Hyposecretion of Anterior Pituitary Hormones Flashcards
List the 5 anterior pituitary hormones
- FSH / LH
- Prolactin
- GH
- TSH
- ACTH
1) What is a primary endocrine gland disease?
2) What is a secondary endocrine gland disease?
3) What is a tertiary endocrine gland disease?
1)
- A disorder in the endocrine glands themselves (gonads, thyroid, adrenal cortex etc) which secrete primary hormones
2)
- A disorder in the anterior pituitary which secrete anterior pituitary hormones
3)
- A disorder in the hypothalamus which secrete releasing / inhibitory hormones to the pituitary
Define panhypopituitarism
‘Decreased production of ALL anterior pituitary hormones’
Define hypopituitarism
‘Decreased production of all (panhypopituitarism) or specific pituitary hormones’
1) What is the basic principle for congenital panhypopituitarism?
2) Give a specific example of a particular pathopsyiological cause of congenital panhypopituitarism
1)
- Mutated gene for transcription factor necessary for normal AP development
2) Mutated PROP1 gene
What hormones are deficient in congenital panhypopituitarism and what sign does it always cause at the very least?
- Deficient in GH and at least one more
- So short stature always
How is congenital panhypopituitarism visualised diagnostically - imaging?
- Pituitary MRI
- Hypoplastic pituitary seen
What is Simmond’s disease?
Another name for panhypopituitarism
What symptoms are there in the presentation of panhypopituitarism based on the hormones involved - include the name of the disorder along the name of the disorder along each hormone where possible?
- FSH / LH deficiency - secondary hypogonadism
- Reduced libido
- Secondary amenorrhoea (women)
- Erectile dysfunction (men)
- ACTH (thus cortisol) deficiency - secondary hypoadrenalism
* Fatigue - TSH - secondary hypothyroidism
* Fatigue
List the 9 causes of acquired panhypopituitarism and give more detail if necessary
- Pituitary apoplexy
- Sheehan’s syndrome
- Infection e.g. meningitis
- Inflammation (hypophysitis)
- Infiltrative disease e.g. neurosarcoidosis
- Trauma
- Pituitary tumour - craniopharyngiomas
- Pituitary surgery
- Radiation
1) Describe the pathophysiology of Sheehan’s syndrome
2) How might Sheehan’s syndrome present?
1)
- Post-partum haemorrhage causes hypotension AND
- Lactotroph hyperplasia increases blood demand to pituitary
- Both the lack of supply and high demand cause pituitary infarction and therefore post-partum hypopituitarism
2)
- TSH + ACTH + GH deficiency → lethargy, anorexia, weight loss
- PRL deficeincy → failure of lactation
- FSH / LH deficiency → failure to resume menses post-delivery
1) What is the pathophysiology of pituitary apoplexy?
2) What might precipitate pituitary apoplexy?
3) What are the visual field defects associated with pituitary apoplexy and explain why these occur?
1) Pituitary haemorrhage / infarction
2) Anticoagulants
3)
- All arise due to the structures within the cavernous sinus (of which the pituitary is one of the contained structures)
- Bitemporal hemianopia due to compressed optic chiasm
- Ptosis (droopy eyelids) - due to compressed oculomotor nerve so impaired levator palpebrae superioris
- Diploplia (double vision - crossed eyes) - due to compressed trochlear and abducens nerves so impaired superior oblique and lateral rectus respectively
Give 4 reasons that basal plasma concentrations of pituitary or target endocrine gland hormones is a poor technique for diagnosing hypopituitarism
- ACTH / cortisol - diurnal rhythm so difficult
- FSH / LH - cyclical so difficult
- GH / ACTH - pulsatile so difficult
- T4 half-life is high (6 days) so if you measure too close to before onset of pathology, you might get a false negative due to remaining high T4
Methods of using stimulated ‘dynamic’ pituitary function tests for function of hypopituitarism diagnostic measurement of…
1) GH / ACTH?
2) TSH?
3) FSH / LH?
