Pathology of the Adrenal Glands- Hillard Flashcards
where are the adrenal glands
above the kidney in a superior location
what are the parts of the adrenal gland
capsule, adrenal cortex, adrenal medulla
what is the blood supply to and from the adrenal glands
arteries: suprarenal arteries
vein: adrenal vein
has a robust blood supply so it is less disturbed by interuptions to blood flow
what are the three parts of the adrenal cortex
zona glomerulosa
zona fasiculata
zona reticularis
the zona golmerulosa creates _
mineralocorticoids: aldosterone which helps to increase salt retention by the kidney
the zona fasciulata creates _
cortisol which is released during times of stress
and increases glucose in the blood
the zona reticularis creates
androgens
an increase in androgens will have a _ affect
virilizing/masculining effect
the adrenal medulla creates _
catecholamines (epinephrine and noreepinephirne)
cushing syndrome is caused by an excess of?
glucocorticoid cortisol
what are the symptoms of cushing disease
HTN- multifactorial cortisol increases vascular sensitivity and drives renin production
fat redistribution- central obesity and fat behind the neck, cheecks, and side of head (moon facies)
secondary diabetes - increased blood sugar levels and increased glucose in the urine
catbolic state breaking down bone and collagen - skin thinning and osteoporosis
mood swinfs
depressed immune system
hirtuism
cortisol is a potent driver of _
glucoenogenesis and created glucose from energy stores
high cortisol causes the body to be in a _ (anabolic/catabolic) state
catabolic
breakdown bone and collagen
describe the HPA of cortisol
increased stress will stimulate CRH release from the hypothalamus, which acts on the the anterior pituitary to release ACTH. ACTH then acts on the adrenal gland (zone fasiculata) to produce cortisol
cortisol has negative feedback on the AP and the hypothalamus
what are the two types of cushing syndrome
EXOGENOUS/ IATROGENIC- too much cortisol being absorbed
ENDOGENOUS- body is producing too much cortisol
what is cushing disease
problem in the pituitary or higher
usually a pituitary adenoma that causes hyperfunctioning: cortioctrophic adenoma that creates too much ACTH and causes excess cortisol release from the adrenal glands
what is ectopic cushing disease
ACTH is produced in an ectopic location most notably due to a paraneoplastic syndrome: small cell carcinoma of the lung
what is an adrenal gland cushing syndrome
this is when excess cortisol is being produced from the adrenal glands
most commly from adrenal adenoma, carcinoma or hyperplasia
does adrenal cushing disease dependent on ACTH
no, it would actually be suppresed by cortisol negative feedback
cushing disease and ectopic cushing disease are dependent on ACTH - all of them are endogenous
what is the most common cause of ACTH INDEPENDENT endogenous hypercortisolism
adrenal adenomas
how does an adrenal adenoma look?
well demarcated and yellow cut surface
impossible to tell grossly if it is nonfunctional or secreting cortisol or secreting aldosterone
how do adrenal adenomas look under the microscope?
they are well circumscribed tumors
tumors recapitulate cells in the adrenal cortex- can have atypica
- atypia is not an evidence of malignancy
must look for invasion/metastasis to rule out malignancy
hyperplasia of the adrenal gland is most commonly seen with?
pituitary cushing syndrome and paraneoplastic/ectopic cushing syndrome
if hyperplasia of the adrenal gland is the only presenting feature then it may be a result of what genetic disease
mcCune albright
or carney complex (PRKAR1A, lactotrophs and somatotrophs)
what is mccune albright syndrome
this is replacement of bone with firbous tissue and cafe au lait spots with precoccious puberty
what is carney complex
mucocutaneous pigmentation and myocmatous tumors
what does the adrenal gland look like when given exogenous cortisol/corticosteroids
atrophic and shrunken
why do the adrenal glands become atrophic and shrunken with chronic corticosteroid use?
because they no longer need to produce steroids there will be a loss of cortical layers/cells
must taper off corticosteroids
paraneoplastic cushing syndrome is most often caused by?
