THE

HYPOTHALAMO-
HYPOPHYSIAL
AXIS
SALAKO O. P
OUTLINE

•BACKGROUND
•BRIEF ANATOMY
•HYPOTHALAMIC HORMONES
•ANTERIOR PITUITARY HORMONES
•POSTERIOR PITUITARY HORMONES
•DISORDERS OF THE HYPOTHALAMO-
HYPOPHYSIAL AXIS
•REFERENCES
BACKGROUND

01 02 03
There are different The endocrine system The endocrine system
ways through which is one of the major is predominantly
the body systems of controlled by the
communicates with communication in the hypothalamo-
itself body. hypophysial axis
ANATOMY OF THE HYPOTHALAMIC-
PITUITARY AXIS
THE HYPOTHALAMUS
• The hypothalamus is a part of diencephalon which lies below the thalamus. It forms the floor and
the lower parts of lateral walls of the third ventricle.
• Anatomically the hypothalamus is small in size weighing only 4 g and forming only 0.3% of the
total brain mass but physiologically there is hardly any activity in the body that is not influenced
by it. Thus, the functional significance of the hypothalamus is disproportionate to its size.
• The hypothalamus controls three systems: (a) autonomic nervous system, (b) endocrine system,
and (c) limbic system.
• The hypothalamus contains different nuclei that regulates these functions
• The dominant nuclei that is associated with endocrine functions are the arcuate nuclei,
the paraventricular nuclei and the supraoptic nuclei
HYPOTHALAMIC HORMONES
Corticotropin-releasing hormone (CRH);

Thyrotropin-releasing hormone (TRH);

Growth hormone-releasing hormone (GRH);

Growth hormone-inhibiting hormone (GIH), now generally called SOMATOSTATIN;

Gonadotropin-releasing hormone (GnRH);

Prolactin-inhibiting hormone (PIH) [Dopamine].

ANATOMY OF It is also called the hypophysis
THE
HYPOTHALAM It weighs about 0.5 - 1g and is slightly heavier in
IC- females.
PITUITARY AX
It is located at the base of the brain in the Sella
IS turcica.
(The Pituitary
Gland) It is divided into the anterior and posterior lobes
which have different embryological origins.
 ANATOMY OF THE HYPOTHALAMIC-
PITUITARY AXIS
Arterial twigs from the carotid
The anterior lobe of the
The Pituitary gland is arteries and circle of Willis
pituitary gland is linked to the
connected with the form a network of fenestrated
hypothalamus by the
hypothalamus by the pituitary capillaries called the primary
hypothalamic–hypophysial
stalk or hypophyseal stalk. plexus on the ventral surface
portal system.
of the hypothalamus

The capillaries drain into the

sinusoidal portal hypophysial
Posterior pituitary hormones
vessels that carry blood down
It is a true portal system are transported via axons to
the pituitary stalk to the
the posterior pituitary gland.
capillaries of the anterior
pituitary.
 ANTERIOR PITUITARY GLAND
HORMONES
1
• Growth Hormone

2
• Prolactin

3
• Thyroid-stimulating Hormone (TSH)

4
• Adrenocorticotropic Hormone (ACTH)

5
• Follicle-stimulating Hormone (FSH)

6
• Luteinizing Hormone
GH secretion is usually increased by:

Onset of sleep
stress,
 Hypoglycemia ( e.g In response to the falling plasma glucose
concentration about an hour after meals )
exercise,
fasting,
increased circulating amino acid,
 protein diet,
 glucagon, etc.
Regulation
of Growth
Hormone
PROLACTIN
Factors that increase Prolactin secretion include:
• Estrogen (pregnancy),
• suckling,
• sleep,
• stress,
• Thyrothropin releasing hormone, etc.

Factors that decrease prolactin secretion include:

• Dopamine,
• Bromocriptine,
• Somatostatin, Prolactin, etc
The HPA
Axis
(Hypothalam
o-Pituitary-
Adrenal)
The HPT Axis
(Hypothalamo-
Pituitary-
Thyroid Axis)
The HPG Axis
(Hypothalamo-Pituitary-Gonadal Axis)
POSTERIOR PITUITARY
HORMONES
DISORDERS OF THE
HYPOTHALAMO-
HYPOPHYSIAL AXIS
AND THEIR
ASSOCIATED
INVESTIGATIONS
BASIC PRINCIPLES

Diseases of the hypothalamo-pituitary axis are usually characterised by

excess secretion or deficiency of the associated hormones.
01
If a specific organ is the target of any of the hypothalamo-
hypophyseal hormones, pituitary disorders are usually regarded as
secondary while hypothalamic disorders are regarded as tertiary.
02
Simultaneous measurement of both the trophic hormones and their
controlling factors, whether hormones or metabolic products, may
be more informative than the measurement of either alone.
 BASIC PRINCIPLES
An apparently ‘normal’ hormone result should be interpreted in the context of
the associated hormone axis.

