Adrenal gland Flashcards
cellular zonation of adrenal cortex
zona glomerulosa - mineralcorticoids (aldosteron)
zona fasiculata - glucocorticoids (cortisone, corisol, corticosterone)
zona reticularis- sex hormones (androgens, estrogens)
chromaffin cells - catacholamines ( NE & EPI)
Adrenal gland general function
affect blood pressure & electrolytes within the blood
Adrenal regulation
hypothalamus - CRH
pituitary gland - ACTH
adrenal cortex- cortisol feedback loop
precursor for adrenal gland hormones
cholesterol!
cortisol feedback mechanism
hypothalamus –(CRH)–> anterior pituitary –(ACTH)–>adrenal cortex–> cortisol!
cortisol inhibits hypothalamus & anterior pituitary
zona glomerulosa (outer 10%)
mineralcorticoids
aldosterone - enzyme aldosterone synthetase active
stimulated by ACTH & renin axis system
zona faciculata (middle 75%)
glucocorticoids - cortisol, cortisone, DHEA
stimulated by ACTH
zona reticularis (inner 10%)
androgens like DHEA are sulfated to DHEAS (main androgen)
stimulated by ACTH
Renin-angiotensin system (RAS)
renin is released from kidney juxtaglomerulus apparatus
renin acts on angiotensin-ogen from liver to get angiotensin I
angiotensin I is converted by ACE (lung) to angiotensin II ( vasoconstrictor)
what does Renin-angiotensin system (RAS) lead to in the body?
aldosterone release from adrenal cortex & resulting absorption of Na+ from the proximal tubule of the kidney
& increase in osmotic pressure & improvement of blood pressure
cortisol general
made in F-zone w/ adequate 17-alpha-hydrolase activity
dinural variation - regulated by ACTH
90% protein bound (CBG)
cortisol effects
stimulates gluconeogensis & glycogenesis decreasing protein synthesis increase blood glucose decrease calcium absorption increases adipose fat tissue influences CNS pain perception & sense of well being slows inflammatory response
cortisol & ATCH diurnal cycles
lowest at midnight & highest around 8 am
adrenal insufficiency labs show:
decreased cortisol
increased ACTH & CRH
the increased ACTH leads to adrenal gland hyperplasia & increased androgen production
Diseases associated with aldosterone
congenital adrenal hyperplasia
isolated hypoaldosteronism
hyperaldosteronism
diseases associated with cortisol
addison’s disease
cushings syndrome
Congenital adrenal hyperplasia
inherited family of enzyme disorders
lead to decreased cortisol & decreased aldosterone
defect in 21-hydroxylase enzyme & causes a build up of 17-hydroxy progesterone & androgens bc cortisol is low
treat with replacement cortisol
isolated hypoaldosteroneism
only aldosterone is decreased
see in adrenal gland destruction, chronic heparin therapy etc
patients with diabetes, mild metabolic acidosis, increased metabolic acidosis & elevated serum K+ with low urinary K+
hyperaldosteronism
excess aldosterone
may develop metabolic alkalosis, hyper-tension & increased serum K+
determine PA/PRA (plasma aldosterone/plasma renin activity)
PA/PRA >25 indicative for disease
urinary excretion of K+ suggests:
hyperaldosteronism
especially >30 mEq/L
upright PA/PRA ratio (>25)
hyperaldosteronism
no Captopril suppression suggests:
hyperaldosteronism
Cortisol insufficiency
addisons disease
decrease cortisol w/ weakness, fatigue, anorexia, diarrhea, nausea
often 90% of cortex gland is destroyed
lab values for addison’s disease
decreased Na+, glucose, cortisol
increased K+, ACTH, calcicum
prerenal azotemia
mild metabolic acidosis
causes of addisons
autoimmune (70%)
infections (tuberculosis 20%), hemorrhage, infiltrative processes, metastasis
cortisol insufficiency testing
when decreased cortisol w/ increased ACTH on 8 am specimen - need stimulation tests
Cosynthopin
stimulates both cortisol & aldosterone secretions
look for rise in cortisol when given 250 ug
Metyrapone
give at midnight, blocks 11-B-hydroxylase & look for rise in 11-DOC while cortisole decreases
normal response to cosynthopin but not to metyrapone?
