Adrenal Disorder Flashcards
Adrenal Anatomy
zones of the adrena gland & hormones thye secrete
Adrenal Glands
- sit on top of the kidneys
- outer part: cortex (3 layers)
- inner part: medulla
Cortex
- Glomerulosa : aldosterone secreted from here (stimulated by RAAS system)
- Fasciculata: cortiosl and androgens secreted here (stimulated by ACTH from pituitary, CRH from hypothamlus)
- Reticularis: cortisol and androgens secreted here (stimulated by ATCH from pituitary and CRH from hypothamlus)
Medualla
- release epinephrine and norepinephrine as stimulated from nervous system (sympatheic, autonomic nerves)
- “fight/flight” response
- major location of epinephrine production
- these bind (the EPi) to alpha and beta receptors throught the body
Zona Glomerulosa
- RAAS triggers this to secretes aldosterone: whcih goes to kidneys and reuptakes sodium and secretes potssium
- this is the only area where aldosterone is secreted and NO steroid and androgens are secreted
- BECAUSE there is no 17-alpha hydrolyxase enzyme within these cells
Zona Fasciculata
- thickest portion producing both cortisol and androgens
- because this are DOES have 17-alpah hydroxylase enzyme to convert
- stimulated by ACTH
Zona Reticularis
- smaller amount, but does still release cortisol and androgens in the simulation of ACTH
what is the HPA Axis in relation ot the adrenal glands
What does cortisol do within the body normally
Hypothalmus - secretes CRH: cortioctropin releasing hormone
CRH stimulates the pituitary to release ACTH
ACTH stimulates the adrenal glands (fasciulata and reticularis) to secrete cortisol
Cortisolremember its effects by remembering the side effects of steroids
- binds to basically every cell type in the body
- immune suppression: but also increases number of intraascular neutrophils with a relative leukocytosis
- increased gluconeogeneisis from the liver
- induces lipolysis (breakdown) in adipose tissue
- inhibits glucose uptake into muscles
- inhibits fibroblasts: drops collagen and thins skin & creates stria
- inhibits RANKL pathway and therefore stops bone formation
- alters intestinal calcium absoprtion
What is the normal Cortisol rhythm within the body
cortisol has a circadisn rhythm = levels will decrease overnight and peak in the morning
- largest secretion of cortisol occurs between 6-8 hours of sleep (3-8am) and the highest amt measure will usually be at 8am
- physicial stressors (stress, illness, anxiety, CNS issues, liver disease, alcoholism) can all impact (usually increase) cortisol levels
Adrenal Insufficiency (AI)
Etiology (two kinds)
how those differ in terms of labs (ACTH and cortisol and aldosterone)
Other causes
Etiology
- a state of which cortisol and/or mineralocorticoids (aldosterone) is NOT produced
- can be primary= the adrenal gland is the issue
(primary will show decreased cortisol + aldosterone with an increased in ACTH (trying to tell adrenals to increase)
- can be secondary = the pituitary gland is the issue
(will see decrease cortisol but NO impact on aldosterone, decreased ACTH) b/c the problem isnt the adrenal gland here, so aldosoteron can be trigger by RAAS and still work just fine; the issue here is the pituitary and ACTH!
- most comonly: the cause is primary, auto-immune insuffiency called Addison’s Disease
Other Causes
- metastatic malignancy that infilterates the gland
- infection (TB, CMB, fungi, HIV)
- infilterative (hemochrom, amyloid)
- CAH (congenital)
- drugs (-azoles)
- hemorrhage of adrenal gland
Addison’s Disease
Etiology
Symptoms
Lab Changes
Etiology
- a primary adrenal insufficiency due to auto-immune destruction of the adrenal cortex
- leading to a decrease in cortisol and a decrease in aldosterone
- assocaited with HLA-related, DM-1, vitaligo, celiac etc.
