pituitary Flashcards
growth hormone deficiency: list the endocrine and non-endocrine causes of short stature, explain how a diagnosis of endocrine short stature is made, recall the pharmacodynamic and pharmacokinetic properties of human growth hormone and the rationale governing its use
replacement and check if GH deficient
GH; IGF1, growth chart (children)
other name of growth hormone
somatotrophin
effect of GH deficiency in children
short stature (2 s.ds < mean height for that age and sex); can give GH if proved deficient
7 categories of short stature causes
genetic, emotional deprivation (stress axis), systemic disease, malnutrition, malabsorption, endocrine disorders, skeletal dysplasias
3 genetic causes of short stature
Down’s syndrome, Turner’s syndrome, Prader Willi syndrome
2 systemic diseases causing short stature
cystic fibrosis, rheumatoid arthritis
malabsorption cause of short stature
coeliac disease
4 endocrine diseases causing short stature
Cushing’s syndrome (excess cortisol), hypothyroidism, GH deficiency, poorly controlled type 1 diabetes mellitus
2 skeletal dysplasias causing short stature
achondroplasia, osteogenesis imperfecta
growth axis of somatotrophin
hypothalamus -> GHRH (inhibited by somatostatin) -> adenohyphysis -> somatotrophin -> direct: target tissues; indirect: liver -> release of IGFI (and IGFII) -> target tissues
growth axis: where does Prader Willi syndrome affect
hypothalamus, so GHRH and consequently GH deficiency; secondary to hypothalamic dysfunction
growth axis: cause of short stature due to pituitary dwarfism
lack of somatotrophin released
growth axis: cause of Laron dwarfism
GH receptor defect in liver
dwarfism: achondroplasia: mutation
mutation in fibroblast growth factor receptor 3 (FGF3)
dwarfism: achondroplasia: what causes impaired linear growth
abnormality in growth plate chondrocytes so skeletal issue
dwarfism: achondroplasia: clinical presentation
average trunk size, short limbs
dwarfism: pituitary
childhood GH deficiency
dwarfism: Laron dwarfism: mutation and treatment
mutation in GH receptor; treated with IGF1 in childhood to increase height
diagnosis of short stature: mid-parental height
predicted adult height based on father’s and mother’s height
diagnosis of short stature: monitoring height
drop of more than 2 centiles is flagged and investigated (e.g. coeliac disease so gluten-free diet then continues to grow at normal rate)
4 causes of acquired GH deficiency in adults, and what they affect
trauma, pituitary tumour, pituitary surgery, cranial radiotherapy; all affect region before reaching liver or target tissues (secondary disease)
how is GH deficiency diagnosed in adults
as GH is pulsatile, random GH test is of little use; instead, provocative challenge (stimulation test)
GH provocation tests: 4 factors and measurement
GHRH and arginine (may inhibit somatostatin release) injected (i.v.), insulin (promote hypoglycaemia) injected (i.v.), glucagon (causes secretion of ACTH and GH as causes vomiting, causing stress) injected (i.m.), exercise (e.g. 10 min step climbing when appropriate); measure plasma GH at specific points before and after
GH secretion in response to hypoglycaemia (insulin tolerance test)
normally increases hugely upon IV insulin injection (above NICE cut-off of 3mcg/L), but if GH deficient then won’t reach cut-off so warrant treatment
GH therapy preparation
human recombinant GH (somatotropin); not usually required in adults as finished growing
GH therapy administration
daily, subcutaneous injection; monitor clinical response and adjust dose to IGF1
4 signs and symptoms of GH deficiency in adults
reduced lean mass (increased adiposity and waist:hip ratio), reduced muscle strength and bulk (reduced exercise performance), decreased plasma HDL-cholesterol and raised LDL-cholesterol, impaired psychological well-being and reduced quality of life
5 potential benefits of GH therapy in adults
improved body composition (reduced waist:hip ratio and less visceral fat), improved muscle strength, more favourable lipid profile (increased plasma HDL-cholesterol and decreased LDL-cholesterol), increased bone mineral density, improved psychological well-being and quality of life
2 potential risks of GH therapy in adults
possibly increased susceptibility to cancer (helps cells to grow), expensive lifelong treatment
what type of hormone is growth hormone
polypeptide (protein)
are protein hormones absorbed well when given orally
no
duration of action of protein vs steroid hormones
steroid hormones are longer acting (>24hrs)
where do protein hormones act on
membrane-bound receptors
