Feb1 M1,2-Adrenal Gland Flashcards
adrenals crucial fct
response to stress
adrenals embryo origin, parts and relative volume
cortex 10%
medulla 90%
medulla vs cortex (adrenals) molecules made
cortex: steroids
medulla: catecholamines
circulation to adrenals and word describing it
suprarenal arteries coming along cortex and then dive 90 degrees inside cortex to medulla. called centripetal circulation
importance of centripetal circulation on adrenal fct
some steroid hormones produced in cortex released there and have enzymatic influence in adrenal medulla
part of adrenals that is in ANS and why
medulla. preganglionic synapse on it with Ach (medulla acts on ganglion). medulla releases NE and E directly in circulation rather than blood stream
name of nerves from which the medulla is derived and spinal origin
splanchnic nerves, coming from T8 to T11 form the medulla
precursor molecule to making NE and E and diff intermediate molecules
tyrosine. L-DOPA. dopamine. NE. E.
2 important enzymes (rate limiting) in adrenaline biosynthesis and which rx they control
- tyrosine hydroxylase (tyrosine to L-DOPA)
- PNMT (NE to E)
example of steroid influence from cortex on medulla
in response to stress, cortisol from cortex goes to medulla and increases PNMT activity (more adrenaline made)
4 NE and E receptorss
alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors
beta 1 R location and effect and pharmaco principle
heart. chronotrope and inotrope effect.
for BP and angina, give beta 1 specific antagonist. otherwise get bronchoconstriction
beta 2 R location and effect and pharmaco principle
SM dilation. in lungs, must give beta 2 specific agonists for asthma otherwise, tachycardia as side effect
rule of thumb on effect of alpha activation
vasconstriction and SM constriction
rule of thumb on effect of beta adrenergic activation
SM relaxation and vasodilation
pheochromocytoma symptoms
pheochromocytoma spells: very high BP, lapitations, anxiety, headache, pallor and sweating
only adrenal medulla pathology that exists and specific definition
pheochromocytoma: tumor (growth) of chromafin cells in adrenal medulla
2 types of pheochromocytoma, % and definition
90% are in adrenal medulla
10% can happen in any SS ganglia along the aorta (called paraganglioma)
lab to dx pheochromocytoma
can measure metabolites of NE and E (metanephrines and vanilmandelic acid (VMA)) in 24h urine excretion
steps in pheochromocytoma investigation
- 24h urine collection: catecholamines and metanephrines
- MRI scan if elevated
danger of pheochromocytoma in surgery
can release NE and E a lot and have hypertensive crisis
special test used in paraganglioma (to scan it)
MIBG scan
is pheochromocytoma indiv in vasodilation or vasoconstriction and why
vasoconstriction bc high NE and E causes a predominant alpha effect
in PCC surgery prep, 2 steps and why
- alpha blocker to vasodilate
- replenish plasma volume (high salt diet)
Because otherwise, removing PCC will just vasodilate and will put in low volume state
mistake in PCC surgery prep and why + why would this happen
beta blocker. (beta adrenergic R have vasodilative effect so blocking them will cause constriction and oppose alpha-blocker effect.
could happen if had beta blocker for BP or wtv
when would give beta blocker in PCC surgery prep
might give it, after alpha blocker and fluid, for the tachycardia
diseases of adrenal insufficiency
none. don’t exist bc SS system can do its work
3 layers of adrenal cortex
zona glomerulosa
zona fasciculata
zona reticularis
zona glomerulosa fct and influences
make aldo (mineralocorticoids) in response to AT2 and K+ (and ACTH to a lesser extent)
zona fasciculata fct
make cortisol (glucocorticoids) in response to ACTH
zona reticularis fct
androgen pathway. make DHIAS (dehydroepoiandrosterone), a sex hormone precursor in males
common precursor to all cortex steroid hormones and why
cholesterol. from it, can produce any of 3 hormone types in adrenal cortex via enzyme pathways
clinically relevant enzyme in cortex and what pathway
21-OH (21-hydroxylase)
In cortisol pathway AND aldosterone pathway
mechanism of action of steroid hormones
bind receptor in cytoplasm or nucleus and this R acts as TF, affecting gene transcription
(no membrane R)
feedback effect of cortisol
- inhibits anterior pituitary (less ACTH)
- (to lesser extent), inhibits hypothalamus (less CRF)
precursor molecule of ACTH and how it is processed in pituitary gland vs in neurons
POMC (pro-opio-melanocortin)
pit: broken in many parts, one of which is ACTH
neurons: broken in many parts, one of which is MSH (melanocyte stimulating hormone)
symptom visible in any condition where ACTH is elevated and why
skin pigmentation. bc POMC needed to make the high ACTH also made MSH
3 functions of ACTH on adrenal gland
- more steroid secretion
- increased blood flow through adrenal
- trophic effect (increase size of adrenal)
consequence of low ACTH for weeks
adrenals are deprived of ACTH = become atrophic and no longer make cortisol
can you reverse adrenal atrophy due to ACTH deprivation
reversible but no ACTH for weeks so will have cortisol prod defect for a moment
pattern of cortisol secretion during the day + importance
low at night, rises a lot at 8 am. peak at 9 am. low in the afternoon.
