Endocrinology - Basic Principles Flashcards
what are the 3 types of hormone?
proteins and peptides - insulin, GH, prolactin
steroids - cortisol, testosterone
tyrosine and tryptophan derivatives (amino acids) - adrenaline, thyroid hormones, melatonin
what type of receptor is the insulin receptor?
tyrosine kinase
what are the 4 types of hormone receptor?
tyrosine kinase
nuclear/steroid?
GPCR
steroid/nuclear?) receptor (can be in nucleus or cytoplasm and move to the nucleus)
receptors associated with tyrosine kinase activity
which receptor causes change in transcription?
steroid/nuclear
what are the key features of GPCR?
extracellular domain and intracellular domain
transmembrane (crosses membrane 7 times)
associated G protein (alpha, beta, gamma subunits)
activates regulatory signalling cascades (cAMP, IP3)
give 2 examples of cytokine receptors (linked to tyrosine kinase activity)?
prolactin receptor
growth hormone receptor
- works via same principle as tyrosine kinase
how do steroid/nuclear receptors work?
intracellular - either cytoplasm or nucleus
steroid/receptor complex binds to DNA response elements
results in change in gene transcription
how do glucocorticoid receptors work?
corticosteroids enter the cells and bind to the glucocorticoid receptor (GR) in the cytoplasm and translocate to the nucleus where the transcription of target genes is initiated/inhibited
what hormones are secreted by anterior pituitary?
GH LH/FSH ACTH TSH PRL
what hormones are secreted by the posterior pituitary?
ADH
oxytocin
what is the major determinant of hormone concentration?
rate of secretion
- determined by highly refined feedback loops
when might TSH not be a reliable marker of thyroid status?
in pituitary dysfunction
why shouldn’t you check thyroid function when sick/in hospital?
hormones can be irregular in illness
what tests are done to assess pituitary function?
9am cortisol T3/T4 TSH Prolactin IGF1 LH, FSH, E2/testosterone Us&Es, plasma/urine osmolality imagine MRI synacthen test
what is the synacthen test?
where you give synthetic ACTH and test cortisol response
synACTHen
what is released from the hypothalamus to stimulate the anterior pituitary?
corticotropin releasing hormone (CRH)
gonadrtrophin
TRH
how do you measure cortisol and why?
9am cortisol
circadian/diurinal secretion of cortisol through day so will be at different levels
- random cortisol therefore not useful
how is growth hormone measured?
random measurement is useless
measuring IGF1 can give a good indication of GH hypersecretion
when should sex hormones be measured?
testosterone = at 9am female = depends on timing in menstrual cycle
what is prolactin?
secreted by lactotroph cells of the anterior pituitary
what regulates prolactin secretion?
tonic inhibition by hypothalamic dopamine
secretion regulated by a short-loop negative feedback
effects of prolactin mediated by prolactin receptor
which hormone released from the posterior pituitary regulates thirst and water balance?
vasopressin
V1 causes vasoconstriction
V2 causes fluid reabsorption
what are the principles of dynamic pituitary testing?
biochem tests before imaging (usually)
to test hormone excess = suppression test (e.g dexamethasone suppression test)
if testing if hormone deficiency = stimulation test (e.g synacthen)
imaging then used to localise/characterise disease after biochemical diagnosis
combined biochem/imaging diagnosis might be needed
what can cause a cortisol deficiency?
adrenal insufficiency
- adrenal failure (addisons disease), pituitary disease etc
what can cause cortisol excess?
cushings syndrome
what causes Chushing’s syndrome?
pituitary origin - tumour arising from corticotroph cells in anterior pituitary - most common cause adrenal origin - ACTH independent - adrenal hyperplasia/adenoma/carcinoma ectopic ACTH - malignancy exogenous steroids
what are the features of Cushing’s disease?
acne hirsutism abdominal striae and central obesity interscapular and supraclavicular fat pads proximal myopathy osteoporosis hypertension impaired glucose tolerance cushingoid facies (moon face)
name 2 ACTH dependant and 2 ACTH independent causes of Cushing’s syndrome/
dependant - excess ACTH production in pituitary - ectopic ACTH independent - adrenal problem producing excess cortisol - exogenous steroids
how is cushing’s syndrome diagnosed?
low dose dexamethasone suppression test
- failure to suppress = cushings syndrome diagnosis
other investigations in cushing’s disease?
measure of ACTH
- low ACTH = adrenal origin is likely
- high ACTH = could be cushings disease or ectopic ACTH
high cortisol and ACTH indicates pituitary origin
cushings disease vs syndrome?
disease = pituitary tumour causing the symptoms syndrome = the general term for the symptoms of any cause
what are the 3 screening tests for cushings syndrome?
1mg overnight dexamethasone suppression test
24 urinary free cortisol
midnight cortisol