It may be difficult to distinguish between deficient releasing factor and a

primary deficiency of pituitary hormone secretion

Isolated hormone deficiencies are more likely to be of hypothalamic than of

pituitary origin. The coexistence of diabetes insipidus suggests a hypothalamic
disorder.
 • Suppression tests are used mainly for the
differential diagnosis of excessive hormone
secretion. The substance (or an analogue) that
normally suppresses secretion by negative
feedback is administered and the response is
BASIC measured.

PRINCIPL • Stimulation tests are used mainly for the

differential diagnosis of deficient hormone
ES secretion. The trophic hormone that normally
stimulates secretion is administered and the
response is measured. A normal response
excludes an abnormality of the target gland,
whereas failure to respond confirms it.
BASIC PRINCIPLES
• Excessive secretion usually involves a single hormone, but deficiencies are
often multiple.

• However, many pituitary tumours are non-secretory and may present

clinically with mass effects (eye signs or headaches).

• Laboratory tests establish only the presence or absence of hypopituitarism,

and the cause must be sought by other clinical means such as radiological
imaging
GROWTH HORMONE EXCESS
- ACROMEGALY & GIGANTISM
• Most patients with GH excess have acidophil adenomas of the anterior
pituitary gland, which may be secondary to excessive hypothalamic
stimulation
• The clinical manifestations of GH excess depend on whether the condition
develops before or after fusion of the bony epiphyses.
• Gigantism is caused by excess GH secretion in childhood before fusion of the
epiphyseal plates
• Acromegalic features may develop after bony fusion, but these patients may
die in early adult life from infection or cardiac failure or as a consequence of
progressive pituitary tumour growth.
Acromegaly
Gigantism
 • The diagnosis of Growth hormone excess
is confirmed by demonstrating a raised
plasma GH concentration that is not
suppressed by a rise in plasma glucose
GLUCOSE concentration.
SUPPRESSIO • Procedure:
• After an overnight fast, insert and
N TEST FOR intravenous cannula.
SUSPECTED • After at least 30 minutes, take basal
samples for plasma glucose and GH
ACROMEGA estimation
LY • Patient is given 75g of glucose dissolved
in 300mL of water
• Take samples for glucose and GH at 30,
60, 90 and 120 minutes after glucose
load.
• In normal subjects, plasma GH concentrations fall to very low levels –
to below 1 microgram/L after a 75 g oral glucose load after 2/2.5
hours.

• In acromegaly, the secretion of GH is autonomous and this fall may

not occur or be only slight, or there may even be a paradoxical rise.

• Growth hormone secretion is inhibited by hyperglycaemia in the

normal subject.
Failure to suppress may also be seen in some patients with severe
liver or renal disease, in heroin addicts or in those taking levodopa.
Fasting plasma GH can be normal in 8 per cent of acromegalic
patients.
This test is unnecessary in patients who are known diabetics.

Plasma IGF-1 has a long half-life and may be used in screening for
acromegaly.
TREATMEN • The aim of treatment is to bring basal
GH levels to a fall greater than
T FOR 1microgram/L in response to
ACROMEGA increased glucose concentrations.

LY Surgical – Trans-sphenoidal surgery

Medical – bromocriptine or
cabergoline (dopamine receptor
agonists) or somatostatin analogue;
Octreotide or lanreotide, which bind
to somatostatin receptors, can be
used or pegvisomant (GH receptor
antagonist)
Radiation therapy
 • Severe deficiency of GH in children before
growth is completed results in retarded
growth and pituitary dwarfism.
GROWTH • Most commonly due to inherited autosomal
recessive disorder. Other causes include:
HORMONE Pituitary adenoma, Craniopharyngioma,
DEFICIENC Infarction and trauma to the pituitary
• Clinical features include: proportionate
Y retardation in growth of bones, normal
mental state for age, poorly-developed
genitalia, delayed puberty and episodes of
hypoglycaemia
Diagnosis of Growth Hormone Deficiency

