Endocrine Principles Flashcards
give examples of tyrosine and tryptopgan derivatives
adrenaline, thyroid hormones, melatonin
what does tyrosine kinase do
adds phosphate to a tyrosine molecule
why do steroid hormone receptors not acts as quickly
as make changes in transcription
name 2 regulatory signalling cascade activated by GPCRs
cAMP, IP3
what is GPCRs main role in endocrinology
sensors on internal environment
what happens if there is a mutation in a GCPR
the hormone that is meant to bind to it will lose it effect
what type of receptor binds to insulin
intrinsic tyrosine kinase receptor (binds to pre formed dimer)
where are steroid hormone receptors usually
intracellular- cytoplasm or nucleus
what do steroid receptor complexes do
bind to DNA response elements, cause changes in gene transcription
name two nuclear steroid receptors
estrogen and androgen receptors
describe the process of e.g. a corticosteroid binding to a glucocorticoid receptor
Corticosteroids enter the cell, bind to the glucocorticoid receptor (GR) in the cytoplasm and translocate to the nucleus, where the transcription of target genes is initiated
Through transactivation, binding of the activated glucocorticoid receptor homodimer to a GRE in the promoter region of steroid-sensitive genes leads to the transcription of genes encoding anti-inflammatory mediators
what is released by the posterior pituitary
ADH, oxytocin
what is released by the anterior pituitary
GH, LH/FSH, ACTH, TSH, PRL
is the anterior/ posterior pituitary more under hypothalamic control
anterior
what is the major determinant of hormone concentration
rate of secretion
what is used to evaluate thyroid hormone
TSH assay
why should you not measure thyroid hormones in the acutely unwell
as get abnormalities (low free hormone levels and low/ normal TSH)
hoe do you asses pituitary function
9am cortisol (to check adrenal ACTH axis) FT4, FT3, TSH Prolactin IGF1 LH, FSH, E2/Testosterone U&E, Plasma/urine osmolality
Dynamic tests
Imaging (MRI) (of the pituitary gland)
Synacthen
what is synacthen
Give someone synthestic ACTH to stimulate adrenal gland and test whether pituitary gland is working. This will show whether pituitary gland is producing ACTH. If pituitary gland stops producing ACTH then adrenal glands will become dormant and not respond appropriately to synthetic ACTH
describe the HPA axis
hypothalamus - secretes corticotropin releasing hormone (CRH) - anterior pituitary - secretes adrenocorticotropic hormone (ACTH) - adrenal cortex - secretes cortisol - multiple physiological effects
describe the secretion of cortisol
circadian (diurnal rhythm highest in morning, lowest at bed time)
why is random GH assessment of little value
as axis so dynamic
what might indicate GH hypersecretion
IGF-1
how should you measure sex hormone axis
testosterone at 9am
female sex hormones depends of the timing in menstrual cycle
what secretes prolactin
by lactotroph cells of the anterior pituitary
what inhibits prolactin secretion
hypothalamic dopamine
what mediates the effects of prolactin
Prolactin Receptor (PRLR)
what is vasopressin
anti diuretic hormone
what does angiotensin ii do
vasoconstrictor
what does vasopressin V1 do
constricts blood vessels, increasing systemic vascular resistance and arterial pressure
what does vasopressin V2 do
causes fluid re absorption in the kidneys, increasing blood volume and arterial pressure
what is dynamic testing
based on demonstrating preserved altered physiology
hormone excess - suppression test
hormone deficiency- stimulation test
why might imaging be done for the pituitary gland
AFTER BIOCHEN TESTS to localise/ characterise the disease
what can cause a cortisol deficiency
adrenal insufficiency
- primary adrenal failure (addisons disease)
- pituitary disease
what can cause cortisol excess
cushings syndrome
- ptuitary origin
- adrenal origin
- ectopic ACTH
- exogenous steroids
what are the features of cushings syndrome
Cushingoid facies Acne Hirsutism Abdominal striae & centripetal obesity Interscapular & supraclavicular fat pads Proximal myopathy Osteoporosis Hypertension Impaired glucose tolerance
what is cushings disease
Tumour arising from the corticotroph cells of anterior pituitary
what can cause ACTH independent cushings
adrenal adenoma/ carcinoma
bilateral macronodular adrenal hyperplasia
what can cause ectopic ACTH
malignancy
what can cause exogenous hormones causes cushings syndrome
oral, inhaled, topical, injectable steroid use
what test is used to diagnose cushings
too much cortisol so do suppression test:
1mg overnight Dexamethasone suppression test
(24hour urinary free cortisol)
(Midnight cortisol)
if the low dose dexamethasone suppression test fails to suppress then diagnostic of cushings
how do you distinguish the origin of cushings after a suppression test
measure ACTH
ACTH low – adrenal origin likely
ACTH raised - need distinguish Cushing’s disease and ectopic ACTH
Rise in cortisol & ACTH on CRH test indicates pituitary source (rather than ectopic)
MRI pituitary to evaluate pituitary gland
