Table 5.

5 Treatments of acromegaly
Advantages

Disadvantages

Transsphenoidal surgery - common first-line Rapid effect

Can restore
compression

vision

in

optic

Invasive

nerve

and

requires

general

anaesthetic

Non-curative for large, extrasellar tumours

Might be curative if complete resection

May cause hypopituitarism by damage to other cell types
Somatostatin analogue drugs - lower growth hormone (GH)
Non-invasive

Monthly intramuscular injection (most commonly)

May shrink large extrasellar tumours

Expensive, may lower chance of curative surgery for intrapituitary

lesions

Decreases GH in 60% of patients

Gastrointestinal side-effects (commonly diarrhoea)

Radiotherapy - a good second or third line Noninvasive

Likely
levels

to

shrink

tumour

and

Might be curative

reduce

GH

Unlikely to be curative, i.e. continuous therapy needed

Slow to act - may take up to 10 years

Likely to cause hypopituitarism by destroying other pituitary cell types
Mildly increases risk of cerebrovascular disease

Case history 5.2

A 40-year-old woman had attended her family doctor for a cervical smear. She saw a new
doctor, her previous doctor having known her since childhood. The new doctor was concerned by the patients
coarse facial appearance and asked some questions. The woman was
surprised to be asked about her shoe size but confirmed that most of her shoes were now a size larger than 10
years ago.
What diagnosis is being considered?
What other questions should be asked?
What specific features of the examination should be sought? What tests would
confirm the doctors suspicion?
Answers, see p. 97

tary hormone deficiencies following surgery

or radiotherapy to the anterior pituitary (Box
5.6).
Any pituitary space-occupying lesion can
cause
loss of somatotrophs and GH deficiency. In
childhood, this may be a craniopharyngioma; in
adults,

most likely a non-functioning adenoma. Other

childhood
causes
include
congenital
deficiency
(Figure 3.9; review Box 3.6) or cranial
irradiation
for CNS tumours or haematological malignancy.
In
adults, loss of GH secretion is part of
physiological

82 / Chapter 5: The hypothalamus and pituitary gland

Box 5.6 Symptoms and signs of

growth hormone deficiency

190
180
97
90
75
50
25
10
5

170
160
150

M
F

140
130
120
110
100
90
80
70
60

Growth
hormone

50

Decreased stature/cessation of growth

(childhood)
Decreased exercise tolerance
Decreased muscle mass and strength
Increased body fat/decreased lean body
mass
Centripetal fat distribution, increased
waist:hip ratio
Hypertension and ischaemic heart disease
Decreased left ventricular mass
Dyslipidaemia [increased low-density
lipoprotein (LDL)-cholesterol]
Osteoporosis
Poor quality of life

1 2 3 4 5 6 7 8 910111213141516171819
Age (years)

Figure 5.9 Short stature due to growth hormone

(GH) deficiency and the effect of GH replacement.
The height of a girl is shown compared to the
reference growth charts, where the population is split
into centiles (i.e. 50% of girls heights lie below the 50th
centile line, 5% below the 5th, etc.). Her height for
chronological age () is greatly reduced, but
skeletal maturity (or bone age) is also delayed. As a
consequence, height plotted for bone age ( ) falls within
the centiles of normality. Bone age is
determined by radiological examination of the left
hand. Comparison is made with standard radiographs
to assess skeletal maturity. Serum GH was
undetectable in a basal sample and no secretion
could be elicited by dynamic testing. Secretion of
other anterior pituitary hormones was normal. After
GH replacement was initiated, there was rapid
catch-up of both height and skeletal maturity. M
and F represent maternal and paternal height
respectively.

ageing and may be partly responsible

for some of the changes in body
composition associated with ageing, but
does not usually produce obvious clinical symptoms.
If GH is lacking, try to stimulate it;
lack
of
GH
is diagnosed by stimulation testing
alongside
identifying a low serum IGF-I value (see

