause the
classic syndromes of acromegaly and
gigantism.
ACTH hypersecretion leads to Cushings
disease

2. Pituitary insufficiency

Panhypopituitarism is a classic
manifestation of pituitary adenoma (but
only present in less than 20% of cases
because of earlier diagnosis)
The earliest manifestation in adult:
hypogonadism secondary to elevated
levels of PRL, GH, or ACTH and cortisol
In children the most frequent clinical
manifestation is short stature (GHdeficiency should be considered).

3. Enlarged sella tursica

May cause by: pituitary adenoma or

empty sella syndrome
Other less common cause:
craniopharyngioma, lymphocytic
hypophysitis, carotid artery aneurysm
Evaluation should include pituitary
function: PRL, thyroid, and adrenal
function.

4. Visual field defect

Manifestation: bitemporal hemianopsia,

unexplained visual field defect, or visual
loss considered to have hypothalamic
or pituitary disorders until proved
otherwise.
In addition to visual field defect, large
pituitary lesion may extend laterally into
the cavernous sinus, compromising the
function of the third, fourth, or sixth
cranial nerve, leading to diplopia.

5. Diabetes insipidus

DI is a common manifestation in
hypothalamic disorder but rare in
primary pituitary lesions.

Pituitary Adenoma
Prolactinoma is the most common type
(60%)
GH hypersecretion (20%)
ACTH excess (10%)
Hypersecretion of TSH or the gonadotropin
are
unusual
Pituitary
microadenoma = intrasellar
adenoma <1cm
Pituitary macroademo

Fig. Pituitary adenoma

Coronal T1weighted
postcontrast MR
image shows a
homogeneously
enhancing mass
(arrowheads) in
the sella tursica
and suprasellar
region compatible
with a pituitary
adenoma; the
small arrows
outline the carotid
arteries
Harrisons Principles of Internal Medicine, 17th

Treatment
1.
2.
3.

Surgery
Irradiation
Drug to supress hypersecretion
by the adenoma or its growth

Fig. Transsphenoidal resection of pituitary

mass via the endonasal approach

Harrisons Principles of Internal Medicine, 17th

Acromegaly and
Gigantism
GH hypersecretion is usually the result
of a somatotrope adenoma, but may
rarely caused by extrapituitary lesions

Presentation and diagnosis

Manifestation of GH and IGF-1 hypersecretion

are indolent and often are not clinically
diagnosed for 10 years or more.
Acral bony overgrowth result in frontal bossing,
increased hand and foot size, mandibular
enlargement with prognathism, and widened
space between the lower incisor teeth.
In children and adolescent, initiation of GH
hypersecretion prior to epiphyseal long bone
closure is associated with development of
pituitary gigantism,

Soft tissue swelling: increased heel

pad thickness, increased shoe or glove size,

ring tightening, characteristic coarse facial
features, including hyperhidrosis, deep and
hollow sounding voice, oily skin,
arthropathy, kyphosis, carpal tunnel
syndrome, proximal muscle weakness and
fatigue, acanthosis nigricans, and skin tags.
Generalized visceromegaly occurs
including cardiomegaly, macroglossia, and
thyroid enlargement.

Fig. Features of
acromegaly/gigantism
A 22 year-old man with
gigantism due to excess
growth hormone is shown
to the left of his identical
twin. The increased height
and prognathism of the
affected twin are apparent.
Their clinical features
began to diverge at the
age of 13 years.
Harrisons Principles of Internal Medicine,
17th ed. p. 2210. Journal: R Gagel, IE
McCutcheon, N Engl J Med 324:524;1999.

Enlarged hand and foot

Laboratory investigation

Age and gender matched serum IGF-1 levels

(elevated)
Failure of GH supression to <1 g/L within 1 2 h of oral glucose load (75g)
Ultrasensitive GH assay (nadir GH <0,05
g/L)
PRL should be test (25% with elevated PRL)
Thyroid function, gonadotropin, and sex
steroid may be attenuated because of tumor
mass effects.

Vasopressin insufficiency:

Diabetes

Insipidus

DI is the excretion of a large volume of urine

(diabetes) that is hypotonic, dilute, and tasteless
(insipid).
Patient present with polyuria, the 24 hours urine
volume is >50 ml/kg body weight, the osmolarity
is <300 mosmol/L
Other cause of polyuria such as osmotic diuresis
that occur in diabetes mellitus or intrinsic renal
disease must be excluded.

The major effect of ADH is to increase

the water permeability of the luminal
membrane of the collecting duct in the
kidney.
Diabetes insipidus is a disorder resulting
from deficient ADH action and is
characterized by the passage of
amounts of very dilute urine.

GROUP DISCUSSION

Case 1: a woman with

increasing shoe size

A 40 year old female has noticed an increase in

her shoe size from 38 to 42, and her weight also
increased from 68 to 80 kg. Her menstrual
period has stopped 6 months ago. She also
complained of acne on her face.
Physical examination found her 158 cm, blood
pressure 140/80 mmHg. Neck demonstrated
diffuse thyromegaly, but the TSHs and FT4 test
was normal. Her face demonstrated thickening of
the nasolabial fold and prominence of the
supraorbital ridge. Compare to her picture 5
years before, her face showed a striking change
in facial feature. She did not show hirsutism. Her
hands and feet had a rubbery consistency.

Assignment:

What is the most likely disorder of this

woman?
What may cause this disorder?
What laboratory and radiology test
would you do for the patient to workup
the diagnosis?
Is she has thyroid problem? Why?
Why she stopped menstruating?

Self assessment:
1. Explain the hypothalamus pituitary
target organ axis
2. Summarize the course and the condition
associated with pituitary adenoma,
including prolactinoma, acromegaly,
gigantisme, growth hormone deficiency.
3. Summarize the normal physiologic
hormone function of posterior pituitary
4. Describe the clinical features of diabetes
insipidus

THANK YOU