Adrenals Flashcards
Adrenals are one of the most highly perfused organs in the body;
2000 cc/kg/min
Where do adrenal cortex and medulla arise from?
cortex–> mesoderm
medulla–> ectoderm; neural crest origin
What is the blood supply of the adrenal glands?
superior adrenal arteries–> from inferior phrenic arteries
middle adrenal arteries–> from aorta
inferior adrenal arteries–> from renal arteries
What is special about the venous drainage of the adrenal glands?
left adrenal vein is longer; drains into inferior phrenic veins–> which drains in left renal vein–> IVC
right adrenal vein is shorter; drains directly into IVC
Where does right adrenal vein drain into?
directly into IVC
Left adrenal vein drains where?
its longer
drains into left inferior phrenic vein; then left renal vein; then into IVC
what are the three layers of the adrenal cortex?
outer zona glomerulosa;
middle zona fasciculata;
inner zona reticularis
Outward to inward, what are the layers of the adrenal cortex?
glomerulosa
fasciculata
reticularis
In what part of adrenal medulla do we see an interface between sympathetic NS and endocrine system?
adrenal medulla
sympathetic fibers synapse with chromaffin cells
What converts norepinephrine into epinephrine?
phenylethanolamine n-methyl tranferase
PNMT
Zona glomerulosa makes what hormone?
aldosterone
Highest levels of ACTH and thus cortisol are seen when?
early morning when we wake
What do glucocorticoids do?
have a net catabolic effect
Aldosterone released from what zone?
zona glomerulosa
How does aldosterone get released from zona glomerulosa?
RAAS
low Na is detected in distal convoluted kidney tubule (seen in septic shock, hypovolemia)
renin is released from JGA
renin then cleaves angiotensinogen (made in liver) to angiotensin I
Angiotensin I cleaved to AT II by ACE in lungs
ATII is a potent vasoconstrictor–> stimulates aldosterone release
How does K affect aldosterone release or the RAAS?
hypo-kalemia reduces aldosterone released by suppressing renin release
hyper-kalemia; opposite effect
What does aldosterone do?
regulates circulating fluid volume and electrolyte balance
promotes Na/Cl retention in distal convoluted tubule
K/H are secreted into urine
negative feedback occurs when too much Na is seen at distal convoluted tubule, suppressing renin release
Where are catecholamines synthesized in the adrenals?
medulla
Adrenal medulla makes what?
catecholamines
Synthesis of catecholamines in adrenal medulla begins with what?
tyrosine
How is epinephrine made?
tyrosine–> L-dopa–> Dopamine–> Norepi–>Epi
Norepi is converted to epinephrine by actions of phenylethanolamine n-methyl transferase, which is located where?
chromaffin cells of adrenal medulla
and in the organ of Zuckerkandl
How are catecholamines released from adrenal medulla?
sympathetic stimulation of adrenal medulla causes release of stored catecholamines
What is the net effect of adrenal medulla catecholamine release?
deliver blood and oxygen to brain, heart and muscle at the expense of the rest of the body
fight-or-flight response
What does stimulating b1 and b2 receptors do?
b1—> receptors in myocardium–> increase contractility and increased HR
b2–> smooth muscle of uterus, bronchus, skeletal muscle arterioles –>smooth muscle relaxation
What does stimulation of a1 receptors do?
vasoconstriction seen in skin and GI system
What does stimulation of a2 receptors do?
a2 receptors found in pre-synaptic locations in CNS
attenuate SNS outflow
Plasma half life of catecholamines?
1 min
Epinephrine and norepi are inactivated by what enzymes?
MAO (monoamine oxidase)
COMT (catechol o methyl transferase)
What effect do MAO and COMT have on epinephrine and norepi and how can we use this diagnostically?
break down nore and epi to metanephrine and noremetanephrine and final product is vanillymandelic acid (VMA)
these products have longer half lives than nore and epi and they are secreted in urine
UA can be used for diagnostic purposes
What is primary adrenal insufficiency?