small cell lung carcinoma
lung is the first source to consider if there is ectopic cushing syndrome
how would you screen someone for cushing syndrome
start by taking a good history and physical
make sure they are not taking any exogenous steriods
rule out physiological reasons as to why there is increased cortisol ( pregnancy, obesity)
what are the screening tests for cushing syndrome
low dose dexamethasone suppresion test
24 hr urinary cortisol
salivary cortisol (late night)
after the diagnosis of cushings syndrome is made what do we do now?
check ACTH levels to see if it is ATCH independent or dependent
if cushing syndrome is ACTH independt ACTH levels will be?
suppressed
then you should do imaging of the adrenal glands
if ACTH is dependent in cushing syndrome meaning ACTH levels are?
you then do what?
normal to high
high dexamethasone suppresion test
pituitary MRI
inferior petrosal sinus sampling
in a dexmathasone suppresion test what happens
in a normal person this should suppress ACTH
in a pituitary adenoma is acth suppresed in a high dexamethasone test?
yes
then it is cushing disease!
in ectopic acth tumors does a dexamethasone test suppress ACTH
no
so check the lungs for paraneoplastic syndrome: small cell carcinoma of the lungs
what does a pituitary MRI do?
it checks for cushing disease (pituitary tumor) by looking at the pituitary
what is an inferior petrosal sinus sampling
measuing ACTH directly from the veins rhat drain the pituitary gland to check for tumor
aldosterone is normally released in response to _
renin
renin is released by the kidney when?
when there is low volume or low blood pressure
renin converts angiotensionogen to
angiotensin I
angiotensin I is converted to angiotensin II by?
angiotensin converting enzyme (ACE)
angiotension II stimulates the adrenal gland to release _
aldosterone
what are the actions of aldosterone
causes the kidney to absorb sodium and water and increases blood volume
what is hyperaldosteronism
this is chronic elevation of aldosterone
what are the types of hyperalldosteronism
primary- adrenal gland produces too much aldosterone and renin is low
secondary- extradrenal cause of too much aldosterone and renin is high
explain primary hyperaldosteronism
the adrenal gland will produce too much aldosterone which will raise blood pressure and blood volume, this in turn will adequately perfuse the kidney and cause renin to decrease
explain secondary hyperaldosteronism
decreased blood flow to the kidney (globally or locally) can cause renin to increase and increase aldosterone
what is the most common cause of primary hyperaldosteronism
idiopathic hyperaldosteronism where there is hyperplasia of the zona glomerulosa
what is the second most common type of primary hyperaldosteronism
an aldosterone secreting ADENOMA in the zona golmerulosa
aka conn syndtome
what is a rare cause of primary hyperaldosteronism
glucocorticoid suppresible primary hyperaldosteronism
what is glucocorticoid suppresible primary hyperaldosteroinsm
hybrid cells ar ein the zona glomerulosa due to a genetic abnormality and release aldosterone in reponse to ACTH
so aldosterone is increased when ACTH increases
does the dexamethasone test suppress ACTH in glucocorticoid suppresible primary hyperaldosteronism
yes, once ACTH is suppressed then aldosterone release will decrease from teh hybrid cells
what are the symptoms of primary hyperaldosteronism
hypertension and hypokalemia
hypokalemia can cause a metabolic alkalosis
low postassium- can cause muscle cramps, neuromusclar isssues, weakness
aldosterone increases Na+ absorption and K+ excretion
in practice hypokalemia is inconsistently seen
what is the screening test for primary hyperaldosteronism
aldosterone to renin ratio
ratio should be high
if the aldosterone to renin ratio is high you should do what confirmatory test?
a saline infusion (aldosterone suppresion test)
if aldosterone does not suppress you have primary hyperaldosteronism
adrenal adenomas in primary hyperaldosteronism can show?- on hsitology
spironlactone bodies on histology
used to treat an adrenal adenoma (conns syndrome)
what do spironolactone bodies look like?