- develop with the adrenal cortexs both have been 90% destroyed will symptoms be evident
- this can be a slow onset, but also if there is an cute stressor (infection, surgery) which triggers the need for more cortisol; this can create a downward spiarl into severe adrenal crisis
so overtime, you get decreased cortisol, and teh pituitary tries to respond and incread ACTH levels
Symptoms
- hyperkalemia, hypovolemia, hyponatremia (aldosteron lack)
- weakness, fatigue, weightloss
- hyperpigmentation of the skin because the ACTH is being made from the POMC gene which also makes melanin precurser (seen earliest on the gums)
- hypotension!!!
- GI disturbances, abd. pain
- Salt Craving (becuase low)
- postural hypoten.
Lab Changes
- hypovolemia, hyponatremia
- hyperkalemia
- hypoglycemia
- high ACTH
- low cortisol (LOW at AM cortisol levels when they should be high)
- low aldosterone
- can see eosinophilia and lymphocytosis (slight)
what is an Adrenal Crisis
- a state of ACUTE AI
- think about it as exposed to trauma, infection, surgery, dehydration, vomiting, etc.
- present with hypotension and shock, fever, dehydartion, volume depletion
can occur for those with AI who are undiagnosed, not manageed or were pre-op treated
ususally due tot the lack of aldosterone
Adrenal Insuffiency (Addisons)
Diagnosis
screening test of choice will be an AM cortisol
- we would expect normal to be high; in AI they doent have enought cortiosl so its LOW ( < 3mcg/dl)
if AM cort. is LOW = move onto an ACTH stimulation test
(theoretically: if normal wokring adrenal gland: when given ACTH: should stimulate the production of cortisol, in AI there will be no increase in cortisol because the adrenal gland is damaged)
give exogenous cACTH (Cosyntropin) IV and check cortsiol before and 60 mins. later
- if cortisol > 18 = or changes/increases by 8 - NOT AI
- if no change, fail to spike = diagnosis of AI
a normal stim test will not rule out secondary causes!!! because the problem may be with the pituitary
Adrenal Insuffiency (AI) - Addisions
Treatment
Acute adrenal Crisis : IV steroids Dextamethasone, hydrocortisone with IVfluids
- replacing the aldosterone acutely wont help: but later on want to replace with fludracortisone
Chronic AI: pt. must be on stroids and mineralocorticoid
- Hydrocortisone (best option) because can dose am and pm differntly
- also prednisone, dextameth
- Mineralocorticoid: Fludracortisone (floref) (titrate)
Stress Dosing: for AI pts. in the setting of illness, N/V, physical stress –> they should DOUBLE the dose and aggressively rehydrate
- pre-op they usually are put on IV steroids during to prevent crisis then taper down
Secondary Adrenal Insuffiency
Etiology (most commonly from?)
Labs
Diagnosis
secondary = not at the level of teh adrenal gland but due to other pathology
- most commonly: this is due to chronic steroid use: exogenous steroids tell the adrenal gland “ i dont need to work” and it shuts off
- other causes: organic pituitary diseases causing hypopituitary (low ACTH)
Labs
- LOW ATCH
- LOW cortisol
WILL NOT BE BRONZE: bronze only happens with increase ACTH production
Diagnosis
- ACTCH stimulation test cannot rbe used to rule this out
- insulin induced hypoglycemia: give insulin: low glucose: trigger cortisol to increase glucose in blood
- if no cortisol: wnt be able to increase glucose lelve
Congenital Adrenal Hyperplasia (CAH)
Etiology
Symptoms (classic and non-classic)
Etiology
- an autosomal recessive disorder which results in the lack of the ability to produce an enzyme necessary to produce cortiosl and aldosterone with increased hyperplasia of the adrenal cortex
- most common form is a loss of 21-hydroxalyase (90%)
- lacking 21-hydrox. means the pt. cant produce cortisol, leads to elevated ACTH and low cortisol
- with no 21-hydrox. cortisol cant be made, and neither can aldosterone – thus all the ACTH gets funneled to the androgens!!!!