Addison’s dx
Addison’s dx AKA?
primary adrenal insufficiency
Sx of Addison’s dx, AKA primary adrenal insufficiency?
weakness fatigue hyperpigmentation weight loss electrolytes; hyponatremia, hyperK
What causes hyperpigmentation in Addison’s dx, primary adrenal insufficiency?
ACTH-induced melanogenesis
What causes adrenal insufficiency in Addison’s dx (primary adrenal insufficiency)?
autoimmune destruction of adrenals
Waterhouse Friedrichsen syndrome and adrenal insufficiency?
adrenal hemorrhage usually caused by meningococcal infection
more common pediatric/asplenic pts
What is secondary adrenal insufficiency?
ACTH deficiency
usually seen in pts from steroid withdrawal
How does Sheehan syndrome cause secondary adrenal insufficiency?
post-partum hemorrhage leads to pituitary infarction, which leads to decreased ACTH and adrenal insufficiency
Adrenal insufficiency in critically ill pts?
some studies suggest 30% of critically ill pts may suffer from adrenal insuficiency
usually do to adrenal ACTH resistance and decreased responsiveness of target tissues to steroids
This is a serious, life threatening event that occurs in pts with already marginal adrenal function that incur a significant stressor such as surgery or trauma or infection ;
adrenal crisis
What are symptoms of adrenal crisis?
shock
abd pain
n/v
electrolyte disturbances
Primary mechanism behind acute adrenal crisis?
menalcorticoid deficiency
inability to maintain Na and intra-vascular volume
Tx for acute adrenal crisis?
large volume resuscitation (>2 L) w/saline
hydrocortisone 100 mg IV Q 6-8 hrs or dexamethasone 4 mg IV Q 24 hrs)
How do we work up someone we suspect has adrenal insufficiency?
measure morning levels of cortisol in serum/saliva
(serum cortisol > 15.8 or saliva cortisol > 5.8 excludes adrenal insufficiency)
in pts with lower serum/saliva cortisol–> you do a high dose cosyntropin stimulation test with 250 ug of ACTH
measure cortisol levels 30-60 mins later
cortisol levels less than 18 ug/dL –> adrenal insufficiency (these pts did not respond to ACTH stimulation appropriately)
after this, a morning ACTH level is done to differentiate between primary vs secondary adrenal insufficiency
high ACTH–> primary adrenal insufficiency
low ACTH–> secondary adrenal insufficiency
How do we treat adrenal insufficiency?
the goal of maintenance adrenal insufficiency is to replace physiologic cortisol and mineralcorticoids
prednisone 5 mg/day given to replace normal cortisol
fludrocortisone 0.1 mg/day given to replace mineralcorticoids
doses can be increased if pt is undergoing a stressor like surgery or infection
What is CONN syndrome?
primary hyperaldosteronism
Primary hyperaldosteronism AKA?
Conn syndrome
Pts with Conn syndrome, primary hyperaldosteronism present with what?
resistant HTN
hypokalemia
How do pts with Conn syndrome, primary hyperaldosteronism present?
usually asymptomatic, some can have muscle cramps from hypokalemia
resistant HTN (usually on 2-4 anti-hypertensive meds)
What are the most common causes of primary hyerpaldosteronism, Conn syndrome?
unilateral aldosterone producing adenomas
b/l adrenal hyperplasia
When trying to diagnose someone with primary hyperaldosteronism, Conn syndrome what do we begin with?
plasma aldosterone concentration/ plasma renin activity
> 30–> then you create a state of hypervolemia , Na excess by loading the pt up with IV NS or salt loading and measuring aldosterone levels
if aldosterone is not suppressed, then they probably have primary hyperaldosteronism
now you need to localize the lesion by performing adrenal CT scanning (adrenalectomy in pts with clear cut CT abnormality)
then you do adrenal venous sampling if CT equivocal–> measuring aldosterone and cortisol levels in periphery and R/L adrenal veins
Surgical approach of choice for most aldosteronoma and most adrenal tumors?