Important clinically for how blood test done
cortisol in the blood + importance
95% bound to transcortin (glucocorticoid-binding protein) inactive
5% unbound (free) = active
2 main effects of cortisol (of glucocorticoids)
- catabolic effect
- anti-inflammatory
effect of cortisol on catabolism (think macromolecules categories)
- higher gluconeogenesis in the liver (glucose creation from other nutrients)
- fat redistribution
- prot breakdown in muscle
- increased gastric acid and pepsin (gastric ulcers)
cortisol effect on gonads
amenorrhea (absence of menstrual period)
cortisol effect on CNS
many effects
too much = euphoria
lacking = depression and fatigue
pathologies of cortisol secretion
Cushing’s syndrome: hypersecretion
Addison’s disease: lack of cortisol
Cushing’s syndrome on physical
think skin, thin arms, cushinoid fat distribution (abdomen and central), bruising in arm, muscle weakness, fleshoplethora (redness on cheeks), obesity, immunosuppresion
Cushing’s physical in children main feature
growth stops
abdominal features on Cushing’s physical and reason
violacious stretch marks because of rapid weight gain + protein catabolism so skin near viscera
very important category of symptoms of Cushing’s syndrome
neuropsychiatric manifestations (insomnia, depression, psychosis, impaired cognition and memory)
Cushing’s dx and management approach (3 steps)
- dx CS
- find cause (ACTH dependent vs independent + find source of ACTH dependent)
- imaging of adrenal or pituitary (after source is known)
cortisol rhythm in the day in CS patients
constantly elevated cortisol levels (loss of diurnal rhythm)
pituitary tumor vs adrenal and ectopic tumor in CS
pituitary tumors are partially autonomous bc can still have feedback inhibition at higher than normal cortisol level
adrenal and ectopic = no feedback
4 investigations (screening tests) (where any 1 positive of the 4 = CS)
- elevated 24h cortisol
- non suppressed morning cortisol after night low dose dexamethasone
- plasma cortisol in morning and evening (loss of circadian rhythm)
- late-night salivary cortisol evelated
principle of dexamethasone test for CS screening
it inhibits cortisol in the morning (puts it to less 50 normally), given at night and cortisol low in the morning
3 etiologies (categories) of CS
pituitary ACTH, ectopic ACTH or ACTH independent
most common cause of CS and % + distribution of pathologies
70% are pituitary ACTH dep
microadenomas 95%
macroadenomas 5%
other cause of ACTH dependent CS + pathologies
ectopic ACTH or CRH
- small cell lung CA
- carcinoids (neuroendocrine tumors): lungs, pancreas, thymus
ACTH independent CS: pathologies
- exogenous (taking cortisol)
- bilateral hyperplasia
- unilateral (adrenal adenoma. adrenal CA is very rare)
how to check if CS is ACTH dependent or independent and interpretation (2)
-ACTH assay
low ACTH = ACTH indep (tumor or exogenous)
-high dose dexamethasone suppression. if cortisol suppressed = pituitary tumor
when to use high dose dexamethasone suppression test and interpretation
- dx CS bc pit not suppressed by low dose dex
- assay gave high ACTH
- high dose dex to check if pituitary or ectopic. ACTH suppressed by high dose dex = pituitary
assay giving low ACTH (suppressed ACTH) points to what generally
to adrenal prob (adenoma or CA)
NO NEED to do high dose dex. we know it’s not ACTH dependent
imaging to do it find out ACTH is suppressed for ex (low plasma ACTH)
CT of the abdomen
dexamethasone and prednisone: type of molecule and why high dose dexamethasone test when high ACTH
glucocorticoids. high dose dex test checks if this glucocort. can suppress prof of ACTH (it can if ACTH comes from pit)
pharmaco use of glucocorticoids
- inflam and autoimmune conditions
- rheumatoid arthritis
- severe asthma
- certain lymphatic system cancers
how to stop a high dose long course of glucocorticoids (ex 15 mg prednisone daily)
lower dose over 9 months. bc adrenals atrophied due to no ACTH all the time. (exogenous glucocort suppresses pituitary) so have to avoid adrenal crisis
adrenal crisis def and when it can happen
lack of endogenous cortisol. if stop and exogenous glucocorticoid immediately
Addison’s disease main symptoms
- fatigue
- nausea
- anorexia
- low BP
- hyperpigmentation
Addison’s main cause
autoimmune destruction of the adrenal cortex: adrenal insufficiency, lack of adrenal steroids
Addison’s pts risk in surgery
can get severe hypotension (hypotn crisis) bc can’t mount stress response needed in surgery
ACTH level in Addison’s and why
high bc no cortisol and glucocorticoids to suppress it
why hyperpigmentation scars in Addison’s
high ACTH production (so MSH came with it too)
2 categories of adrenal insufficiencies and Addison’s in which
primary and secondary
Addison’s is primary
cause of disease in secondary adrenal insufficiency and ACTH and cortisol levels
destruction of pituitary (or also hypoth problem). low ACTH, low cortisol
dx test for adrenal insufficiency and can it differentiate primary from secondary?
