Hyposecretion of ant. pit hormones Flashcards
what are the adenohypophyseal hormones?
FSH/LH prolactin GH TSH ACTH
what is a primary endocrine disease?
a disease that affects the endocrine gland itself e.g. thyroid
what is the state of decreased production of all adenohypophyseal hormones?
hypopituitarism
can be congenital (rare) or acquired
- Simmonds disease
what causes congenital hypopituitarism?
mutations in transcription factor genes for normal pit development i.e. PROP1 mutation
what is the outcome of such mutations like PROP1 in hypopituitarism?
deficiency in growth hormone and at least one other pituitary hormone
what is a cardinal sign of hypopituitarism
short stature
sign of hypopituitarism on MRI investigation
hypoplastic adenohypophysis on MRI
what are the different causes of the more common acquired hypopituitarism?
- tumours
- radiation
- infection e.g. meningitis
- traumatic brain injury
- infiltrative disease e.g. neurosarcoidosis
- pituitary apoplexy (resulting from haemorrhage)
- peri-partum infarction (Sheehans syndrome)
what are the types of tumours in acquired hypo/panhypopituitarism?
hypothalamic- craniopharyngioma
pituitary- adenoma, metastases, cysts
how does radiation cause hypopituitarism?
hypothalamic or pituitary damage
GH is most vulnerable while TSH can be relatively resistant
what is hypopituitarism sometimes called?
Simmonds Disease
what hormones are mostly affected by hypopituitarism?
FSH/LH
ACTH
TSH
how does an FSH/LH deficiency present itself?
secondary hypogonadism
- reduced libido
- secondary amenorrhoea
- erectile dysfunction
what is a secondary endocrine disease?
disease that affects the signalling process at the pituitary impacting the signal to the endocrine gland further down the line
how does a ACTH deficiency present itself?
secondary hypoadrenalism
- fatigue
how does TSH deficiency present itself?
secondary hypothyroidism
- fatigue
- weight gain
- LOW TSH, low T3/T4 due to issue in the pituitary
what is Sheehan’s syndrome?
- specific to post-partum hypopituitarism
- commonly due to haemorrhage
- presents secondary to hypotension
- less common in developed countries
what causes Sheehan’s syndrome?
ischaemic necrosis of the pituitary
in normal pregnancy, the anterior pituitary lactotrophs enlarge to produce prolactin
the hypotension from loss of blood when giving birth causes the pituitary to become under-perfused and then infarcts
what are the noticeable and hard to notice presentations of Sheehan’s?
hard- lethargy, anorexia, weight loss (due to pit hormone deficiencies)
easy- failure to lactate (prolactin deficiency), failure to resume normal menstruation cycle post-delivery
what is pituitary apoplexy?
- due to intra-pit haemorrhage (or infarction)
- has a dramatic presentation in those with a pre-existing pit adenoma (regardless of whether it was known of)
- precipitated by anti-coagulants
what are the symptoms of pituitary apoplexy?
- severe sudden onset headache
- bilateral hemianopia
- diplopia (CN 4 and 6)
- ptosis (CN 3)
why is it difficult diagnosing hypopituitarism?
hormones like cortisol fluctuate during the day, Gh is pulsatile, LH/FSH are cyclic, T4 has a half life of 6 days
how is hypopituitarism biochemically diagnosed?
- basal plasma concentrations of hormones
- stimulated pituitary function tests
what is involved in the stimulated pituitary function tests?
- triggering the ‘stress’ hormones ACTH and GH under stress (hypoglycaemia )
- an insulin induced hypoglycaemia stimulates GH and ACTH release
- injected TRH stimulates TSH release and GnRH stimulates FSH and LH
what is seen on the MRI in hypopituitarism?
pituitary MRI
can reveal the ‘empty sella’
a thin rim of pituitary tissue
what is the definition of short stature in children and adults?
children= >2SDs from the mean for their age and sex
adults= less clear
what are the different causes of growth hormone deficiency?
- genetic e.g. Prader-Wili, Downs, Turners
- emotional deprivation
- systemic disease
- malnutrition
- malabsorption e.g. coeliac disease
- endocrine disorders e.g. Cushing’s, GH def
- skeletal dysplasia e.g. osteogenesis imperfecta
what are the causes of dwarfism?
achondroplasia
- mutation of in FGFR3 (fibroblast growth factor receptor 3)
- abnormalities in growth plate chondrocytes leads to impaired growth –> short arms/legs
what is pituitary dwarfism?
childhood GH deficiency
how does Prader Wili syndrome present?
GH deficiency secondary to hypothalamic dysfunction
what causes Laron dwarfism?
mutation in GH receptor in childhood
what are the causes of acquired GH deficiency in adults?
- trauma
- pituitary tumour/surgery
- cranial radiotherapy
how is acquired GH deficiency diagnosed?
provocative challenge - as GH is pulsatile, it is hard to measure - tests include: GHRH + arginine (IV) insulin IV glucagon IV exercise
plasma GH is measured at specific time points
what is the NICE cut off to determine GH deficiency?
<3mcg/L
what is involved in Growth Hormone Therapy?
- preparation: human recombinant GH
- administation: daily subcutaneous injection, monitor response and adjust dose to IGF-1
- Absorption & distribution – maximal concentration in plasma in 2-6 hours.
- Metabolism – hepatic/renal with a short half-life of 20 minutes.
- duration of action – lasts well beyond clearance, peak IGF1 levels at approx. 20 hours.
what are the symptoms of GH deficiency?
- reduce lean mass
- reduced muscle strength/bulk
- decreased plasma HDL
- impaired psychological well-being
- increased adiposity
- reduced exercise performance
- raised LDL
- increased waist: hip ratio
GHRT helps reverse these effects
what are the risks of GHRT?
- increased susceptibility to cancer
- expensive
what is the defect in Pygmy dwarfism?
IGF1 receptor defect