• The clinical history should include information about birthweight and

whether intrauterine growth retardation was an issue.
• A low plasma IGF-1 concentration may be a useful screening test.
Ensure to take sample when blood Growth hormone levels are not
expected to rise, so as not to give a false positive.
• Urinary GH excretion, either in 24-h collections or timed overnight,
may offer a relatively safe screening test.
 In the investigation of suspected GH deficiency
there are
many stimuli to choose from including
Investigations hypoglycaemia,
arginine infusion, L-dopa administration ,
of Growth exercise, and sleep.
Hormone
Deficiency
The safest and most commonly used tests are
exercise provocation, multiple sampling
during sleep (with an indwelling venous
catheter), and serum IGF-1 estimations.
• In the 'sleep' procedure blood samples are collected at 30-minute intervals for
3-4 hours after the onset of sleep; a peak value of at least 10 mU/L occurs in
the normal subject but not in the GH deficient patient.

• In the exercise test the patient is subjected to very hard physical exercise
(such as running up and down a flight of stairs or use of a bicycle ergometer
so as to generate a pulse rate of >150/min), and blood is collected at 0, 2, and
20minutes after cessation.

• A normal response is a GH rise to above 20 mU/L or to > 10-fold the basal

level
 • Excessive production of prolactin, most
commonly by lactotroph (PRL-
secreting) adenoma, also called
prolactinoma.
• This is an important cause of
amenorrhoea, sexual dysfunction,
osteoporosis, infertility.
HYPERPROLACTIN • High plasma prolactin concentrations
inhibit the normal pulsatile release of
AEMIA GnRH and inhibit gonadal steroid
hormone synthesis directly --
galactorrhea and decreased libido,
failure to ovulate and amenorrhea
• Hyperprolactinaemia can result from
hypothalamic inhibition of PRL
secretion by certain drugs (e.g.
chlorpromazine, reserpine and
methyldopa).
Causes of
Hyperprolactinemi
a
Evaluation
• Prolactin Levels in serum can indicate the cause.
• Tumours usually give values in excess of 100 ng/mL. Values in excess of 200 ng/mL, in the
absence of renal failure, are strongly indicative of a PRL-secreting tumour .

• A raised plasma prolactin level should always be confirmed by a repeat analysis on a

fresh specimen, collected without stasis or stress.
HYPOPITUITARISM

• Hypopituitarism is a syndrome of
deficiency of pituitary hormone
production that may result from
disorders of the hypothalamus,
pituitary or surrounding structures

Deficiency of pituitary hormones

causes hypofunction of the target
endocrine glands
HYPOPITUITARISM

• Clinical features of deficiency are usually absent until about 70 per

cent of the gland has been destroyed.

• Hyperprolactinaemia - amenorrhoea and infertility may be early

symptoms

• It could be a pan hypopituitarism or partial hypopituitarism.

CAUSES OF
HYPOPITUITA
RISM
Suspicion of Anterior Pituitary Hypofunction

• Clinical and radiological evidence of a pituitary or localized brain tumour.

• Hypogonadism,
• Adrenocortical insufficiency
• Short stature caused by GH deficiency,
• Hypothyroidism.

• Gonadotrophins are often the first to decrease in hypopituitarism.

• it is unusual for the post-pituitary hormones such as ADH and oxytocin to be affected
Investigations
of
Hypopituitaris
m
• Investigation of the pituitary------CT/MRI

• Combined pituitary stimulation test-- (insulin or glucagon plus TRH

and GnRH given as one test)
TREATMENT OF HYPOPITUITARISM

This consists of specific therapy A glucocorticoid, for example

depending on its cause and may hydrocortisone in the acute
include surgical removal of a large situation or prednisolone for
adenoma. maintenance.

Gonadotrophin deficiency may

Adrenal replacement should require testosterone in males and
precede T4 therapy to avoid an oestrogen replacement in women,
Addisonian crisis with or without progesterone as
appropriate.
CONCLUSION
• The Hypothalamo-Pituitary axis is quite
germane in the regulation of the body's
functions

• Disorders along this axis could either be

from the hypothalamus or the pituitary
gland.

• Having a good understanding of the HPA axis

is crucial to correctly diagnosing the
disorders along this axis.
 Clinical Biochemistry and Metabolic Medicine, Martin Crook

A Textbook of Medical Physiology, Guyton and Hall

REFERENC https://www.upjs.sk/public/media/22834/The%20Hypothalamus%20and%20the%20Pituitary%20Gland.pdf

ES Dr Balogun Ujeh : HYPOTHALAMIC & PITUITARY HORMONES

Dr Fasua Tosin : The hypothalamus and pituitary gland AND DISORDERS.

THANK YOU