laparoscopic adrenelectomy
What;s Cushing;s syndrome?
clinical features that accompany steroid excess
Most common cause of Cushing syndrome?
pharmacological steroid use for tx of inflammatory dx
What is Cushing’s dx?
steroid excess caused by ACTH-secreting pituitary adenoma
Cushing syndrome vs Cushing dx?
syndrome–> steroid excess causing plethora of symptoms
disease–> steroid excess caused by ACTH secreting pituitary adenoma
How do we screen for Cushing syndrome?
start with measuring 24 hr urine cortisol; 2 samples needed
First line antihypertensive intra-op for pheochromocytoma?
nitroprusside
Why do we perform dexamethasone suppression test?
helps us to identify cause of cushing’s syndrome
why do we have excess cortisol, is it from exogenous source, is it from ACTH secreting tumor, is it from somewhere else
Describe dexamethasone suppression test;
normal axis; hypothalamus makes CRH–> stimulates AP to make ACTH–> which stimulates adrenal make cortisol
low dose dexamethasone 1mg is given; and normal response is it will negatively feedback to brain, and adrenal and decrease CRH, ACTH and cortisol
in cases of cushing;s syndrome; where we have excess cortisol produced, the 1 mg dexamethasone suppression is not going to affect it much
so with low dose dexamethasone, if we still have high cortisol, this is suggestive of a cushing syndrome
so now we do a high dose dexamethasone suppression test with 8 mg
if we have cushing disease ( a pituitary adenoma which is makes lots of ACTH and causing adrenal to make lots of cortisol), the high dose dexamethasone will suppress the pituitary adenoma and cortisol levels will decrease
if we have an adrenal adenoma which is makes lots of cortisol, the high dose dexamethasone is not going to suppress the adrenal adenoma (but it will still suppress the CRH and ACTH, so we see low ACTH but high cortisol)
now if we have a lung cancer that is making ACTH, the dexamethasone suppression will suppress the hypothalamus and the pituitary from making CRH and ACTH, but we still have this endogenous ACTH being made that is not suppressed, so we still see high ACTH and high cortisol (the high dose dexamethasone is not able to suppress the ectopic ACTH tumor source)
Peak age of pheochromocytomas?
40-50
Classic triad of pts who present with pheochromocytomas?
headache
diaphoresis
palpitations
**HTN also present, can be episodic vs sustained
Rules of 10s of pheochromocytomas?
10% malignant
10% bilateral
10% extra-adrenal
10% familial
How do we diagnose pheochromocytomas?
detection of 24 urine for catecholamines
Most common peri-operative changes witnessed with pheochromocytomas is?
intra-op; HTN
post-op; hypotension
intra-op; anesthetic induction and manipulation of tumor
post-op; due to state of hypovolemia due to excess circulating catecholamines; sudden withdrawal from this stimulus causes arteriolar vasodilation
How can we prevent the hemodynamic changes assc with pheochromocytomas intra-op and post-op?
use of a-adrenergic blockade as soon as the diagnosis of pheo is made
phenoxybenzamine is used; 10 mg twice/daily; two weeks before planned surgery
How does phenoxybenzamine work in pheo?
non-specific, irreversible A-adrenergic antagonist
SE: postural hypotension, nasal congestion
**b-blockers can be used after adequate a-blockade, should never be used as first line drugs
Tx for pheo?
surgery is curative >90% of cases
most can be done laparoscopically
**lap contraindicated if there is local invasion
What % of pheochromocytomas are familial?
20-30%
Are pheochromocytomas malignant?
2-40% are
What are incidentalomas?
incidentally discovered adrenal masses
are discovered thru imaging for non-adrenal causes
How do we work up incidentalomas?
size criteria + hormonal evaluation
For incidentalomas whats the size cutoff for surgical removal?
remove all incidentalomas >5 cm
consider strongly removal of masses 3-5 cm
**if observation chosen, imaging should be done 6-12 months
What are suspicious imaging characteristics of incidentalomas that would warrant removal?
heterogenous
high attenuation
irregular margins
Do we use FNA for adrenal masses suspected of being malignant?
