hyposecretion of anterior pituitary hormones Flashcards
what are the anterior pituitary hormones
FSH LH TSH GH ACTH - tell adrenal cortex to make cortisol prolactin
describe the hypothalamo-pituitary axis
hypothalamus is at the top of the control chain - secretes releasing or inhibiting hormones these cause the ant pit to produce anterior pituitary hormones these act on the endocrine gland causing it to release the primary hormone
list the hormones in the hypathalamo-pituitary-thyroid axis
TRH TSH T3 T4
what type of disease are endocrine system susceptible
autoimmune eg T1DM
what does a ‘primary endocrine gland disease’ refer to *
disorder with the endocrine gland itself - there would be high pituitary hormones but low primary hormones
what does a ‘secondary endocrine disease’ refer to *
problem with the anterior pit - so there are no anterior pituitary hormones and so no signal to the endocrine gland so it doesn’t produce primary hormones
define the term panhypopituitarism *
decreased production of all anterior pituitary hormones
what are the causes of panhypopituitarism *
congenital - rare, mutation of transcription factor genes needed for ant pit development eg PROP1 mutation acquired
what happens if you have congenital panhypopituitarism *
deficient in GH and at least 1 other ant pit hormone short stature - because of GH deficiency hypoplastic anterior pit on MRI - tiny - not developed properly
how can panhypopituitarism be acquired *
tumour - hypothalamic eg craniopharyngiomas - squash ant pit or stop hyp producing releasing hormones OR pituitary - adenomas, metastasis, cysts (squash)
radiation (hypothalamic or pituitary damage) - late effects of cancer treatment, GH most vul, TSH relatively resistant
infection - meningitis
trauma
infiltrative disease - involves the pit stalk - neurosarcoidosis
inflammatory - autoimmune of the ant pit eg hypophysitis
pituitary apoplexy from haemorrhage/ infarction - less common
peri-partum infaction - Sheehan’s syndrome
alternative name for panhypopituitarism
Simmond’s syndrome
presentation of panhypopituitarism - symptoms *
depends on the deficient hormones
FSH/LH - reduced libido, secondary amenorrhoea, erectile dysfunction
ACTH - cortisol deficiency = fatigue
TSH - fatigue
waxy skin, loss of body hair, hypotension
what are the conditions called with deficiency of - FSH/LH - ACTH - TSH *
secondary hypogonadism secondary hypoadrenalism secondary hypothyroidism
describe Sheehan’s syndrome - peri-partum infarction *
cause of hypopituitarism secondary to hypotension which was caused by post-partum haemorrhage because prolactin production increases in pregnancy there is lactotroph hyperplasia there is only a small blood supply via the stalk of the pituitary - so with the hyperplasia there is already a large demand
if there is post partum haemorrhage - the blood vol reduces causing vasoconstrcitor spasm of the arteries- meaning the BP reduces - less blood flows to the ant pit = pituitary infarction
what is the presentation of Sheehan’s syndrome *
lethargy, weight loss and anorexia - because of TSH, ACTH and GH deficiency
failure to lactate - prolactin deficiency
failure to resume menses after birth - FSH/LSH deficiency
difficult to detect this because these symptoms are normal after pregnancy.
