1. Hyposecretion of anterior pituitary hormones Flashcards
what is another name for the anterior pituitary and posterior pituitary?
anterior - adenohypophysis
posterior - neurohypophysis
list the anterior pituitary hormones
FSH/LH prolactin GH TSH ACTH
what is primary hypothyroidism?
disorder resulting in primary endocrine gland disease
what is secondary hypothyroidism?
dysfunction to the signal going to the endocrine gland
what is panhypopituitarism?
decreased production of all the anterior pituitary hormones
what is congenital panhypopituitarism?
rare, usually due to mutations of transcription factor genes needed for anterior pituitary development (e.g. PROP1 mutation)
deficient in GH and at least 1 more anterior pituitary hormone
what is acquired panhypopituitarism caused by?
- tumours: hypothalamic or pituitary (adenomas, metastases, cysts)
- radiation: GH is most vulnerable, TSH is relatively resistant
- infection: e.g. meningitis
- traumatic brain injury
- infiltrative disease: e.g. neurosarcoidosis
- inflammatory disease
- pituitary apoplexy: haemorrhage
- peri-partum infarction: Sheehan’s syndrome
what is panhypopituitarism occasionally called?
Simmond’s disease
what is secondary hypogonadism and what does it lead to?
loss of FSH/LH
- reduced libido
- secondary amenorrhoea (female)
- erectile dysfunction (male)
what is secondary hypoadrenalism and what does it lead to?
no ACTH -> no cortisol
- fatigue
what is secondary hypothyroidism a loss of and what does it lead to?
loss of TSH
- fatigue and weight gain
what is Sheehan’s syndrome?
post partum hypopituitarism:
- anterior pituitary enlarges in late stages of pregnancy
- lactotroph hyperplasia to produce prolactin as the body prepares to breast feed
- enormous loss of blood during post partum haemorrhage and BP drops (hypotension) -> pituitary receives insufficient blood supply
what does post partum haemorrhage ultimately result in?
pituitary infarction -> irreversible damage
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 not usually affected
what is pituitary apoplexy and in whom does it usually present?
intra-pituitary haemorrhage/ infarction
dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
what do patients with pituitary apoplexy present with?
- severe, sudden onset headache
- visual field defect because the haemorrhage compresses the optic chiasm -> bitemporal hemianopia
- involvement of the cavernous sinus may lead to cranial nerve damage (diplopia, ptosis)
why are cortisol, T4 and FSH/LH not a good measure of pituitary function?
cortisol - pulsatile
T4 - long half life (6 days) so might not have cleared from previous release
FSH/LH - cyclical
what is a good measure of pituitary function?
GH release/ACTH release (cortisol measured) when stress is induced by insulin-induced hypoglycaemia
TRH may be given to stimulate TSH release
GnRH may be given to stimulate FSH/LH release
how can ACTH be replaced and how can it be checked?
hydrocortisone
check serum cortisol
how can TSH be replaced and how can it be checked?
thyroxine
check serum free T4
how can LH/FSH in women be replaced and how can it be checked?
HRT (E2 + progestogen)
check symptom improvement, withdrawal bleeds
oestrogen can be given in women up to age 50 (estimated menopause). you cannot give unopposed oestrogen with an intact uterus due to risk of endometrial cancer, it must be given with progestogens
how can LH/FSH in men be replaced and how can it be checked?
testosterone
symptom improvement, serum testosterone
how can GH be replaced and how can it be checked?
GH
IGF1, growth chart (children)
which hormone cannot be replaced?
prolactin
what are the causes of short stature?
- genetic: down’s syndrome, turner’s syndrome, prader willi syndrome
- emotional deprivation due to negative effects of stress on growth axis
- systemic disease: cystic fibrosis
- malnutrition
- malabsorption: coeliac disease
- endocrine disorders: cushing’s syndrome, hypothyroidism
- skeletal dysplasias
which 2 hormones regulate growth in the hypothalamus?
- growth hormone releasing hormone (dominant)
2. somatostatin (less impactful)
what does somatotrophin produced in the anterior pituitary do?
travel to the liver to produce somatomedins: IGF1, IGF2
how does prader willi syndrome cause short stature?
GH deficiency due to hypothalamic dysfunction (no GHRH produced)
how does dwarfism cause short stature?
achondroplasia -> skeletal problem
mutation in fibroblast growth factor receptor 3 resulting in abnormality in growth plate chondrocytes (impaired linear growth)
normal trunk but shortened limbs
how does pituitary dwarfism cause short stature?
lack of GH
how does laron dwarfism cause short stature?
receptor abnormalities (mutation in GH receptors) so GH produces no biological effect
IGF-1 treatment in childhood can increase height
what are the causes of acquired GH deficiency in adults?
- trauma
- pituitary tumour
- pituitary surgery
- cranial radiotherapy
how is GH deficiency diagnosed?
stimulation test
this is because GH release is pulsatile so sample taking has little use
give examples of GH provocation tests
- GHRH + arginine
- insulin tolerance test: make patient hypoglycaemic and measure GH response
- give glucagon: makes patient vomit which induces stress
- exercise
what is GH secretion in response to hypoglycaemia in a normal person and a GH deficient person?
- lots of GH made in a normal person’s response
- little-no response in GH deficient person
what does growth hormone therapy consist of?
subcutaneous peptide injection of human recombinant GH (somatotropin) administered daily
monitor clinical response and adjust dose to IGF1
what are the signs of symptoms of GH deficiency in adults?
- reduced lean mass, increased waist:hip ratio due to more central fat
- reduced muscle strength and bulk
- decreased plasma HDL-cholesterol and raised LDL-cholesterol (can lead to CVD)
- impaired physiological wellbeing and reduced quality of life
what are the potential benefits of GH therapy in adults?
- improved body composition
- improved muscle strength and exercise capacity
- more favourable lipid profile
- increased bone mineral density
- improved psychological wellbeing and quality of life
what are the potential risks of GH therapy in adults?
- increased susceptibility to cancer
- expensive: lifelong GH treatment = £42,000
