Hyposecretion of Anterior Pituitary Hormones Flashcards
What are three main types of panhypopituitarism?
Simmond’s Disease
Sheehan’s Syndrome
Pituitary Apoplexy
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
Can be congenital or acquired
What are the features of congenital panhypopituitarism?
- Rare
- CAUSE: Usually due to mutations of transcription factor genes needed for normal anterior pituitary development eg PROP1 mutation
- Deficient in GH and at least 1 more anterior pituitary hormone
Presentation:
- Short stature
- Hypoplastic anterior pituitary gland on MRI
List some different types of acquired panhypopituitarism.
- Tumours- hypothalamic-craniopharyngioma; pituitary–adenomas, metastases, cysts.
- Radiation- hypothalamic/pituitary damage, GH most vulnerable, TSH relatively resistant
- Infection eg meningitis
- Traumatic brain injury
- Infiltrative disease – often involves pituitary stalk eg neurosarcoidosis
- Inflammatory (hypophysitis) - pituitary is recognised as non-self
- Pituitary apoplexy - haemorrhage (or less commonly infarction)
- Peri-partum infarction (Sheehan’s syndrome)
Describe the presentation of Simmond’s disease (panhypopituitarism) .
Symptoms due to deficient hormones:
FSH/LH:
- Secondary hypogonadism
- Reduced libido
- Secondary amenorrhoea
- Erectile dysfunction
ACTH:
- Secondary hypoadrenalism (cortisol deficiency)
- Fatigue
TSH:
- Secondary hypothyroidism
- Fatigue
State the cause of Sheehan’s syndrome and describe its onset.
This is specific to WOMEN
Anterior pituitary enlarges during pregnancy (lactotroph hyperplasia)
Sheehan’s = vasoconstrictor spasm of hypophysial arteries as a result of post-partum haemorrhage (hypotension after haemorrhage) –> large pituitary no longer gets enough blood supply so cannot function proper –> spasm causes pituitary infarction
This develops very RAPIDLY
Why does the anterior pituitary enlarge during pregnancy?
Lactotroph hyperplasia
How does Sheehan’s syndrome present?
- Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
- Failure of lactation – PRL deficiency
- Failure to resume menses post-delivery
Posterior pituitary usually not affected
What is pituitary apoplexy? Describe its onset and which patients it most affects.
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 in patients with:
- pre-existing pituitary tumours
- or may be the first presentation of a pituitary adenoma.
- or can be precipitated by anticoagulants.
Describe the onset/presentation of pituitary apoplexy.
SEVERE sudden onset headache - “apopletic rage”
Visual field defect – compressed optic chiasm, bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia(double vision) (CNIV, VI), ptosis (drooping of upper eyelid)(CNIII)
Why is a single measurement of most hypothalamic hormones not useful?
Most hypothalamic hormones tend to be released in pulses
FSH/LH is cyclical
GH/ACTH is pulsatile
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 stimulated pituitary function tests?
Intravenous
Describe how the stimulates pituitary function tests are done.
- ACTH and GH are “stress” hormones = hypoglycaemia <2.2mM = stress so you give insulin to stimulates GH and ACTH(measure cortisol)
- To stimulate TSH give TRH
- To stimulate FSH&LH give GnRH
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 - Monitor libido and oestrogen deficiency
d. Men – LH/FSH - Give testosterone undecanoate - 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) - 2SD<mean></mean>
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State some other causes of short stature.
Genetic
Malnutrition
Emotional deprivation
Endocrine disorders
Skeletal dysplasias
Systemic disease
Malabsorption e.g. coeliac disease
Malnutrition
List some genetic diseases, systemic diseases and skeletal dysplasias which can cause short stature.
Genetic - Down’s syndrome, Turner’s syndrome, Prader Willi syndrome
Systemic disease - Cystic Fibrosis, Rheumatoid arthritis
Skeletal dysplasias - Achondroplasia, osteogenesis imperfecta
What are most common endocrine-related causes of short statue?
- Decreased production of GHRH/deficiency
- Cushing’s syndrome
- Hypothyroidism
- Poorly controlled T1DM
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
List three causes of short stature in children and state where they affect the growth axis.
- Pituitary dwrafism - lack of GH in childhood
- Laron dwarfism - GH receptor defect
- Praeder Willi syndrome - GH deficiency secondary to hypothalamic dysfunction
What is achondroplasia? Is it an endocrine disorder?
- Achondroplasia = mutation in FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGF3)
- Abnormality in growth plate chondrocytes - impaired linear growth
- Average size trunk
- Short arms and legs
What type of dwarfism is caused by a GH receptor defect?
Laron Dwarfism
Describe the IGF I levels in people with Laron dwarfism. What is the treatment?
LOW IGF I
Because functioning GH receptors are necessary for GH to stimulate the production of IGF I
IGF-I treatment in children can increase height
How do you diagnose short stature in children?
Use mid-parental height -predicted adult height based on father’s and mother’s height.
Height is monitored on centile charts and recorded - if the child falls off the centile chart at any point this may be due to a hormone deficiency
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?
PROVACATION CHALLENGE = Insulin-induced hypoglycaemia
Hypoglycaemia is a potent stimulus for growth hormone release
State three other triggers (other than insulin induced hypoglycaemia) for an increase in GH release.
- GHRH + Arginine (more effective in combination)
- 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
Measure plasma GH at specific time points before and after.
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 the human recombinant GH in GH therapy administered, how often and how is it monitored?
- Daily, subcutaneous injection
Monitor clinical response & adjust dose to IGF-1
NB: approved naem = SOMATOTROPIN
State some signs and symptoms of GH deficiency in adults.
- Decreased muscle mass
- Increased adiposity
- Increased waist: hip ratio
- Decreased plasma HDL and increased LDL
- Reduced muscle strength and bulk –> reduced exercise performance
- Impaired psychological wellbeing and 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 - but no data to support this currently
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
In what order does loss of secretion occur?
Usually develops in adults with progressive loss of pituitary secretion
- Gonadotrophins
- GH
- Thyrotrophin
- Corticotrophin
- Prolactin
What is a problem with growth hormone therapy in children?
Tolerance may develop so you need to think about when to start GH therapy
