Hyposecretion of Anterior Pituitary Hormones Flashcards
What is the term given to decreased secretion of ALL anterior pituitary hormones?
Panhypopituitarism
What is Sheehan’s syndrome? Explain its pathophysiology.
This is specific to WOMEN
Specifically describes post-partum hypopituitarism secondary to hypotension (caused by post partum haemorrhage - PPH)
During pregnancy, there is an increase in lactotroph cell number (lactotroph hyperplasia) for breastfeeding - the increase in size of the pituitary gland means it is more metabolically active
Lack of blood flow to the pituitary gland (ischaemia) due to hypotension leads to pituitary infarction (tissue death) as the increased metabolic demands are not being met
What is pituitary apoplexy?
Intra-pituitary haemorrhage or (less commonly) infarction (i.e. tissue death)
Why is a single measurement of most hypothalamic hormones not useful?
Most hypothalamic hormones tend to be released in pulses
What type of test do you do to test if someone is producing a hormone?
Stimulation/provocation test
How are the releasing hormones administered in these tests?
Intravenous
What is the name given to the secondary endocrine gland failure that results from a lack of corticotrophin release from the pituitary?
Hypoadrenocorticalism
What are the effects of a lack of GH (somatotrophin) in children and in adults?
Children – short stature (=2 SDs < mean height for children of that age and sex)
Adults – loss of GH effects are uncertain
State some genetic and acquired causes of GH deficiency in children.
Genetic:
Deficiency of hypothalamic GHRH
Mutations of GH gene
Developmental abnormalities (e.g. aplasia or hypoplasia of the pituitary gland)
Acquired:
Tumours of the hypothalamus and pituitary
Other intracranial tumours nearby (e.g. optic nerve glioma)
Irradiation
Head injury
Infection or inflammation
Severe psychosocial deprivation
What are most endocrine-related causes of short statue due to (with reference to the HP axis)?
Decreased production of GHRH
As well as being its own hormone, GH stimulates the production of other hormones. State one important hormone that is stimulated by GH, its side of production and its effects.
IGF I = insulin-like growth factor I
It is produced in the LIVER
It mediates growth effects
What type of dwarfism is caused by a GH receptor defect?
Laron Dwarfism
Describe the IGF I levels in people with this type of dwarfism.
LOW IGF I
Because functioning GH receptors are necessary for GH to stimulate the production of IGF I
Why are the Pygmies in Africa naturally short?
Their IGF I doesn’t function properly
Using GnRH as an example. State and describe two examples of tertiary hypopituitarism.
Kallmann’s Syndrome
Hypogonadism + Anosmia
Genetic defect where the neurones in the embryo that will go on to produce GnRH are unable to migrate to the hypothalamus
So they have a hypothalamus that lacks GnRH neurones
The defect also affects the migration of neurones involved in olfaction (which causes anosmia)
Prader-Willi Syndrome
Hypogonadism is one of the aspects of this disorder and the problem is at the level of the hypothalamus
What is the gold standard method of testing the ability of the pituitary to release growth hormone?
Insulin-induced hypoglycaemia
Hypoglycaemia is a potent stimulus for growth hormone release
State three other triggers for an increase in GH release.
Arginine
Glucagon (seems odd as this increases blood glucose but it turns out that in people who have GH deficiency, glucagon is good at stimulating growth hormone release)
Exercise
Describe how the insulin-induced hypoglycaemia test is used to test GH secretion.
In a normal subject, the insulin-induced hypoglycaemia will give a massive rise in GH secretion
If you have a partial deficiency of GH then your response will be reduced
For each of the following anterior pituitary hormone deficiencies, state the replacement used and the parameter that is monitored during treatment: ACTH TSH Women - LH/FSH Men - LH/FSH GH
ACTH: Give hydrocortisone (cortisol drug) Monitor serum cortisol TSH: Give thyroxine Monitor serum T4 Women – LH/FSH: Give oestradiol (E2 - an oestrogen) and progestogen (a substance which binds to and activates the progesterone receptor) Monitor libido and oestrogen deficiency Men – LH/FSH: Give testosterone Monitor libido and serum testosterone GH: Give GH Monitor IGF I (because GH stimulates IGF I production by the liver)
State some of the effects of growth hormone therapy in children.
Increased linear growth
Decease in body fat
Younger children respond better
Obese children respond better
What is a problem with growth hormone therapy in children?
Tolerance may develop so you need to think about when to start GH therapy
How is the human recombinant GH used in GH therapy administered and how frequently must it be given?
Subcutaneous or Intramuscular
It is given daily or 4/5 times a week
Describe the absorption, metabolism and duration of action of the drug.
It has a maximal plasma concentration after 4-6 hours
Metabolism – renal and hepatic with a short half-life (20 mins)
Duration of action – it works on protein synthesis so it’s duration of action is going to be quite long.
IGF I levels peak after around 20 hours
State some adverse effects of GH therapy.
Lipoatrophy at the site of administration Intracranial hypertension
Headaches (due to intracranial hypertension)
GH is also a cell stimulation hormone so there is an increased risk of tumours
State some signs and symptoms of GH deficiency in adults.
Decreased muscle mass Increased adiposity Increased waist: hip ratio Decrease HDL and increased LDL Reduced muscle strength and bulk Impaired psychological wellbeing and quality of life
How can you diagnose GH deficiency in adults?
Lack of response to GH stimulation test (e.g. insulin-induced hypoglycaemia)
Low plasma IGF I
Low plasma IGF-BP3