circular whorled eosionophilic structures in the tumor that represent endoplasmic reticulum material bound to aldosterone
secondary hyperaldosteronism is caused by conditions that activate?
what are three things that can cause secondary hyperaldosteroinsim
activate the RAS system from decreased blood flow to the kidney or from global hypovolemia and edema
renin producing tumor
what can lead to decreased renal artery perfusion
renal artery stenosis, renal fibromusclar dysplasia
what can lead to global hypovolemia and edema
heart failure and neprhotic syndrome
normal pregnacy can also induce an increase in renin and aldosterone how?
due to an increase in ovarian secretion oand decidual release and high estrogen levels which drive production of angiotensionogen
congenital adrenal hyperplasia is a group of autosomal _ disorders in wheich the enzyme invovled in the biosynthesis of _ is deficent
recessive
cortisol
what mutation is involved in CAH and what enzyme is deficient
CYP21A2 is mutated
21-hydroylase def
congenital adrenal hyperplasia typically presents at _ and shows what sigsn?
birth
decreased cortisol
decreased aldosterone
virulization
why does adrenal hyperplasia occur in CAH
there is decreased cortisol the hypothalamus is no longer inhibited and will create more CRH and the pituitary wont be inhibited from secreting ACTH which will act on the adrenal gland and cause hyperplasia/enarlgement
21 hyrdoylase converts precursor products that are originally derived from _ to aldosterone and cortisol
cholesterol
with a 21 hydroxylase def there is an enzymatic def in the conversion of
progesterone becoming 11-dexycorticosterone and eventually aldosterone
17-hydroy progesterone becoming 11-doexycortisol and eventually cortisol
because of the 21 hydroylase def in CAH what happens
17- hydroxyprogesterone is converted to androsteniodione and eventually androgens like testosterone and give virulizing effects
an infant with CAH will look?
clitoral enlargment labial fusion in XX
penis enlargement in XY
usually just effects external genitalia
salt wasting
low aldosterone leads to
salt wasting and hyperkalemia
low cortisol leads to?
medullary defects, low epinephrine, hypotension and collapse
intraadrenal glucocorticoids are necessary for _ production
catecholamines (epineprhine and norepinephrine)
what test is diagnositc for CAH
elevated 17 hydroxyprogesterone (17 OHP_
heel puncture taken 2-4 days after birth
what are the three types of CAH
classic form with salt wasting- present in neonate
simple virulizing- presents in neonates
non-classic- late onset (present in adolescents/adult)
usually the 21 def is shown on the neonatal newborn screen
what is acute primary adrenocorticoal insufficiency
there is a problem in the adrenal gland that causes a lack of adrenal hormone from being produced
doesnt make mineralocorticoids or glucorticoids like it should
what are the causes of acute primary adrenocortical insuficiency
chronic steroid use rapid withdrawl
massive adrenal hemorrhage
waterhouse friederichsen syndrome
why does excogenous steroid use and withdrawl cause acute primary adrenocortical insufficiency
use of steroids results in atrophy of the adrenal gland, upon removal of them the adrenal gland cannot make the hormones it needs
how does acute adrenal hemorrhae cause adrenocortical insufficiency
due to the size and vasculatitiry of the adrenal gland at birth any time hypoxia occurs the adrenal gland will recieve more blood and cause increased pressure and hemorrage into the adrenal gland damaging it
what is waterhous friederichsen syndrome
bilateral adrenal hemorrhage that is a result of neisseria meningitis (infection)
can be causse dby any bacterial organism
exogenous steroids can cause _ and rapid withdrawl of steroids can cause
cushing syndrome
acute primary adreocortical insufficency
neisseria meningitdis is manifested with DIC what is this?
intravascular coagulation that causes abnormal clotting through the bodys blood vessels that can ruputre in the adrenal glands
key symptoms of primary adrenocaortical insufficiency
abdominal pain, nausea, vomiting, weakness, lethary, shock , and confusion
acute adrenocortical insufficiency can also be seen in chronic adrenocortical insuffiency when there is a major stressor
what is chronic adrenocortical insufficiency symptoms
addisons disease
chronic fatigue !
