Adrenal Pathology Flashcards
How many adrenal glands do we have?
two - at the upper poles of the kidneys
What are the two separates parts of the adrenal glands?
cortex (three zones) and medulla
What are the three zonas of the cortex?
zona glomerulosa
zona fasciculata
zona reticularis
What does the zona glomerulosa secrete? THe outside part….
mineralocorticoids
What does the zona fasciculata secrete? The middle part….
glucocorticoids
What does the zona reticularis secrete? The inside part….
sex hormones
What does the medulla secrete?
epinephrine and norepinephrine
What are the three disorders that arrise from too much adrenal hormone?
Cushing syndrome (too much cortisol) Hyperaldosteronism (too much aldosterone) Adrenogenital syndrome (too much catecholamines?)
What is the mnemonic for what cortisol does?
cortisol is BBIIG
maintains Blood pressure breaks down Bone suppresses Inflammation suppresses Immune system stimualtes Gluconeogenesis
What are the symptoms of cushing syndrome?
hypertension weight gain characteristic habitus weakness glucose intolerance thin skin osteoporosis infeciton mental changes hirsutism menstrual abnormalities
What lab tests do you use for diagnosis of Cushing’s syndrome?
24 hour urine free cortisol
loss of normal diurnal cortisol secretion
What two tests do you use to determine the cause of the cushing syndrome?
ACTH level (tells you if the issue is with the pituitary)
Dexamethasone suppression test
What is the most common cause of cushing syndrome?
Iatrogenic! Taking steroids
What will lab tests show in iatrogenic cushing syndrome?
increased cortisol (with no Dexa supression)
decreased ACTH (the prednisone does feedback inhibition on the pituitary)
What causes cushing DISEASE?
pituitary cushing syndrome - a tumor in the atnerior pituitary makes too much ACTH
What will happen to the adrenal cortices in pituitary cushing syndrome (cushing disease)?
they will become hyperplastic
What will lab tests show in pituitary cushing syndrome?
increased cortisol (with dexa suppression) (note this is surprising, but pituitary adenomas can be turned off with high dose dexa)
increased ACTH
Is the adrenal cortex hypoplastic or hyperplastic in ADRENAL cushing syndrome?
can be either
What will lab tests show in adrenal cushing syndrome?
increased cortisol (with no dexa suppression)
decreased ACTH
What lung cancer will cause paraneoplastic cuhshing syndrome?
small-cell
Will the adrenal cortices be hypoplastic or hyperplastic in paraneoplastic cushings?
hyperplastic because of all the fake ACTH stimulation
What will lab tests show in paraneoplastic cushing syndrome
increased cortisol (with no Dexa suppression)
increased “fake” ACTH because the test can’t differentiate true ACTH from the cancer’s ACTH
Back to CRRAB…How is the release of aldosterone triggered?
angiotensinogen is converted to angiotensin 1 by renin
Ang 1 is converted to Ang II by ACE
Angiotensin II then triggers the release of aldosterone
So increased renin leads to ___ aldosterone
increased
What does aldosterone do?
- retain Na and water
- pee out K
so hypernatremia, increased BP and hypokalemia
What will hypertension do to aldosterone levels?
decresas renin, so decreased aldosterone
hence, you pee out Na and H20 and retain K, leading to hyponatremia, decreased BP and hyperkalemia
What is the general cause of primary hyperaldosteronism? Two specific causes?
you have increased aldosterone release, leading to decreased renin via feedback
caused by a cortical adenoma or cortical hyperplasia
What syndrome is associated with cortical adenoma?
Conn syndrome
What are the main symptoms of primary hyperaldosteronism?
hypertension (hypernatremia)
weakness
fatigue
psychosis (hypokalemia)
What will the lab findings be in primary hyperaldosteronism?
elevated aldosterone low renin hypernatremia hypokalemia metabolic alkalosis (loss of H+ along with the K+)
What is the general cause of secondary hyperaldosteronism?
abnormally increased renin
What are three causes of the abnormally increased renin that leads to secondary hyperaldosteronism?
CHF
decreased renal blood flow (like in RAS)
renin-producing tumors
What are the symptoms of secondary hyperaldosteronism?
same as primary….
hypertension (hypernatremia)
weakness, fatigue and psychosis (hypokalemia)
What will the lab findings be in secondary hyperaldosteronism?
elevated aldosterone high renin hypernatremia hypokalemia metabolic alkalosis (loss of H along with K)
What makes these lab findings different from primary hyperaldosteronism?
high renin
What are the two general cuases of virilization?
