causing expulsion of the fetus and the

placenta.
In
this role progesterone appears to antagonize
and
oestrogen potentiate the uterine response to
oxytocin. Post-partum in the mammary gland,
oxytocin causes contraction of the myoepithelial
cells
surrounding the alveoli and ducts to expel
milk
from the breast.
Like vasopressin, oxytocin circulates
largely
unbound and so is removed rapidly by the
kidney
(t1/2 5 min).
Outside
parturition
and
breastfeeding,
it
circulates
in
very
low
concentrations
and
is normally undetectable in the blood.
Oxytocin
binds to its cell-surface G-protein-coupled
receptor
and
signals
intracellularly
via
phosphatidylinositol
metabolism and calcium (review Figure
3.16).
Regulation of production
The movement of the fetus down the birth
canal
is
an example of positive feedback in
endocrinology
(review Chapter 1). Oxytocin stimulates
uterine
muscular contraction which moves the fetus
into
the distending vagina, which in turn sends
neural
inputs back to the brain to enhance oxytocin
secretion. This positive feedback loop is only
broken
once the fetus is expelled. Other factors, such
as
the
fall in progesterone and the presence of
oestrogen,
may play a minor part in regulating oxytocin
release.
Similarly, positive feedback regulates
oxytocin
release during breast-feeding. Suckling of the
nipple

causes release of oxytocin and leads to

ejection of milk. Even the sight and sound of
an infant can stimulate milk ejection.
Stimulation of oxytocin secretion ceases
once the baby stops suckling.
Clinical disorders
Endocrine syndromes of oxytocin excess and
deficiency have not been described. However,
increased oxytocin appears to improve
behaviour in autism spectrum disorder.

Key points
GH, PRL, ACTH, FSH, LH and TSH are
the major hormones of the anterior
pituitary
Oxytocin and vasopressin are the major
hormones of the posterior pituitary
Pituitary tumours, especially nonfunctioning adenomas, are very common
Hormone overactivity secondary to
tumour formation can cause wellrecognized endocrine syndromes
Always consider local structural damage
and compression from pituitary tumours
Underactivity of the anterior pituitary
tends to affect multiple hormones

Answers to case histories

Case history 5.1
The patient has bitemporal hemianopia. This
is caused by loss of function of optic nerve
fibres; the only point where pressure can
cause this distribution of visual field loss is at the optic
chiasm.
The most likely pathology at this location is
upward growth of a pituitary tumour.
The best imaging modality is MRI. In an emergency
setting, CT can be useful, but the resolution from MRI
is much better for
intracranial structures.

If a pituitary space-occupying lesion is

detected, the patient should be referred
urgently to an endocrinologist for two
reasons: first, a prolactinoma will almost
certainly shrink with dopamine agonist
therapy with restoration of vision (see clinical section
on prolactin); and second, with
pituitary tumours, it is critical to think of what
hormone function may have been lost by
local pressure on pituitary cell types. Most
importantly, the patient may be hypoadrenal because
of loss of ACTH secretion (see
Chapter 6) and hypothyroid (see Chapter 8)

Chapter 5: The hypothalamus and pituitary gland / 97

from TSH deficiency. In an emergency

setting (e.g. if the patient has presented
unconscious and hypotensive and a large
pituitary mass has been detected),
hydrocortisone should be administered
intravenously.
Case history 5.2
The diagnosis under consideration is
acromegaly. Its insidious nature means that
those who know the patient well frequently
miss it.
Questions should address symptoms and
signs relating to GH excess (see Box 5.5). In
addition, are there any symptoms or signs
from loss of other pituitary hormones (e.g.
hypoadrenalism or hypothyroidism) or a
local mass effect? A sensitive question would
interrogate potential loss of the menstrual
cycle. Facial photographs should be sought
from the previous 10-20 years.
In addition to the features listed in Box 5.5,
examination should look for potential visual
field defects or diplopia.
Serum IGF-I should be measured. A 75g
OGTT should be considered or a serum GH
day series conducted.

represent co-secretion of PRL by the tumour. It

is more likely to indicate a small degree of
stalk disconnection.
The patient should be placed on daily
hydrocortisone, then thyroid hormone, and
programmed for urgent transsphenoidal
surgery to debulk the tumour and relieve
pressure on the optic chiasm. Vision might
be permanently lost if surgery is delayed.
Surgery is highly unlikely to be curative and
suitable secondary treatments include
somatostatin analogues and/or radiotherapy.
Case history 5.5

The differential diagnosis of

hyperprolactinaemia is given in Box 5.7. The
presence of poor growth and tiredness
suggests hypothyroidism.
A thyroid function test showed a markedly
raised serum TSH with low T4.
The lack of thyroid hormone feedback to
the pituitary had led to an increase in TRH
which, in turn, had promoted growth of
lactotrophs. Once this stimulus was
removed by restoration of thyroxine negative
feedback on TRH, the pituitary enlargement
regressed.

The man has SIADH. Although Addison

disease might be considered in view of the
hyponatraemia, the plasma osmolality is low.
The SIADH is secondary to pneumonia,
although an underlying lung malignancy
cannot be excluded as a contributory factor.
After taking samples of sputum and blood
for microbiology, antibiotics should be
started and fluid intake restricted to 1 L over
the next 24 h with close attention paid to
urine output and haemodynamic status, e.g.
pulse and blood pressure. Tachycardia and
hypotension would argue for highdependency care.
Other investigations directly related to his
symptoms include arterial blood gas
assessment (with oxygen given if the patient is
hypoxic), chest X-ray and sputum analysis for
tuberculosis and malignancy.
In this case, fever settled rapidly with
antibiotics, the patient remained
haemodynamically stable, serum sodium
rose within 12 h to 132 mmol/L (132 mEq/L)
and, on continuing the same management,
normalized 36 h later. Other symptoms
gradually improved. No evidence was
obtained for lung malignancy and
electrolytes were normal at discharge.

Case history 5.4

Case history 5.6

The patient has secondary hypothyroidism

and hypoadrenalism from the pituitary mass.
The PRL is minimally raised but is unlikely to

The history needs to focus on the CNS for

previous trauma or infection and specific
symptoms such as headache. Questions

Case history 5.3

98 / Chapter 5: The hypothalamus and pituitary gland

need to exclude renal damage. A drug

history and family history are required for
agents or inherited syndromes that cause DI.
The patient should be admitted for a water
deprivation test. This test needs strict
monitoring as it can be dangerous (see
Table 5.6) and patients with psychogenic
polydipsia are known to cheat (taps may
need to be isolated from mains water). An

alternative if available might be serum

vasopressin
measurement
following
hypertonic saline.
DI is either cranial (relating to the
hypothalamus and posterior pituitary) or
nephrogenic (distal convoluted tubule of the
kidney), reflecting deficient vasopressin
production or action.