Hyposecretion of Anterior Pituitary Hormones Flashcards
What is the difference between primary, secondary and tertiary endocrine gland disease?
Primary – problem with the endocrine gland/hormone released
Secondary – problem with the pituitary gland/hormone released
Tertiary – problem with the hypothalamus
What is the term given to decreased secretion of all anterior pituitary hormones?
Panhypopituitarism
Requires deficiency in GH and at least one other AP hormone
Broadly speaking, what can panhypopituitarism be caused by?
Congenital defects (rare) Gene mutations (more rare)
In what order does loss of secretion occur?
Usually develops in adults with progressive loss of pituitary secretion Gonadotrophins GH Thyrotrophin Corticotrophin Prolactin
What are three main types of panhypopituitarism?
Simmond’s Disease
Sheehan’s Syndrome
Pituitary Apoplexy
Describe the onset of Simmond’s disease and state some of its causes and symptoms.
Insidious (slow) onset Can be caused by: Infiltrative diseases Craniopharyngioma Cranial injury Pituitary adenomas Following surgery Symptoms: (mainly due to loss of adrenal, gonadal and thyroid function) Impotence Loss of libido Hypotension Tirednesss Secondary amenorrhoea or oligomenorrhoea Loss of body hair Waxy skin
State the cause of Sheehan’s syndrome and describe its onset.
This is specific to WOMEN
It is caused by vasoconstrictor spasm of hypophysial arteries as a result of post-partum haemorrhage
This spasm causes pituitary infarction
This develops very RAPIDLY
What is pituitary apoplexy? Describe its onset.
This is similar to Sheehan’s syndrome but isn’t specific to women
It is caused by intra-pituitary infarction or haemorrhage This also has a RAPID presentation
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 somatotrophin in children and in adults?
Children – stunted growth (pituitary dwarfism)
Adults – loss of GH effects are uncertain
State some other causes of short stature.
Genetic - Down’s, Turners, Prader Willi
Malnutrition
Emotional deprivation
Endocrine disorders - cushing’s, hypothyroidism, GH def, poorly controlled T1DM
Systemic disease - CF, RA
Malabsorption - coeliac disease
Skeletal dysplasia - osteogenesis imperfecta, achondroplasia.
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, GH deficiency is secondary to to hypothalamic dysfunction.
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:
a. ACTH
b. TSH
c. Women - LH/FSH
d. Men - LH/FSH
e. GH
a. ACTH Give hydrocortisone Monitor serum cortisol b. TSH Give thyroxine Monitor serum T4 c. Women – LH/FSH Give ethinyloestradiol and medroxyprogesterone (HRT) Monitor libido and oestrogen deficiency d. Men – LH/FSH Give testosterone undecanoate Monitor libido and serum testosterone e.GH Give GH Monitor IGF I
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
What are the potential benefits of GH therapy in adults?
Improved body composition
Improved muscle strength and exercise capacity Normalisation of HDL-LDL
Increased bone mineral content
Improved psychological and mental wellbeing and quality of life
What are the potential risks of GH therapy in adults?
Increased risk of cardiovascular accidents
Increased growth of soft tissue e.g. cardiomegaly
Increased susceptibility to cancer
Give a cause of congenital panhypopituitarism
Mutations of transcription factor genes needed for normal anterior pituitary development e.g. PROP1 mutation
Presents with:
Short stature
Hypoplastic AP on MRI
What happens to anterior pituitary during pregnancy that makes it vulnerable to infarct in Sheehan’s syndrome?
AP enlarges
Lactotroph hyperplasia
Thus blood supply/demand is increased during this period.
What is the presentation of Sheehan’s syndrome?
Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
Failure of lactation – prolactin deficiency
Failure to resume menses post-delivery
Posterior pituitary usually not affected
What can precipitate pituitary apoplexy?
Anti-coagulants.
What is achondroplasia?
mutation in fibroblast growth factor receptor 3
Abnormality in growth plate chondrocytes - impaired linear growth
Average size trunk
Short arms and legs