describe pituitary apoplexy *
intra-pituitary haemorrhage or infarction dramatic first presentation of benign adenomas (10% pop have them) they can enlarge and haemorrhage can be precipitated by anticoagulants - cause the adenoma to bleed into the pituitary gland
cause sudden onset headache, reduction in visual acuity and/diplopia
why does a pituitary adenoma cause a severe headache *
it stretches the dura
how would you diagnose hypopituitarism biochemically
basal plasma conc of pituitary or target hormones - interpretation limited because hormone levels fluctuate - cortisol v low at night, FSH/LH cyclical, GH/ACTH - pulsatile, T4 t1/2 = 6 days - so level would very on the day
OR stimulated ‘dynamic’ pituitary function tests - ACTH and GH are stress hormones - go up in times of stress, so do insulin induced hypoglycaemia (glucose <2.2mM) - stim GH release, ACTH release (measure cortisol). at same time give TRH and GnRH to get TSH and FSH LH
how can you diagnose hypopituitarism radiologically
pit MRI may reveal - apoplexy, adenoma or an empty sella - thin rim of pituitary tissue (pit gland sits in the sella turcica)
image showing empty sella
how do you treat deficient ACTH *
replace hydrocortisone, given throughout day - lot in morning to mimic the biologic cycle - can never do this perfectly so never have 100% QOL not ACTH because it is spikey, pulsatile check serum cortisol
how do you treat deficient TSH *
give thyroxine check serum free T4 - this is then converted to T3 by deiodination enzymes
how do you treat deficient LH/FSH in men *
give testosterone as a patch or gel or injection check for symptom improvement and serum testosterone
how do you treat deficient LH/FSH in women *
HRT - oestrogen plus progesterone - need both so that they bleed every month because they have an intact uterus otherwise they would get endometrial cancer check -symptom improvement and withdrawal bleeds
how do you treat deficient GH *
replace GH - daily subcutaneous injection check IGF1 and growth chart in children
what does GH deficiency cause *
children- short stature adult - effects less clear
non-endocrine causes of short stature *
genetic - Down’s, Turner’s, Prader Willi
emotional deprivation - childhood trauma shut down stress axis
systemic disease - CF, rheumatoid arthritis
malnutrition
malabsorption - coeliac disease
skeletal dysplasias - achondroplasia, osteogenesis imperfecta
what primary hormones does the liver produce
IGF1 IGFII - mainly embryonic
how does prader willi syndrome affect stature *
effects hypothalamus of axis GHRH -> nothing to stimulate GH also have learning difficulty and food seeking behaviours
how does pituitary dwarfism cause short stature *
not enough GH - problem with anterior pit childhood GH deficiency
how does laron dwarfism cause short stature *
GH receptor defect on liver - don’t make IGF1 - growth need IGF1 and GH IGF1 treatment in childhood can increase height
describe dwarfism from achondroplasia *
mutation in fibroblast growth factor 3 abnormality in the growth plate chondrocytes - impaired linear growth average size trunk short arms and legs
endocrine causes of short stature *
cushings hypothyroidism GH deficiency - pituitary dwarfism poorly controlled T1DM
describe the diagnosis of short stature *
look at the height centiles the child is 2SDs less than mean height for children of that age and sex or they drop off their trajectory
graph of centiles for a person of low stature, but was treated at 11
describe the diagnosis of GH deficiency *
random GH - not useful - pulsatile
instead use provocative challenge ie stimulation test: give GHRH, arginine (AA stimulate GH production), insulin (force hypoglycaemia), glucagon - stimulate ACTH and GH causes vomiting which causes the stress response, exercise - more in children
measure GH over time it should increase in normal people if does not raise above 3mcg/L - NICE cut off - allowed hormone therapy - expensive
describe GH therapy *
prep - human recombinant GH - somatotrophin admin - daily subcutaneous injection, monitor clinical dose and adjust to IGF1
GH deficiency in adults signs and symptoms
reduced lean mass, increased adiposity, increased waist:hips ratio
relaxed muscle strength and bulk - reduced exercise performance
decreased plasma HDL cholesterol and high LDL cholesterol
impaired physiological well being and reduced QOL - don’t feel well in self
potential benefits of GH therapy in adults *
improved body composition, decreased waist circumference, less visceral fat - good for CV health
improved muscle strength and exercise capacity more favourable lipid profile - higher HDL, less LDL
increased bone mineral density
improved physiological well being and QOL
potential risks of GH therapy in adults *
expensive increased susceptibility to cancer - no data to support this
treatment of panhypopituitarism *
hormone replacement therapy as required
