●Anterior pituitary hormones and related drugs 316 ●Posterior pituitary hormones 318CHAPTER 42
THE PITUITARY HORMONES AND
RELATED DRUGS
puberty in order to optimize linear growth, and should continue
until growth ceases. Replacement therapy with gonadotrophin
or sex hormones is delayed until max-imum growth has been
achieved. Other indications are to increase growth in children
with chronic renal failure, with Prader–Willi syndrome and in
short children born short for gestational age. It is used in adults
with severe GH deficiency accompanying deficiency of another
pituitary hormone and associated with impaired quality of life.
In this setting it should be discontinued if the quality of life does
not improve after nine months of treatment. In adults aged less
than 25 years in whom growth is complete, severe GH defi-
ciency (e.g. following neurosurgery) should be treated with
somatropinuntil adult peak bone mass has been achieved.GROWTH HORMONE EXCESSOver-secretion of GH is usually associated with a functional ade-
noma of the acidophil cells of the adenohypophysis, and treat-
ment is by neurosurgery and radiotherapy. The place of medical
treatment is as an adjunct to this when surgery has not effected a
cure, and while awaiting the effect of radiotherapy, which can be
delayed by up to ten years. The visual fields and size of the pitu-
itary fossa must be assessed repeatedly in order to detect further
growth of the tumour during such treatment. Somatostatin low-
ers GH levels in acromegalics, but has to be given by continuous
intravenous infusion and also inhibits many gastro-intestinal
hormones.Octreotideandlanreotideare long-acting analogues
of somatostatin which lower somatotropin levels. They are given
by intermittent injection. Pegvisomantis a selective antagonist of
the GH receptor. It is a genetically modified GH analogue and is
injected subcutaneously once daily. It is used for acromegaly
with an inadequate response to surgery, radiotherapy and
somatostatin analogues. It has a range of gastro-intestinal, meta-
bolic, neurological and other adverse effects and should be
used only by physicians experienced in treating acromegaly.OCTREOTIDE
Uses
Octreotideis a synthetic octapeptide analogue of somatostatin
which inhibits peptide release from endocrine-secreting tumours
of the pituitary or gastro-intestinal tract. It is used to treat patientsANTERIOR PITUITARY HORMONES AND
RELATED DRUGSGROWTH HORMONE: PHYSIOLOGY AND
PATHOPHYSIOLOGYGrowth hormone (GH) is a 191-amino-acid protein secreted by
the acidophil cells in the anterior pituitary. Secretion occurs in
brief pulses, with a slower underlying diurnal variability, and
is greatest during sleep. Secretion is much greater during growth
than in older individuals. Secretion is stimulated by hypogly-
caemia, fasting and stress, and by agonists at dopamine, serotonin
and at α- and β-adrenoceptors. The serotoninergic pathway is
involved in the stimulation of somatotropin release during slow-
wave sleep. Secretion is inhibited by eating, by glucocorticos-
teroids and by oestrogens. The hypothalamus controls GH
secretion from the pituitary by secreting a GH-releasing hormone
(GHRH), somatorelin and a GH-release-inhibiting hormone,
somatostatin, which is also synthesized in D cells of the islets
of Langerhans in the pancreas. GH-secreting pituitary adenomas
cause acromegaly in adults (gigantism in children), whereas GH
deficiency in children causes growth retardation and short stature.
GROWTH HORMONE (SOMATROPIN):
THERAPEUTIC USESomatropin is the synthetic recombinant form of human
growth hormone used therapeutically. It promotes protein syn-
thesis and is synergistic with insulin. Its effect on skeletal
growth is mediated by somatomedin (a small peptide synthe-
sized in the liver, secretion of which depends on somatotropin).
Somatropinis used to treat children with dwarfism due to
isolated growth hormone deficiency or deficiency due to hypo-
thalamic or pituitary disease. This is often difficult to diagnose,
and requires accurate sequential measurements of height
together with biochemical measurements of endogenous GH
during pharmacological (e.g. insulin,clonidine,glucagon,argi-
nineorL-dopa) or physiological (e.g. sleep, exercise) stimula-
tion.Somatropintreatment also increases height in children
with Turner’s syndrome. Injections should start well before