Classic Symptoms
- imparied cortiosl with increased androgens
- clitoromegaly, masculinization of genitialia
- men: magrogenitosmia
- most will also have low aldosteron (hyponatermi, volemia and increase potassium)
- can progress to BMD and infertilitiy
Non-Classic Symptoms
- only mild reductions in 21-hydrox. so devlopement of the disease becomes prominent later in life
- Females: normal at birth; premature pubic hair, menstrual irregularities, hirsutism, PCOS, rapid growth
- Males: normal at birth; premature pubic hair, muscular development, bone agge and grwht
- will NOT (usually) have aldosteron issues ebeacuse theres enough 21-hydrox.
CAH: congenital adrenal hyperplasia
Labs
Treatment
Labs
- elevated 12OH progesterone because this is the step right before 21-hydrox. is used!! so if no hydro = this will build up!!!!
- androgen labs to see increased levels
- BMP
- AM cortisol (will be low)
Treatment
Classic
- if they have the aldosterone dief. = give steroids + mineralocorticoid
- if no mineralocorticoid def. = just give steroids
NOn-Classic
- give steroids
want to suppress ACTH secrepti, help with aldosterone losses
monitor….
- 12OH progesterone, renin levels, BP, BMP, skeleton
Cushings Syndrome
Etiology (Classifications)
Etiology
- an increase in cortisol due to a variety of different pathways
ACTH Dependent Cushings: an increased in ACTH causes an increase in cortisol
- Cushing Disease: which is a result of an ACTH secreting tumor
- ectopic neoplasm secreting ACTH (small cell carcinoma of lung)
ACTH -Independent: low ACTH (in response to) increased cortisol (triggered by another reason for increase cortisol)
- iatrogenic: exogenous cortiosl (steroids)
- adrenal neoplasms: secreting cortiosl wihtout an ACTH stimulus
Pseudo-Cushings: just elevated cortisol in the presence of depression, alcoholism due to chronic stess
Cushings Syndrome
symptoms and signs
Symptoms
- obesity: central
- moon facies
- supraclavicular fat pad
- buffalo hump
- HTN!! increased cortisol, constriction and obestiy caused
Skin
- thinning skin on face
- easy brusing
- purple thick striae
- acen
- fungal infection (tinea, candidiasis)
- hirsutism
- bone mineral density changes: osteopenia, osteoperosis (the breakdown due to increased cortisol)
Gonadal
- elevated androgens/cortisol (leads to suppressed triggers from the pituitary)
- amenorrhea and hypogonadism in men
Psychological
- labial (up/down) mood
- anxiety
- depression
- poor concentration
Muscles
- proximal muscle weakness
visual changes onl if its cushings disease and therefore theres an adenoma on th epituitary impacting the optic chiasm
Cushings Syndrome
Diagnosis
at least 2+ tests
first: confirm the presence of hypercortisolemia
- 1mg dextamethasne + check the AM cortisol level; giving dextamethasone should “turn off” the cortisol response aka normal people will have LOW cortisol then in the morning with this
- in cushings though, the cortisol response is “immune” and therefore will contnue to produce cortisol
- could have high fasle postivies (not a bad thing since you have to do further testing)
or
- 24 hours urine cortisol (highly sensitive/specific)
if you confirm hypercortisolemia = need to check ACTH levels (if high or not)
- if the ACTH is high : think cushing disease (aka pituitary ACTH tumor) and get brain MRI
- if ACTH is low: think adrenal neoplasm thats secreting cortisol on its own, check CT/MRI ab/pelvis
Cushing’s Disease
Etiology and Patho
Workup and Treatment
Etiology
- the most common cause of cushing syndrome
- due to an ACTH prodcing adenoma creating hypercortisolemia
- these are usually microadenomas
- completely disregard the normal circadian rhythm of cortisol release : thus NEVER EVER send an AM cortisol level, it will always been high…… with everyone……
Workup
- confirm with hypercortisolemia (dextameth test or 24 hour urine) and ACTH testing + MRI of brain to confirm
Treatment
- surgical: transsphenoid resection of teh ACTH adenoma
- radiotherapy: can be used for those with persistant disease after resection
rarely….
- metyrapone
- ketoconazole
- mitotane