look for secondary adrenal insufficiency (ACTH secreting tumor)
Addison’s disease general
primary adrenal insufficiency - gradual destruction of adrenal gland
90% loss before symptoms
secondary adrenal insufficiency- most common form of the disease; Lack of ACTH
Cushing’s syndrome general
prolonged exposure to high levels of cortisol
leads to glucose problems, immune suppression & depression
high cortisol & low ACTH if primary
common causes of cushings
ACTH secreting pituitary adenoma (68%)
autocortisol production by adrenal tumor (17%)
excess ectopic ACTH or CRH production (15%)
Assay methods
2 site IRMA assay for ACTH
ELISA for cortisol
how to separate ACTH-dependent from ACTH-independent cushings syndrome
ACTH dependent cushings: ACTH >15 pg/uL & cortisol >15 ug/L
Cushing’s syndrome symptoms
upper body obesity: round face, increased fat about neck, thinning of arms & legs
fragile skin: easy bruising etc
hypertension & diabetes (!!!)- secondary diabetic condition
excess hair growth & fertility issues
Cortisol Suppression testing w/ Dexamethasone
differentiates between pituitary & ectopic ACTH secreting tumor
pituitary is 90% suppressed but tumor is not!!
Cushing’s lab testing
excess cortisol, LOSS OF DIURNAL VARIATION, resistance to suppression test
urine free cortisol levels on 24 hr urine
serum cortisol @ 8 am & 4 pm
DHEA & DHEAS
formed in zona reticularis (cholesterol based) & are precursors to number of androgens: androstenedione, testosterone, 5-dehydrotestosterone (5-DHT) & estrogens
men get 5% of their testosterone from adrenal gland
women get 40-65% of their testosterone from the adrenal gland
Androgen excess
overproduction can lead to infertility & masculization in women
over production inhibits pituitary gonadotropin hormone production leading to loss on needed hormones
adrenal release of cortisol occurs when the pituitary releases?
ACTH
aldosterone is synthesized in the adrenal cortex layer____?
zona glomerulosa
Catecholamine synthesis location
adrenal medulla
Catecholamines (2)
epinephrine & norepinephrine
Epinephrine
made form tyrosine (!)
increases cardiac output, blood pressure
direct blood to muscles & brain
mobilizes fuel from storage to action
rate of norepinephrine to epinephrine
9:1
enzyme that converts norepi to epi
phenylethanolamine N-methyl transferase or PNMT
this is the control point in epinephrine synthesis
epinephrine cell action
interacts with alpha-adrenergic receptors on cells that cause a cascade of events on the interior of the cell
produce more ATP etc
Catecholamine degradation
3 mechanisms:
- reuptake into secretory vesicles
- uptake in nonneuronal cells (mostly liver)
- degradation through 2 enzymes lead to formation of metanephrine & VMA from free catecholamines
2 enzymes that produce metanephrine & VMA from free catecholamines
catechol methyl transferase or COMT
monoamine oxidase MAO
methods of analysis of catecholamines
HPLC, fluorometric methods, or LC-MS/MS
used for urinary 24 hr metabolites of catecholamines
reliable & not altered by age/gender
drugs can interfere with fluormetric methods
color methods - test VMA
special urine collection, NO BANANAS or VANILLA up to 3 days prior
causes of sympathetic hyperactivity
elevated epinephrine autonomic dysfunction panic attacks stress response drugs food with tyramine PHEOCHROMOCYTOMA
Pheochromocytoma
tumor of chromaffin cells
hypertension present, high levels of catecholamines & will NOT be suppressed by CLONIDINE
testing for pheochromocytoma
24 hr urine test for metanephrines (!) & catecholamines
clonidine (should suppress epinephrine) suppression test is 92% accurate