NO
What are some cancers that mets to adrenal glands due to their rich vascular supply?
LUNG
Gi tract
Benefits of laparoscopic adrenalectomy vs open?
less pain
less bleeding
less hospital stay
Conversion rate from laparoscopic to open adrenalectomy?
5%
When is an adrenalectomy performed open?
tumor suspicious for malignancy
size > 8cm
clinical feminization
local or vascular invasion
mets
regional adenopathy
What’s Palmer’s point?
mid-clavicular, 2 inch inferior to costal margin
When do we use adjuvant mitotane for carcinoma of adrenal?
vascular/capsular invasion
intra-op tumor spillage
high-grade disease
After removal of an adrenal carcinoma, what type of surveillance do we do?
abdomen/pelvis/chest every 3 months for 2 yrs
every 4-6 months for 5 yrs
What ectopic lesions cause Cushing syndrome?
small cell lung ca
Causes of Cushing syndrome?
pituitary lesions
adrenal adenoma
ectopic tissue; small cell lung Ca
When is laparoscopic adrenalectomy not performed for adrenal lesions?
relative contraindication for lesions 6-8 cm
absolute contraindication is local invasion of lesion to surrounding structures
Whats the difference between adrenocortical carcinoma stage I vs stage II?
related to size
whether tumor is less than or greater than 5 cm
During intra-op manipulation of an adrenal carcinoma, you get tumor spillage, what do you do?
add mitotane adjuvantly
What do the three zones of the adrenal cortex make?
zona glomerulosa–> mineralcorticoids (aldosterone)
zone fasciculata—> glucocorticoids (cortisol)
zona reticularis–> sex hormones
medulla–> catecholamines
What CT findings are concerning for an adrenal ca?
> 20 hounsfield units
lesion has calcifications
size > 4 cm
unilateral location
heterogenous appearance on CT
Most common cause of Cushing’s dx is?
iatrogenic due to exogenous steroid use
2nd most common; ACTH producing pituitary tumor
Most common cause of Conn syndrome (primary hyperaldosteronism?)
b/l adrenal hyperplasia (need to localize is with thin cut adrenal ct; venous sampling if CT inconclusive)
(second most common cause is unilateral adrenal adenoma; tx is lap adrenalectomy)
b/l adrenal hyperplasia managed with aldosterone antagonists
Most commonly use screening test for Conn syndrome; hyperaldosteronism?
aldosterone; renin ratio; cutoff is 30
What is Cushing’s dx and what is the tx?
ACTH secreting pituitary tumor
trans-sphenoidal resection usually curative in 75%
remission rates can be improved by re-operative vs pituitary radiation
Advantage of posterior laparoscopic retroperitoneal adrenalectomy approach?
good for pts that have had prior abdominal surgeries
good for pts who need b/l adrenalectomies
Gold standard initial test when you suspect someone has Cushing syndrome (hypercortisolism)?
24-hr urine collection for free cortisol
> 300 mcg/day are diagnostic
once you confirm pt has cushing syndrome; gotta check an ACTH level
if ACTH is low, cortisol is high–> adrenal adenoma or hyperplasia
if ACTH is high, cortisol is high–> pituitary adenoma vs ectopic ACTH tumor (high dose dexamethasone test then done)
When MEN2A and MEN2 disorders are involved, when do we perform thyroidectomies for pts?
MEN2B; thyroidectomy before 1 year old
MEN2A; thyroidectomy before 5 years old
Most common primary tumor to mets to adrenals is?
lung
MC cause of hyperaldosteronism? Conn syndrome?
bilateral adrenal hyperplasia
2nd most common cause is adrenal adenoma
Nitrogen balance formula?
protein/ 6.25 - (UUN +4)