1)
- Insulin induced hypoglycaemia - there should be an increase in GH / ACTH (thus cortisol) in a homeostatic response to maintain blood sugar levels
- N.B. use [cortisol] as a surrogate measure of [ACTH] because ACTH rapidly degrades
- If there is no spike in the levels of GH / cortisol - these are deficient
2)
- Administer TRH → should stimulate TSH release → measure [TSH] - if its low and doesn’t increase in response, then this is deficient
3)
- Administer GnRH → should stimulate FSH / LH secretion → measure [FSH / LH] - if its low and doesn’t increase in response, then this is deficient
Discuss the use of radiological diagnosis to diagnose hypopituitarism and what you might see
- Empty sella turcica
- Hypoplastic pituitary
- May also reveal underlying pathology e.g. haemorrhage or pituitary adenoma
Outline for each anterior pituitary hormone, what therapy you would give in case of deficiency and how you would check progress to see if they are still deficient:
1) ACTH
2) TSH
3) FSH / LH (women)
4) FSH / LH (men)
5) GH
1)
- Hydrocortisone / fludrocortisone
- Check serum cortisol
2)
- Thyroxine replacement therapy
- Check free T4 levels
3)
- E2 + Progestagen
- Check symptoms and check for withdrawal bleeds
4)
- Testosterone replacement therapy
- Check symptoms and serum testosterone
5)
- GH therapy
- Check growth chart in children or check IGF-1 levels
Why can you not give E2 alone in HRT for women deficient in FSH / LH?
- Because E2 unopposed by progesterone (given using progestagen) can lead to endometrial hyperplasia
Outline the complete growth axis
- Hypothalamus secretes both GHRH and SS (somatostatin) which are releasing and inhibiting factors for GH respectively
- Anterior pituitary somatotrophs secretes GH
- GH either directly binds receptors on target tissue to exert its effect or binds receptors on the liver
- Liver secretes IGF-1 and IGF-II in response to binding of GH on its GH receptors
- IGF-I and IGF-II both also act on target tissues to exert their effects
List 5 pathological causes of short stature
- Achondroplastic dwarfism
- Prader-Willi syndrome
- Pituitary dwarfism
- Laron dwarfism
- Pygmy dwarfism
1) How does Prader-Willi syndrome cause short stature?
2) How to treat the short stature in PWS?
1)
- GH deficiency secondary to hypothalamic dysfunction (tertiary endocrine disease)
2)
- GH therapy
1) How does achondroplastic dwarfism cause short stature?
2) What does achondroplastic dwarfism look like?
1)
- Mutation in FGF23 gene
- Defective growth plate chondrocytes
- Impaired linear growth
2)
- Short limbs
- Normal sized trunk
How does pituitary dwarfism cause short stature?
How to treat pituitary dwarfism?
1)
- Lack of GH
2)
- GH therapy
1) How does Laron dwarfism cause short stature?
2) How to treat Laron dwarfism?
1)
- It is a defect in the GH receptors in the liver
- Therefore less IGF-1 and IGF-II is secreted
2)
- IGF-1 replacement therapy
How to monitor height in children, and when would you get suspicious of a pathology causing short stature?
- Use growth charts which measure growth in centiles
- They should grow steadily along their centile line or higher, if they drop more than 2 centiles, this is flagged for potential pathology
List 4 causes of acquired GH deficiency
- Trauma
- Pituitary tumour
- Pituitary surgery
- Cranial radiotherapy
Describe the 4 types of GH provocation tests, giving more detail when needed - i.e. what stimulates GH release and can be used in these provocation tests?
- Insulin-induced hypoglycaemia - causes homeostatic response with increased GH
- GHRH + Arginine - note arginine inhibits SS
- Glucagon (i.m.)
- Exercise
How is GH therapy administered?
- Daily
- Subcutaneous injection
What does a low GH cause - what signs / symptoms apart from obviously short stature?
- Increase adiposity / waist-hip ratio
- Poor lipid profile - decrease in plasma HDL cholesterol and increase in plasma LDL cholesterol
- Poor bone mineral density
- Impaired psychological well-being and reduced quality of life
Apart from resolving short stature in some cases, what other benefits may there be to GH therapy?
- Improved body composition - less adiposity and lower waist-hip ratio
- Increased muscle strength and exercise capacity
- Better lipid profile - increases HDL cholesterol and lowers LDL cholesterol
- Increases bone mineral density
- Improves psychological well-being and quality of life
Give 2 negatives to GH therapy
- Increased susceptibility to cancer
- Expensive
How does Pygmy dwarfism cause short stature?
- IGF-1 receptor defect