abdominal pain, N/V,
postural hypotension
hyperpigmentation of the skin
why is skin hyperpigmentation seen in addisons disease
a feedback loop increases melanin synthesis
low cortisol drives increased production of POMC causing increased ACTH and increased melanocyte stimulating hormone
is hyper pigmentation seen in secondary adrenocortical insuficiency
no
what are the common causes of chronic primary adrenocortical insufficiency
autoimmune adrenalitis
infections
metastatic neoplasms
congenital
what is autoimmune adrenalitis
what are the mutations
the most common cause of primary chronic adrenocortical insuffciency that has a mutation in AIRE genes
APS1- fungal infections, teeth abnormalities, other autoimmune diseases like hypoparathyroidism
APS2- autoummune thyroiditis
APS-1 mutations also cause
hypoparathyroidism and fungal infections
adrenal isuf. too
APS-2 mutations also cause
autoimmune thyroiditis
adrenal insuf. too
what does autoimmune adrenalitis look like on histology
lymphocytic infiltrate actively attacking the adrenal glands
what infection can cause primary chronic adrenocortical insufficiency
tuberculosis showing caseous necrosis (cheesy) in the adrenal gland
congenital adrenal insufficiency can also casue chronic primary adrenocortical insufficency what are the two types
adrenoleukodystrophy and adrenal hypoplasia
what is adrenoleukodystrophy
the accumulationof very long chain fatty acids that cannot be brolen down and settle in the brain, nervous system, and adrenal gland
it is x linked and leads to learning diabilities, sezuires, adrenal insufficiency, and skin hyperpigmentation
what is congential adrenal hypoplasia
a genetic cause of chronic primary adrenocortical insuffiency that is from an underdeveloped adrenal cortex
what is secondary adrenocortical insufficiency
adrenal insuffiency due to ACTH secretion def in the pituitary
what is tertiary adrenocortical insufficiency
low cortisol due to def in CRH secretion
what is the major difference in secondary and teritary adrenocortical insufficiency in comparision to primary insufficiency
there is no hyperpigmentation
adrenal carcinomas are typically _ (small/large) and poorly circumscribed there is necrosis and hemorrhage and _ confirms malignancy
large
metastasis or local invasion
poor prognosis -2 years
what are adrenal incidentalomas
an adrenal mass larger than 1cm that comes to attention on workup
asymptomatic
if they are not causing any problems just repeat imaging
rule out cushing syndrome, pheochromocytoma etc.
any alarming features shuold be worked up
what is an adrenal myelolipoma
this is a benign lesion that consists of mature fate and hematopoientic elements
trilineage- erythrocytes, myeloid, megakarycytes
grossly: yellow fat with dark hematopoetic areas
what is a pheochromocytoma
this is a tumor of the adrenal medulla chromaffin cells
it secretes catecholamines
what are the sympotms of a pheochromocytoma
elevated blood pressure
abrupt elevations in blood pressure with the sudden release of catecholamines
increased HR, sweating, headache, diaphoresis, palpitations, anxiety
how do you test for pheochromocytoma?
urinary or plasma metanephrines which will be elevated in disease
what is the pathophysiology of a pheochrmocytoma
release of catecholamines
epinephrine acts on beta 2 receptors and increases cardiac output
norepineprhine works on alpha 1 receptors and increases cardiac output and constricts blood vessels
causes hypertension
what is the rule of 10s for a pheochromocytoma
10% are extra-adrenal
10% of sporadic tumors are bilateral
10% are malignant
10% do not show hypertension
25% show familal mutations
gross apperance of pheochromocytoma
well circumscribed, yellow/tan
histology of pheochromocytoma
discrete nests of supporting sustentacular cells called zellballen
endoctine atypia (doesnt mean malignancy)
