1 - Hyposecretion of anterior pituitary hormones Flashcards
What are primary and secondary endocrine diseases?
primary - problem with the endocrine gland/hormone released
secondary - problem with the pituitary gland/(stimulating) hormone released
Define hypopituitarism and panhypopituitarism
Decreased production of ALL anterior pituitary hormones (PANhypopituitarism) or of specific hormones
Broadly speaking, what can panhypopituitarism be caused by?
Most likely to be acquired Congenital defects (rare) Gene mutations (more rare)
Give some causes of panhypopituitarism?
- tumours - craniopharyngiomas, adenomas, metastases and cysts
- radiation (GH is the most vulnerable and TSH is resistant)
- infection - meningitis
- traumatic brain injury
- infiltrative disease (infiltrates the pituitary stalk) e.g. sarcoidosis
- inflammatory - hypophysitis
- pituitary apoplexy
- post-partum infarction (Sheehan’s syndrome)
In what order does loss of pituitary secretion occur?
Gonadotrophins GH Thyrotrophin Corticotrophin Prolactin
What are the symptoms of someone who has developed panhypopituitarism through gene mutation of the PROP1 gene?
- deficient in GH and at least 1 other anterior pituitary hormone
- short stature
- hypoplastic pituitary on MRI
What are three main types of panhypopituitarism? Briefly describe what they are
- > Simmond’s Disease - panhypopituitarism
- > Sheehan’s Syndrome - postpartum hypopituitarism secondary to hypotension/postpartum haemorrhage
- > Pituitary Apoplexy - intra-pituitary infarction of haemorrhage
Describe the onset of Simmond’s disease and state some of its causes
onset is insidious
Can be caused by: • Infiltrative diseases • Craniopharyngioma • Cranial injury • Pituitary adenomas • Following surgery
What are the symptoms of Simmond’s disease?
(mainly due to loss of adrenal, gonadal and thyroid function)
• Impotence - GnRH
• Loss of libido - GnRH
• Secondary amenorrhoea or oligomenorrhoea - GnRH
• Fatigue - ACTH/TSH
NOTE: deficiency of GH has less of an impact in adulthood, because you have fully grown
State the cause of Sheehan’s syndrome
in pregnancy, lactotrophs become very enlarged (high prolactin) and the pituitary becomes very large. The anterior pituitary is hanging by a very thin stalk. During delivery women have a large postpartum haemorrhage., and hence the pituitary will become deprived of a decent blood supply.
Ischaemia and necrosis of the pituitary.
How does Sheehan’s syndrome present?
- failure of lactation (no prolactin)
- lethargy/anorexia/weight loss - deficiency of TSH/ACTH/GH
- failure to resume menses post delivery
What is pituitary apoplexy? Describe its onset.
Similar to Sheehan’s syndrome but isn’t specific to women
It is caused by intra-pituitary infarction or haemorrhage (in an already pre-existing adenoma (common)
This also has a RAPID presentation
What are the symptoms of pituitary apoplexy?
- visual defect field (compressed optic chiasm) - BITEMPORAL HERMIANOPIA
- severe, sudden onset headache
How can you test a person to check that their producing a hormone at a normal level?
STIMULATION/PROVOCATION TEST - administration of various releasing hormones
Why is a single measurement of most hypothalamic hormones not useful?
Most hypothalamic hormones tend to be released in pulses
How are the releasing hormones administered in stimulation/provocation tests?
intravenously
Specifically, how are each of the anterior pituitary hormones stimulated and measure in a stimulation/provocation test?
ACTH + GH - ‘street hormones’ —–> (make the person hypoglycaemic) inject insulin and measure cortisol and GH
TSH —–> give TRH and measure TSH
FSH/LH —–> give GnRH and measure FSH/LH
(if you want to have a lot at the pituitary, you can do a pituitary MRI)
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
- 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 E2 plus progestagen To check - Symptom improvement, withdrawal bleeds d. Men – LH/FSH Give testosterone Monitor libido and serum testosterone e. GH Give GH Monitor IGF I
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
Give some causes of short stature
Genetic: - Down’s syndrome - Turner’s syndrome - Prader-Willi syndrome Emotional Deprivation Systemic disease - Cystic Fibrosis - Rheumatoid arthritis Malnutrition Malabsorption - Coeliac disease Endocrine Disorders - Cushing’s syndrome - Hypothyroidism - GH deficiency - poorly controlled T1DM Skeletal dysplasias - Achondroplasia - osteogenesis imperfecta
Describe the growth axis
- hypothalamus stimulates the release of GHRH (and inhibitory somatostatin)
- GH is released from the anterior pituitary
- GH acts as a hormone, but also stimulates the liver to produce IGF I, which mediates growth effects
Briefly describe the causes of short stature in children
Prader-Willi syndrome
Pituitary dwarfism
Laron Dwarfism
How does Prader-Willi syndrome lead to short stature in children?
GH deficiency secondary to hypothalamic dysfunction
(defects are from the hypothalamus)
(tertiary hypopituitarism)
How does pituitary dwarfism syndrome lead to short stature in children?
defects are from the anterior pituitary
secondary hypopituitarism
How does baron dwarfism lead to short stature in children?
How can this be treated?
Mutation in GH receptor - GH receptor defect
Short stature because because IGF I levels are low (because somatotrophin isn’t having its effect)
IGF-1 treatment in childhood can increase height
How is short statues diagnosed in children?
using the mid-parental height
- a predicted adult height is produced based on the average of the mothers and fathers height
- it is important to follow the progression of height across the centiles - a drop of more than 2 centiles is flagged
What are the causes of acquired GH deficiency in adults?
TRAUMA
PITUITARY TUMOUR
PITUITARY SURGERY
CRANIAL RADIOTHERAPY
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
Plasma GH is measured at specific time-points (before and after)
State three alternative triggers to increase GH release to insulin-induced hypoglycaemia in the provocation test?
Arginine
Glucagon
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
How is GH deficiency diagnosed in adults?
Lack of response to GH stimulation test (e.g. insulin-induced hypoglycaemia)
Low plasma IGF I
Low plasma IGF-BP3
What is given in GH therapy and how is it administered?
Preparation:
Human recombinant GH (SOMATOTROPIN)
Administration:
Daily, subcutaneous injection
Monitor clinical response & adjust dose to IGF-1
What are the signs and symptoms of GH deficiency in adults?
- Reduced lean mass, increased adiposity, increased waist:hip ratio
- Reduced muscle strength & bulk -> reduced exercise performance
- Decreased plasma HDL-cholesterol & raised LDL-cholesterol
- Impaired ‘psychological well being’ and reduced quality of life
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 susceptibility to cancer (no evidence)
- Expensive
- Increased risk of cardiovascular accidents
- Increased growth of soft tissue e.g. cardiomegaly
which adenohypophyisis hormones are ‘stress’ hormones?
growth hormones and ACTH