- primary gonadal disorders
2. primary adrenal disorders
What are the two general primary adrenal disorders?
adrenocortical neoplasms
congenital adrenal hyperplasia
Adrenocortical carcinoma is super rare, but how does it present?
you get sudden virilization in a girl or woman
sometimes has a palpable abdominal mass
Does an adrenocortical carcinoma have a good or gad prognosis?
bad
What’s wrong in congenital adrenal hyperplasia?
the patient has a deficiency in an enzyme in volved in making either/or the minerlocorticoids of the glucocorticoids, which means you 1. lose the feedback inhibition on the pituitary and 2. have all the hormone precursors being shunted into the sex steroid synthesis pathway
this means they have low aldosteron, low cortisol (with all those symptoms) and high testosterone leading to virilization
What is the most common enzyme deficiency that leads to congenital adrenal hyperplasia?
21 hydroxylase deficiency, which is required for both cortisol and aldosterone synthesis
What are the three types of 21 hydroxylase CAH?
- salt-wasting (wher eyou get no aldosterone whatsoever)
- simple virilizing (some aldosterone)
- laste-onset virilizing some aldosteron and some cortisol)
all depends on how much active enzyme you have
So in congenital adrenal hyperplasia, which layer of the cortex will be big?
the zona reticularis (wince that’s what makes the sex steroids(
What are the two general kinds of primary adrenal insufficiency?
acute or chronic
What is the more common name for primary chronic adrenal insufficiency?
Addison disease
What is Addison’s disease?
typically an autoimmune destruction of the adrenal cortex such that the patient cannot make cortisol and mineralocorticoids
What are the main symptoms of addison’s disease?
weakness, fatiuge, GI complains
hypotension (no aldosterone)
skin hyperpigmentation
Why do you get the skin hyperpigmentation in addisons?
You don’t have cortisol or aldosteron feeding back to inhibit the pituitary, so the pituitary just keeps making a ton of ACTH
remember that ACTH is derived from POMC. Remember that melanocyte stimulating factor is also derived from POMC, so you get lots of melanocyte stimulation leading to a bronzing effect
What is the management for an acute exacerbation of addison’s?
IV Na+ (bc they’re hyponatremic due to lack of aldosterone)
hydrocortisone (since they can’t make cortisol)
dextrose
What does Addison’s disease look like on histology?
you see very little cortex left and what is there will be filled with lymphocytes
Although Addison’s can present in an acute-like manner, it’s really a chronic problem. What are the two most common causes of actual primary acute adrenal insufficiency?
- rapid steroid withdrawal (because their adrenal glands have hypertrophied)
- Massive adrenal hemorrhage
What is the classic setting for massive adrenal hemorrhage and what is the syndrome called?
waterhouse-friderichsen syndrome
A young child with a N. meningitidis infection presenting in DIC with hypotension and shock
they just get massive bilateral adrenal hemorrhage which rapidly progresses. Often fatal
What is secondary adrenal insufficiency typically caused by?
pituitary or hypothalamic insufficiency related to tumor, infection, radiation or infarction
What are the clinical features of secondary adrenal insufficiency?
you have decreased ACTH, so you have decreased adrenal products
you get the symptoms of decreased cortisol and decreased sex steroids
Why will mineralocorticoids be normal in secondary adrenal insufficiency?
because the renin axis is intact, so the signal for aldosteron release is still there
Why don’t you have the hyperpigmentation in secondary adrenal insufficiency?
beause the issue is with too little ACTH. If you have no ACTH, then you’re probably not making melanocyte stimulating factor either
There are two tumors of the adrenal medulla. What are they?
- pheochromocytoma
2. neuroblastoma
What is a pheochromocytoma a neoplasm of?
catecholamine-producing cells in the medulla
What are the symptoms of pheochromocytoma?
episodic in nature…
pressure (HTN) pain (headache) perspiration palpitations (tachycardia) pallor
What labs can you do to diagnose a pheochromocytom?
urine analysis for catecholamien break-down products like VMA and metanephrines
Why is a pheochromocytoma called the 10% tumor?
10% are extra-adrenal (paragangliomas) 10% are bilateral 10% are familial 10% are malignant 10% of patients don't have HTN
What does a pheochromocytoma look like under histology?
littles that hang out in ball-like packets called zellballen
What kind of cells is a neuroblastoma derived from?
neural crest
Neuroblastoma presents in what stage of life?
childhood
True or false: prognosis for neuroblastoma is better in children over 18 months of age
false - better for children less than 18 months
True or false: prognosis is better for hyperdiploid tumors
true (whichi s unusual)
Prognosis is better if the tumor has fewer copies of what tumor promoter gene?
N-myc
True or false: in really young children, some neuroblastoma (even metastatic) can go away with time.
true!
What does neuroblastoma look like micrscopically
it’s in the calss of small round blue cell tumors
so it has small round blue cells arranged in homer-wright rosettes
WHat is in the center of a homer-wright rosette?
neuropil