ACTH stimulation test. (give ACTH) if no cortisol response, primary insufficiency
if weak cortisol response, secondary. (shows it’s due to adrenal atrophy) bc there is some response. If NO cortisol response, primary.
why ACTH stim test is not the best for adrenal insufficiency dx + primary vs secondary
if problem in axis hasn’t been going for long enough, adrenals not atrophied and will respond normally to ACTH (we’ll think they’re normal)
what test + its steps used to diff primary vs secondary adrenal insufficiency with precision (gold standard but rarely done)
insulin stimulation test.
- make sugar very low by giving enough insulin
- at same time, measure cortisol and ACTH
interpretation of insulin stimulation test (normal vs abnormal results)
normal result = rise in ACTH and cortisol in response to stress
abnormal = no rise in ACTH = hypopituitarism caused 2ndary insufficiency
adrenal insufficiency: summary of dx tests (3)
- ACTH level (low in 2ndary, high primary)
- ACTH stim test (weak cortisol = 2ndary, 0 cortisol = primary)
- insulin stim test (no ACTH rise = pit problem, 2ndary)
treatment of primary adrenal insufficiency (2)
- cortisol (hydrocortisone or prednisone or wtv) for life
- fluorinef (aldo pill)
central adrenal insufficiency treatment
- cortisol
- NO fluorinef (RAAS still functioning)
cause of 2ndary adrenal insufficiency other than HP axis and ACTH and cortisol levels
exogenous corticosteroids.
ACTH is low (suppressed)
cortisol LOW (not high enough bc have adrenal insufficiency)
treatment of central adrenal insufficiency due to HP axis being suppressed by exogenous corticosteroid
give only glucocorticoids (to reach good lvl)
acute primary adrenal insufficiency treatment (how compares to chronic)
IV hydrocortisone and fluid replacement (no need for fluorinef)
what to check regularly in patients on glucocorticoids
diabetes, bone health
what stimulates aldo secretion
- AT2 mainly
- rise in K+
- ACTH (to lesser extent)
actions of AT2 in the body
- aldo secretion
- arteriolar vasoconstriction
2 types of hyperaldosteronism and how to differentiate
primary: low renin
secondary: high renin
causes of primary hyperaldo
- adrenal adenoma
- bilateral adrenal hyperplasia
primary hyperaldo clinical presentation
htn, hypokalemia
secondary hyperaldo causes
low flow to kidneys (CHF, RAS, cirrhosis, nephrotic syndrome)
rarely renin prod tumor
3 main endocrine causes of resistant htn to check in young htn pts
- primary hyperaldo
- Cushing’s syndrome
- PCC
cause of 21-hydroxylase deficiency
2 mutations in the gene (autosomal recessive condition)
primary consequence of 21-hydroxylase deficiency
adrenal pathology and no more cortisol and aldosterone produced
labs in 21-hydroxylase deficiency
hyponatremia
hyperkalemia
treatment of 21-hydroxylase deficiency
hydrocortisone, fludrocortisone (aldo and cortisol effect), NaCl
reason for weird looking genitalia in newborn with 21-hydroxylase deficiency
blockage due to 21-hydroxylase deficiency leads to accum of precursors (17 hydroxy progesterone) so increase of androgen pathway
general category of diseases in which 21-hydroxylase deficiency is included
congenital adrenal hyperplasia
ACTH levels in congenital adrenal hyperplasia and why + consequence
very high bc low cortisol. lot of precursors made, shuttled to androgen pathway
treatment of congenital adrenal hyperplasia
long term glucocorticoid and mineralocorticoid replacement
what are the hormones lacking in primary vs secondary or central adrenal insufficiency
primary: cortisol and aldo
secondary: ONLY glucocorticoids are lacking (same for acute primary)