Figure
5.7
and Table 5.4). It is treated by the daily
subcutane-

Girls height (cm)

ous injection of recombinant GH (oral

peptides
would be degraded in the intestine). In
children
with true GH deficiency, this results in a
spectacular
clinical effect, with a small child growing
slowly
into a normally sized adult. It is also
used
by
paediatric endocrinologists to treat short
stature
of
other
causes
(e.g.
Turner
syndrome/45,XO).
Administration of GH in adequate dose
will
make
any child grow more quickly in the short
term,
but
does not necessarily increase final
height.
The benefit of treatment in adulthood
remains
contentious
amongst
clinicians
as
improvements
for individual patients can be minimal.
Treatment

is
also
relatively
expensive
and
invasive;
thus,
it
is important to demonstrate clear
patient
benefit
from GH replacement. At present, UK
guidelines
include a quality-of-life questionnaire
generating
an Assessment of Growth Hormone
Deficiency
in
Adults (AGHDA) score and clear
biochemical
evidence of GH deficiency (see Table 5.4).
From
the
clinicians perspective, improvement in
fasting
lipid
analysis would also be persuasive for
continuing
replacement therapy. In clinical trials,
studies
have
reported extensive benefits:
Improvements in fat mass
Decreased waist-to-hip ratio and lower
visceral fat
Increased lean body mass
Increased bone mineral density

Chapter 5: The hypothalamus and pituitary gland / 83

Increased muscle mass and strength

Increased maximal exercise
performance
Increased VO2max, maximum power
output, maximum heart rate and
anaerobic threshold
Increased left ventricular mass,
stroke volume, cardiac output and
resting heart rate with decreased
diastolic blood pressure
Increased red cell mass
Increased emotional reaction and
improved social isolation scores
Increased perceived quality of life
Increased self-esteem
Decreased sleep requirement
Prolactin
Human prolactin (PRL) is secreted by
the
lactotroph cells in the anterior pituitary and
comprises 199 amino acids with three
disulphide bonds. By weight, outside of
pregnancy or breast-feeding, the PRL
content of the normal human pituitary
gland is 1% that of GH.
Effects and mechanism of action
Prolactin plays some role in stimulating
growth
of
the alveolar component of breast tissue
during
adolescence. However, its major action is to
stimulate
breast
milk
production
(lactation)
(Figure
5.10;
also
see the endocrinology of pregnancy in
Chapter
7,
Box 7.16). Following childbirth and the
consequent
decrease in maternal serum oestrogen
and
progesterone, PRL in the presence of cortisol
initiates
and
maintains lactation. Its loss results in the
immediate
cessation of milk secretion. PRL also
inhibits
synthesis and release of LH and FSH by the

anterior
pituitary gonadotrophs. This causes a
physiological
secondary amenorrhoea (see Box 7.17)
that
acts
as
a natural contraceptive in the postpartum
period.
In birds, the hormone stimulates
nest-building
activity and crop-milk production; in
reptiles,
amphibians and some fish, it acts as an
osmoregulator. These wider functions and the
conservation
of
PRL-like molecules across species have
led
to
other
actions being attributed to PRL in both
male
and
female humans. However, for many of
these
proposed functions, the physiological
significance
remains unclear (Figure 5.10). Like
GH, PRL

signals through specific receptors that

dimerize and recruit tyrosine kinase
signalling pathways (review Chapter 3
and Figure 3.8).
Regulation of production
The principles and features of PRL
regulation
are
similar to those of GH. PRL from
lactotrophs
is
under tonic inhibition by dopamine, with
TRH
providing a stimulatory input (Figure
5.10).
Stress
increases serum PRL. Although the peaks
are
not
as
discrete as for GH, PRL is also released
episodically
with highest levels during sleep. The most
profound
changes in serum PRL occur during
pregnancy
and
lactation. The concentration increases
progressively,
up to 10-fold, through pregnancy,
possibly
in
part
because of rising oestrogen levels. It
remains
elevated
during lactation under the stimulus of
suckling,
an
example of a positive feedback loop:
prolactin
stimulates milk production, consumed by
suckling,
which
in turn by a neural reflex stimulates
further
prolactin

release. The loop is only broken once the

baby
stops
suckling.
Clinical disorders
Hyperprolactinaemia
Symptoms and signs
Increased
serum
PRL
causes
oligomenorrhoea
or
secondary
amenorrhoea (see Box 7.17), or subfertility in women of reproductive age by
inhibiting the normal pulsatile secretion
of LH and FSH, and the mid-cycle LH
surge, leading to anovulation. When
present, inappropriate breast milk
production
(galactorrhoea)
is
striking.
Hyperprolactinaemia
occurs
with
sufficient frequency to be relevant to
the primary care physician. The
underlying cause is commonly a
microprolactinoma. Other causes are
listed in Box 5.7 (Case history 5.3).
In contrast, men and post-menopausal
women
tend to present later when the underlying
pathology
is more likely to be a larger
macroadenoma,
and
presenting symptoms and signs may
reflect
the
consequences of a space-occupying lesion
(see
Box
5.1).
Men with hyperprolactinaemia may also
present
with gynaecomastia or features of
secondary
hypogonadism (see Box 7.10).